• The goals of treatment in the acute phase are to:
  • Rapidly reduce the inflammation in the coronary arteries
  • Minimize the incidence & progression of coronary artery aneurysm
  • Prevent arterial thrombosis

• Long-term therapy in individuals who develop coronary artery aneurysm is aimed at preventing myocardial ischemia or infarction

Primary Disease

• Treatment of intravenous immunoglobulin (IVIG) & Aspirin is given w/in the 7th-10th day of onset of illness
  • The treatment regimen has an overall systemic anti-inflammatory effect in approximately 80% of patients & reduces the formation of aneurysm to<5%
  • Treatment should be initiated once coronary artery aneurysm is detected in a patient prior to fulfilling all the diagnostic criteria

Intravenous Immunoglobulin (IVIG)

• Efficacy of intravenous immunoglobulin (IVIG) administered in the acute phase in reducing the prevalence of coronary artery abnormalities is well established
• It also reduces the inflammation of the vessel walls involved by the disease
• It is recommended that intravenous immunoglobulin (IVIG) be administered in Kawasaki Disease patients before the 10th day of illness, either having persistent fever of unknown origin/cause, or significant elevation of  erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) & serum amyloid-A (SAA)
• Intravenous immunoglobulin (IVIG) should not be administered in patients in whom the diagnosis of Kawasaki disease has been missed earlier or if it occurred retrospectively w/o persisting lab findings of inflammation

Aspirin

• Used to reduce inflammation & to inhibit platelet aggregation; however, it does not lower the frequency of the development of coronary abnormalities
• Recommended dose: 30-100 mg/kg/day, until normalization of inflammatory markers, specifically  C-reactive protein (CRP)
• After the acute phase, dose can be reduced to a single daily dose of 3-5 mg/kg; continue the dose for at least 6-8 weeks or longer if echocardiography shows coronary changes
• High-dose Aspirin is aimed at reducing fever & inflammatory signs related to Kawasaki disease
• Low-dose Aspirin in the subacute phase is aimed at reducing the risk of thrombosis in patients showing coronary artery dilations

Flurbiprofen

• A potential alternative to Aspirin in patients w/ severe hepatic impairment
• Further studies are needed to establish its efficacy on acute Kawasaki disease

Clopidogrel

• May be a potential alternative to patients w/ an allergy to Aspirin or w/ concomitant varicella & influenza infection
• Efficacy & safety have not been established in children

Corticosteroids

• Usefulness in the initial treatment of Kawasaki disease is not well established
• A recent study showed that there is a high regression rate of coronary artery aneurysm, including giant aneurysms, after intravenous immunoglobulin (IVIG) infusion followed by pulse IV Methylprednisolone at a dose of 30 mg/kg for 3 consecutive days

Pentoxifylline

• Therapeutic adjunct to standard therapy
  • Inhibits tumor necrosis factor-α (TNF-α ) & messenger ribonucleic acid (mRNA) transcription

• Role as part of initial treatment in Kawasaki Disease is uncertain

Refractory Kawasaki Disease

Intravenous Immunoglobulin (IVIG)

• Repeat doses of intravenous immunoglobulin (IVIG) are usually given 36 hours after completion of the first dose
• Retreatment w/ 2 g/kg intravenous immunoglobulin (IVIG) is recommended; doses can be repeated for a total of 3 infusions

Corticosteroids

• Reduce fever but effects on coronary artery abnormalities are uncertain
  • High incidence of giant aneurysms & coronary artery rupture have been reported

• Treatment should be restricted in patients in whom ≥2 infusions of have been ineffective in alleviating fever & acute inflammation
• Most commonly used steroid regimen is IV Methylprednisolone 30 mg/kg 24 hourly for 3 consecutive days

Tumor Necrosis Factor (TNF) Inhibitors

• Infliximab
  • Has been shown to be successful in patients refractory to intravenous immunoglobulin (IVIG) & corticosteroids
  • Reverses the clinical signs of Kawasaki disease
  • May be used in patients w/ severe coronary artery disease, w/o any substantial side effects
  • Reduces cytokine-mediated inflammation but has no effect in suppressing vascular cellular infiltration
  • Further studies are needed to establish its effect in reducing the prevalence of coronary artery aneurysms

• Etanercept
  • Therapy has lead to defervescence w/o increase in coronary artery diameter or new coronary artery dilation
  • Further studies are needed to establish its use in the treatment of Kawasaki disease

• Ulinastatin
  • A human urinary glycoprotein proteolytic enzyme inhibitor that suppresses production & down-regulates various cytokines involved in the inflammatory process
  • Indicated for patients resistant to intravenous immunoglobulin (IVIG) treatment
  • Studies have shown that patients treated w/ intravenous immunoglobulin (IVIG), Ulinastatin & Aspirin combination therapy did not require further treatment & had lower risk of developing coronary artery aneurysm

Immunosuppressants

• Eg Cyclosporin A, Methotrexate
• May be used in patients refractory to intravenous immunoglobulin (IVIG) therapy as 3rd-line treatment
• Studies have shown that treatment w/ Cyclosporin A effectively reduces fever

• Management depends on severity & extent of coronary involvement
• Platelet activation is a profound component of the acute illness & persists throughout the convalescence & chronic phases
• Patients including those w/o coronary sequelae, should be treated w/ antiplatelet drugs at low doses for about 3 months
  • Platelet aggregation activity remains high during the 1st 3 months after onset

• Patients should be carefully monitored for bleeding tendency due to excessive anticoagulant therapy

Aspirin

• Low-dose Aspirin may be appropriate for asymptomatic patients w/ mild & stable coronary disease
• As the extent & severity of coronary enlargement increases, combination w/ other antiplatelet agents may be more effective in suppressing platelet aggregation
• Combination of Aspirin & Dipyridamole is used to treat patients w/ mild-to-moderate coronaryw involvement

Clopidogrel

• Combination of Clopidogrel & Aspirin has been shown to be more effective than either agent alone in preventing vascular events in both coronary & cerebral arteries in adults

Dipyridamole

• Effectively potentiates the effects of Aspirin in inhibiting platelet aggregation
• Not to be given alone; may cause hemorrhage & worsening of angina

Ticlopidine

• Given in combination w/ Aspirin to prevent coronary ischemia & thrombus formation

Heparin

• The use of low molecular weight heparin w/ Aspirin has been advocated in rapidly expanding coronary aneurysms since the risk of thrombosis or bleeding is high

Warfarin

• Combination of Warfarin & Aspirin is used to prevent thromboembolism, myocardial infarction (MI) & potential risk of sudden death in patients w/ giant coronary aneurysms

Treatment of Coronary Thrombosis

• Goals of therapy include reestablishing coronary patency, myocardial salvaging & improving patient survival
• Should target multiple steps in the coagulation cascade
• The following agents may be administered to infants & children w/ coronary thrombosis w/ varying success rates: Alteplase, Monteplase, Streptokinase, Urokinase, tissue plasminogen activator (tPA)

Treatment of Myocardial Ischemia

• Treatment is aimed at increasing coronary blood flow, preventing or relieving coronary spasm, inhibiting the formation of thrombi & decreasing cardiac work