Kawasaki Disease Medication
- Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Russell W Steele, MD more...
The goals of pharmacotherapy in Kawasaki disease are to reduce inflammation and platelet activation. Early and aggressive intervention improves outcome. Standard treatment includes intravenous immunoglobulin (IVIG) to treat inflammation and to prevent consequences of coronary artery disease. Occasionally, it is an advantage to combine IVIG with corticosteroids, such as to reduce the incidence of formation of coronary artery aneurysms.
Aspirin has traditionally been part of standard treatment. Although its value has been called into question, most experts use high-dose aspirin for a variable period, followed by lower-dose aspirin for its antiplatelet effects. Other anticoagulants or antiplatelet agents (eg, warfarin, dipyridamole) are occasionally used.
Ibuprofen antagonizes aspirin's antiplatelet activity and should be avoided.
Because these children will take aspirin for a variable period, vaccination against influenza and varicella must be ensured.
Corticosteroids have been used, typically in patients who do not respond to standard therapies. Their use in primary treatment is controversial. Treatment of IVIG-resistant Kawasaki disease with methotrexate or cyclophosphamide has been reported to be effective. Refractory Kawasaki disease with coronary aneurysms has been treated with infliximab.
Patients who are at increased risk for thrombus with significant coronary involvement have been treated with various types of medications in addition to the routine aspirin therapy. Antiplatelet medications such as clopidogrel and dipyridamole antagonize adenosine diphosphate and have a synergistic effect when given with aspirin.
Anticoagulants such as warfarin and low molecular weight heparin are used in patients with large aneurysms in whom the risk of thrombus is high. The goal is to maintain an international normalized ratio (INR) of 2-2.5.
Patients who have thrombosis and acute coronary occlusion should be treated with medical therapy because of the risk of rupture if interventional cardiac catheterization is attempted. In addition to standard treatments and warfarin, thrombolytics are given.
Because the potential exists for allergic complications with the use of streptokinase in patients who have had streptococcal pharyngitis in the last 6 months and because the triggering factor for Kawasaki disease remains uncertain, this medication is best avoided. Other drugs in this category, such as tissue plasminogen activator, tenecteplase-tissue plasminogen activator, and urokinase, may be more appropriate.
IVIG is a purified preparation of gamma globulin. It is derived from large pools of human plasma comprising 4 subclasses of antibodies, approximating the distribution of human serum.
These agents are used to improve clinical and immunologic aspects of Kawasaki disease. They may decrease autoantibody production and increase solubilization and removal of immune complexes.
IVIG is generally recommended as first-line therapy. It neutralizes circulating myelin antibodies by means of anti-idiotypic antibodies; downregulates proinflammatory cytokines, including interferon-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; and promotes remyelination. It may increase cerebrospinal fluid IgG levels (10%).
IVIG reduces the prevalence of coronary abnormalities. It leads to rapid defervescence and more rapid normalization of acute-phase reactants.
Nonsteroidal Anti-Inflammatory Agents/Salicylates (NSAIDs)
These agents inhibit prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2. Adequate anti-inflammatory therapy requires that aspirin be combined with gamma globulin. Children with coronary artery disease have received aspirin for prolonged periods.
Aspirin is used to decrease inflammation, inhibit platelet aggregation, and improve complications of venous stasis and thrombosis. It irreversibly inactivates cyclooxygenase, ultimately preventing thromboxane A2 production in platelets. Platelet function does not fully recover until new platelets are made (in 7-10 days). It is first-line therapy, along with IVIG.
Oral absorption may decrease in Kawasaki disease to < 50% (vs typical bioavailability of 85-90%). Altered bioavailability may explain why higher doses are required to achieve a salicylate serum concentration >20 mg/dL.
Antiplatelet Agents, Hematologic
Besides aspirin, dipyridamole may be used to prevent microthrombus formation.
Dipyridamole is a platelet-adhesion inhibitor that possibly inhibits red blood cell uptake of adenosine, itself an inhibitor of platelet reactivity. It may inhibit phosphodiesterase activity, leading to increased cyclic adenosine monophosphate (cAMP) levels in platelets and formation of potent platelet activator thromboxane A2.
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisolone is indicated for the treatment of steroid-responsive inflammation of the palpebral and bulbar conjunctiva, cornea, and anterior segment. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Methylprednisolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
These agents inhibit key factors that mediate immune reactions.
Infliximab may be added to treatment if steroids and other immunosuppressant drugs are ineffective in achieving or maintaining remission. Infliximab is a chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-α and inhibits its binding to the TNF-α receptor. It reduces the infiltration of inflammatory cells and TNF-α production in inflamed areas.
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