eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Kawasaki Disease: Treatment & Medication

Author: Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Private Practice
Coauthor(s): Elena L Jones, MD, Clinical Assistant Professor of Dermatology, College of Physicians and Surgeons of Columbia University; Clinic Chief, Department of Dermatology, St Luke's-Roosevelt Hospital Center
Contributor Information and Disclosures

Updated: Oct 20, 2009

Treatment

Medical Care

The main goal of treatment is to prevent coronary artery disease and to relieve symptoms. Full doses of salicylates (aspirin) and intravenous immunoglobulin (IVIG) are the mainstays of treatment. Baumer et al concluded that no quality randomized clinical trials have been performed and that current evidence is insufficient to support the use of salicylate in children with Kawasaki disease (KD) as part of their treatment regimen.14 The appropriate treatment of patients who fail to respond to IVIG remains unclear. Severe Kawasaki disease that is resistant to IVIG may benefit from intravenous pulse corticosteroid therapy or infliximab infusion. However, a recent multicenter, randomized, controlled trial did not demonstrate the efficacy of adding a pulsed dose of intravenous methylprednisolone to the conventional IVIG therapy for the primary treatment of Kawasaki disease.15

  • Admit all patients to the hospital for IVIG administration and observation until fever is controlled.
  • Closely monitor cardiovascular function.
  • Patients with small aneurysms must take aspirin.
  • Dipyridamole is indicated in patients with larger aneurysms.
  • Patients taking long-term aspirin therapy should receive an influenza vaccination to protect against Reye syndrome.

Consultations

  • Consult a pediatric or adult cardiologist for the following:
    • Children or adults with clinically significant coronary artery disease
    • Determining the appropriate timing of subsequent echocardiographic studies
    • Anticoagulation in patients with large aneurysms
    • Other studies to assess cardiac function, such as stress testing and coronary artery angiography
  • Consult a pediatric or adult infectious disease specialist to rule out infectious disease as a cause of fever.
  • Consult a pediatric or adult rheumatologist to rule out other causes of vasculitis and connective tissue diseases.
  • Consult a pediatric dermatologist to rule out other conditions that can manifest with fever and a rash.

Medication

The pathophysiology of Kawasaki disease (KD) involves inflammation. The patient's own immune system probably causes the vasculitis that leads to morbidity and mortality in Kawasaki disease. Early and aggressive intervention improves outcome. Standard treatment includes aspirin and intravenous immunoglobulin (IVIG) to treat inflammation and to prevent consequences of coronary artery disease. Other anticoagulants or antiplatelet agents (eg, warfarin, dipyridamole) are occasionally used.

Between September 2000 and March 2005, 178 children with Kawasaki disease from 12 hospitals were randomized to receive either IVIG alone or IVIG with a corticosteroid. The study concluded that the latter group had an improved clinical course and decreased coronary artery complications without an increase of unacceptable adverse effects.16

Treatment of IVIG-resistant Kawasaki disease with methotrexate has been reported to be effective.

Infliximab treatment for refractory Kawasaki disease was effective in a small study. Zulian et al found infliximab to be useful in treating patients with refractory Kawasaki disease.17 Stenbog et al also noted the effectiveness of tumor necrosis factor (TNF)-alpha blockade in patients with complicated refractory K.18

Methylprednisolone pulse therapy used to treat massive lymphadenopathy in a child with IVIG-resistant Kawasaki disease has been effective.19

Immunomodulatory agents

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.

Taniuchi et al evaluated a possible relationship between the effectiveness of gamma globulin treatment for patients with Kawasaki disease and the polymorphism of Fcgamma RIIa, IIIb, and IIIa.20 Genomic DNA was extracted from whole blood collected from 56 patients with Kawasaki disease who received gamma globulin treatment. The genotypes for Fcgamma RIIIb-NA(1, 2), Fcgamma RIIa-H/R131, and FcgammaRIIIa-F/V158 were determined to investigate the association between these polymorphisms and the development of coronary lesions.

About 23% of patients with the HH allele for the Fcgamma RIIa polymorphism developed coronary artery lesions, compared with 60% with the HR and RR alleles. HR and RR alleles may be a predictor of the progression of coronary lesions in Kawasaki disease before the start of gamma globulin therapy.

A polymorphism in plasma platelet–activating factor acetylhydrolase is involved in resistance to immunoglobulin treatment in Kawasaki disease.


Immune globulin, intravenous (Carimune, Gammagard, Gammar-P,Gamunex, Polygam S/D)

Generally recommended as first-line therapy, but not sole therapy. Neutralizes circulating myelin antibodies by means of anti-idiotypic antibodies; downregulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG levels (10%).

Adult

400 mg/kg/d IV as a single daily infusion for 4 d
Alternatively, 2 g/kg IV infused over 12 h once as single dose

Pediatric

Administer as in adults

Globulin preparation may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccine)

Documented hypersensitivity; IgA deficiency

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Flushing of the face, chills, nausea, dyspnea, and tachycardia are the most common adverse effects and typically related to infusion rate; less common adverse effects include chest tightness, dizziness, fever, headache, and diaphoresis
Check serum IgA levels before IVIG administration (use an IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d after infusion)
Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes mellitus, volume depletion, or preexisting kidney disease; laboratory findings associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

Nonsteroidal anti-inflammatory agents

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 (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

Used to decrease inflammation, inhibit platelet aggregation, and improve complications of venous stases and thrombosis. Irreversibly inactivates cyclooxygenase, ultimately preventing thromboxane A2 production in platelets. Platelet function does not fully recover until new platelets are made (7-10 d). First-line therapy with IVIG.
PO absorption may decrease in KD to <50% (vs typical bioavailability of 85-90%). Altered bioavailability may explain why higher doses required to achieve a salicylate serum concentration >20 mg/dL.

Adult

Not established for this indication

Pediatric

80-100 mg/kg/d PO divided qid for 2 wk initially; then 5-10 mg/kg PO qd for 6-8 wk until sedimentation rate and platelet count in reference range; typically used for 6-12 wk

Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs

Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; use in children (<16 y) with influenza because of association with Reye syndrome

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Pregnancy category D in third trimester; may cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, those with a history of blood coagulation defects, or those taking anticoagulants; caution in asthma; dose on borderline of that causing salicylate toxicity (monitor for toxicity [eg, vomiting, hyperpnea, lethargy, liver dysfunction]); monitor salicylate level and maintain at 18-28 mg/dL; administer influenza vaccine to protect against Reye syndrome

Antiplatelet agents

Besides aspirin, dipyridamole may be used to prevent microthrombus formation.


Dipyridamole (Persantine)

Platelet-adhesion inhibitor that possibly inhibits RBC uptake of adenosine, itself an inhibitor of platelet reactivity. May inhibit phosphodiesterase activity, leading to increased cAMP levels in platelets and formation of potent platelet activator thromboxane A2.

Adult

75-100 mg PO qid

Pediatric

Not established; limited data indicate 3-6 mg/kg/d PO divided tid

Theophylline may decrease hypotensive effects; antiplatelet activity may increase heparin toxicity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hypotension; has peripheral vasodilating effects

More on Kawasaki Disease

Overview: Kawasaki Disease
Differential Diagnoses & Workup: Kawasaki Disease
Treatment & Medication: Kawasaki Disease
Follow-up: Kawasaki Disease
Multimedia: Kawasaki Disease
References
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Further Reading

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Keywords

Kawasaki disease, KD, Kawasaki syndrome, Kawasaki's disease, KS, Kawasaki's syndrome, mucocutaneous lymph node syndrome, infantile periarteritis nodosa, myocarditis, pericarditis, pericardial effusion, mitral insufficiency, aortic insufficiency, dysrhythmias, arthritis

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Contributor Information and Disclosures

Author

Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Private Practice
Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Optigenex Consulting fee Independent contractor

Coauthor(s)

Elena L Jones, MD, Clinical Assistant Professor of Dermatology, College of Physicians and Surgeons of Columbia University; Clinic Chief, Department of Dermatology, St Luke's-Roosevelt Hospital Center
Disclosure: Nothing to disclose.

Medical Editor

Rosemary Johann-Liang, MD, Medical Officer, Infectious Diseases and Pediatrics, Division of Special Pathogens and Immunological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration
Rosemary Johann-Liang, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University
Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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