Treatment of Kawasaki Disease
Treatment of Kawasaki Disease
Abstract & Commentary
By Hal B. Jenson, MD, FAAP, Professor of Pediatrics, Tufts University School of Medicine, and Chief Academic Officer, Baystate Medical Center, Springfield, MA, is Associate Editor for Infectious Disease Alert.
Dr. Jenson is a speaker for Merck.
Synopsis: During 2001-2006, approximately 15% of children with Kawasaki disease in the United States required re-treatment, and 7% required readmission within six weeks. The use of infliximab for immunoglobulin-resistant Kawasaki disease has increased and was 2.3% in 2006.
Source: Son MBF, et al: Treatment of Kawasaki disease: Analysis of 27 US pediatric hospitals from 2001 to 2006. Pediatrics. 2009;124:1-8.
A study of immunoglobulin-resistant kawasaki disease in the United States was conducted using data from the Pediatric Health Information System. All patients diagnosed and treated for Kawasaki disease, including readmissions, were identified during 2001 to 2006 among 27 hospitals representing all geographic regions of the country.
During the study period, 4,811 patients with Kawasaki disease had 5,197 admissions. The annual incidence of Kawasaki disease increased 32.6% from 2001 (n = 678) to 2006 (n = 899). Male patients represented 60.4% of all patients. Asian patients were over-represented (p < 0.001), constituting 6.9% of patients admitted with a diagnosis of Kawasaki disease, compared with constituting 1.6% of all patients in the database. The median length of stay was three days, and did not change during the six-year study. A total of 351 patients (7.3%) required readmission within six weeks, and 31 patients (8.8% of patients who required re-admission and 0.6% of all patients) required two or more readmissions. Age < 1 year was associated with a greater likelihood of readmission (9.6% vs. 68%, p = 0.005). Readmission was not associated with gender, ethnicity, insurance type, or median length of stay of first admission.
Retreatment with intravenous immunoglobulin (IVIG) was administered to 14.8% of patients (n = 712), including 531 patients (11.0%) during their first admission and 213 (60.7%) of the 351 patients who were readmitted (32 patients were retreated with IVIG during both initial and subsequent admissions). Other anti-inflammatory therapies used for immunoglobulin-resistant Kawasaki disease included methylprednisolone (5.8%), orally administered prednisone (2.8%), and infliximab (1%). The proportions of children who received IVIG retreatment and corticosteroids remained stable during this period, and the use of infliximab increased from 0% in 2001 to 2.3% (21 of 899 patients) in 2006.
Antithrombotic therapy included aspirin in 4,429 patients (92%), warfarin in 54 patients (1.1%), enoxaparin in 49 patients (1.0%), tissue plasminogen activator in 33 patients (0.7%), clopidogrel in 16 patients (0.3%), and abciximab in 10 patients (0.2%). Unfractionated heparin was administered to 2,004 patients (41.7%), but its use for maintenance of intravenous access could not be distinguished from its use for therapeutic anticoagulation.
Coronary artery aneurysms were diagnosed in 127 patients (2.6%) during the first admission and in 157 patients (3.3%) overall. Risk factors for coronary artery aneurysms included male gender (3.8% vs. 2.4%, p = 0.006), age < 1 year (8.0% vs. 2.2%, p < 0.001), and Hispanic ethnicity (p < 0.001).
Six patients died during hospitalization, for a mortality rate of 0.12%. The ages ranged from five months to 11 years (median: 29 months); each of the six patients received one or more doses of IVIG and aspirin.
Commentary
This is the first large, multicenter report of the current treatment regimens used for Kawasaki disease in the United States. Approximately 15% of patients admitted with Kawasaki disease receive retreatment during initial or subsequent admissions.
In 2004, the American Heart Association and the American Academy of Pediatrics published recommendations for the diagnosis and treatment of Kawasaki disease (Pediatrics. 2004;114:1708-1733). IVIG (2 g/kg) and aspirin are the mainstays of initial treatment. Failure to respond is defined as persistent or recrudescent fever ≥ 36 (48) hours after completion of the initial IVIG infusion. For refractory cases, most experts recommend IVIG retreatment with a second dose of IVIG (2 g/kg). There is currently some variability in the agents used for subsequent treatment of immunoglobulin-resistant Kawasaki disease.
Elevated levels of tumor necrosis factor (TNF-α) have been reported in patients with Kawasaki disease, especially those with coronary artery abnormalities and, therefore, the use of infliximab is reasonable, especially for refractory cases. The use of infliximab (Remicade) for Kawasaki disease increased from 0% in 2001 to 2.3% in 2006. Infliximab is a chimeric monoclonal antibody that binds TNF-α and blocks attachment to TNF-α receptors on T cells, which reduces inflammatory response. When used, it is generally administered only once or, at most, twice to children with immunoglobulin-resistant Kawasaki disease. There are no controlled, prospective, clinical trials with adequate power to assess the efficacy and safety of infliximab in the management of Kawasaki disease. A multicenter trial of the safety and efficacy of infliximab vs. a second dose of IVIG for refractory Kawasaki disease is underway.
A study of immunoglobulin-resistant kawasaki disease in the United States was conducted using data from the Pediatric Health Information System. All patients diagnosed and treated for Kawasaki disease, including readmissions, were identified during 2001 to 2006 among 27 hospitals representing all geographic regions of the country.Subscribe Now for Access
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