Infants, older patients with Kawasaki disease demonstrate different complication risks
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The risks for unresponsiveness to intravenous immunoglobulin and the development of coronary artery abnormalities differ between infants and older patients with Kawasaki disease, according to data published in JAMA Network Open.
The researchers added that providers should address residual risk factors for Kawasaki disease-related coronary artery abnormalities other than initial unresponsiveness to IVIG, especially in infants.
“Kawasaki disease is often complicated by coronary artery abnormalities (CAAs), and approximately 15% to 25% of untreated children develop coronary artery aneurysms,” Nobuhito Takekoshi, MD, of the Wakayama Medical University school of medicine, in Wakayama, Japan, and co-authors wrote. “Kawasaki disease is currently the most common cause of pediatric-acquired heart disease in developed countries.
“Intravenous immunoglobulin (IVIG) is the primary therapy for [Kawasaki disease (KD)] and has been shown to reduce the incidence of CAAs,” they added. “However, approximately 20% of patients with KD do not respond to the initial IVIG treatment and receive additional IVIG treatments and/or other therapies. ... In addition, previous epidemiologic studies have reported that a younger or older age and male sex are associated with the development of CAAs in patients with acute-phase KD. ... To our knowledge, few studies have focused on the association of age at the onset of KD and patient sex with refractory KD.”
To determine whether there are different risk factors for initial unresponsiveness to IVIG and CAA development in patients with Kawasaki disease, Takekoshi and colleagues conducted a retrospective cohort study. The researchers created a database of patients with Kawasaki disease from across the Wakayama prefecture. The analysis included 2,414 patients identified between Oct. 1, 1999, and Sept. 30, 2019, with data analysis conducted in March. To be eligible, patients were required to have been diagnosed with Kawasaki disease by a certified pediatrician based on criteria established by the Japan Kawasaki disease Research Committee.
The primary outcome was the presence or absence of “optional or additional” therapies. According to the researchers, the presence of additional therapies indicated that the patient was unresponsive to IVIG. Additionally, researchers evaluated the presence or absence of CAASs using criteria put forth by the Japanese Ministry of Health. CAAs were defined as aneurisms of “giant,” “medium” or “small” dilation, clear irregularity in the lumen and larger-than-normal internal diameters.
In all, 2,414 patients were included in the analysis. Of those, 535, or 22.2%, received optional or advanced treatments. Additionally, 68 patients (2.8%), developed CAAs 1 month after disease onset. In a sex-adjusted analysis, patients aged younger than 12 months demonstrated an OR of 0.77 (95% CI, 0.59-0.99) for being unresponsive to IVIG. In the same group, the OR for developing CAAs was 1.94 (95% CI, 1.07-3.52). Among those older than 47 months, patients were more likely to be unresponsive to IVIG (OR = 1.32; 95% CI, 1.05-1.67) and develop CAAs (OR = 2.47; 95% CI, 1.39-4.39).
Meanwhile, girls aged younger than 12 months demonstrated ORs of 1.02 (95% CI, 0.65-1.60) for IVIG unresponsiveness and 3.79 for CAA development (95% CI, 1.21-11.9).
“This cohort study identified a difference in risk factors between initial unresponsiveness to IVIG and the development of CAAs among infant patients with KD,” Takekoshi and colleagues wrote. “Among vulnerable patients with KD, latent risk factors not associated with being refractory to initial IVIG treatment may exist for developing CAAs. Therefore, the residual risks and the initial unresponsiveness to IVIG must be addressed to prevent CAA complications among patients with KD.”
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