High Risk of Coronary Artery Aneurysms in Infants Younger than 6 Months of Age with Kawasaki Disease.

OBJECTIVES: To characterize the clinical presentation and outcome in infants <6 months of age with Kawasaki disease (KD) and to describe the use of newer anti-inflammatory therapies in this young population. STUDY DESIGN: We evaluated 88 infants?<6 months old and 632??6 months old treated for KD. We compared differences in laboratory data, response to treatment, and coronary artery outcomes between the 2 cohorts. Fisher exact test was used to analyze categorical variables, whereas the Wilcoxon rank sum test was used for continuous variables. RESULTS: The majority of children in both cohorts were diagnosed and treated within the first 10 days of illness (median illness day 6 in both cohorts). For patients treated within the first 10 days after fever onset, a larger proportion of infants <6 months old had a dilated or aneurysmal coronary artery on the initial echocardiogram compared with those ?6 months old (43.4% vs 19.5%). Furthermore, 18.6% of infants?<6 months old who had a normal echocardiogram at diagnosis, developed a dilated or aneurysmal coronary artery on a subsequent echocardiogram within 8 weeks of diagnosis. Twenty-eight infants?<6 months old received a single dose of infliximab without any untoward effects. CONCLUSIONS: Despite treatment in the first 10 days, infants?<6 months old with acute KD are more likely to develop coronary artery abnormalities. Thus, the development of adjunctive therapies to reduce coronary artery damage should target this population.

Coronary Artery Aneurysms in Kawasaki Disease: Risk Factors for Progressive Disease and Adverse Cardiac Events in the US Population.

BACKGROUND: The natural history of coronary artery aneurysms (CAA) after intravenous immunoglobulin (IVIG) treatment in the United States is not well described. We describe the natural history of CAA in US Kawasaki disease (KD) patients and identify factors associated with major adverse cardiac events (MACE) and CAA regression. METHODS AND RESULTS: We evaluated all KD patients with CAA at 2 centers from 1979 to 2014. Factors associated with CAA regression, maximum CA z-score over time (zMax), and MACE were analyzed. We performed a matched analysis of treatment effect on likelihood of CAA regression. Of 2860 KD patients, 500 (17%) had CAA, including 90 with CAA z-score >10. Most (91%) received IVIG within 10 days of illness, 32% received >1 IVIG, and 27% received adjunctive anti-inflammatory medications. CAA regression occurred in 75%. Lack of CAA regression and higher CAA zMax were associated with earlier era, larger CAA z-score at diagnosis, and bilateral CAA in univariate and multivariable analyses. MACE occurred in 24 (5%) patients and was associated with higher CAA z-score at diagnosis and lack of IVIG treatment. In a subset of patients (n=132) matched by age at KD and baseline CAA z-score, those receiving IVIG plus adjunctive medication had a CAA regression rate of 91% compared with 68% for the 3 other groups (IVIG alone, IVIG ≥2 doses, or IVIG ≥2 doses plus adjunctive medication). CONCLUSIONS: CAA regression occurred in 75% of patients. CAA z-score at diagnosis was highly predictive of outcomes, which may be improved by early IVIG treatment and adjunctive therapies.

Building a Natural Language Processing Tool to Identify Patients With High Clinical Suspicion for Kawasaki Disease from Emergency Department Notes.

OBJECTIVE: Delayed diagnosis of Kawasaki disease (KD) may lead to serious cardiac complications. We sought to create and test the performance of a natural language processing (NLP) tool, the KD-NLP, in the identification of emergency department (ED) patients for whom the diagnosis of KD should be considered. METHODS: We developed an NLP tool that recognizes the KD diagnostic criteria based on standard clinical terms and medical word usage using 22 pediatric ED notes augmented by Unified Medical Language System vocabulary. With high suspicion for KD defined as fever and three or more KD clinical signs, KD-NLP was applied to 253 ED notes from children ultimately diagnosed with either KD or another febrile illness. We evaluated KD-NLP performance against ED notes manually reviewed by clinicians and compared the results to a simple keyword search. RESULTS: KD-NLP identified high-suspicion patients with a sensitivity of 93.6% and specificity of 77.5% compared to notes manually reviewed by clinicians. The tool outperformed a simple keyword search (sensitivity = 41.0%; specificity = 76.3%). CONCLUSIONS: KD-NLP showed comparable performance to clinician manual chart review for identification of pediatric ED patients with a high suspicion for KD. This tool could be incorporated into the ED electronic health record system to alert providers to consider the diagnosis of KD. KD-NLP could serve as a model for decision support for other conditions in the ED.

Axillary, Oral and Rectal Routes of Temperature Measurement During Treatment of Acute Kawasaki Disease.

BACKGROUND: Important therapeutic decisions are made based on the presence or absence of fever in patients with Kawasaki disease (KD), yet no standard method or threshold exists for temperature measurement during the diagnosis and treatment of these patients. We sought to compare surface and internal (rectal or oral) routes of temperature measurement for the detection of fever as a marker of treatment resistance. METHODS: From a randomized, placebo-controlled trial of infliximab as an adjunct to primary intravenous immunoglobulin treatment for acute KD, we collected concurrent (within 5 minutes) axillary and internal temperature measurements and performed receiver-operating characteristic and Bland-Altman analyses. We also determined the ability of surface temperatures to detect treatment resistance defined by internal temperature measurements. RESULTS: Among 452 oral-axillary and 439 rectal-axillary pairs from 159 patients, mean axillary temperatures were 0.25 and 0.43 °C lower than oral and rectal temperatures and had high receiver-operating characteristic areas under curves. However, axillary temperatures ≥ 38.0 °C had limited sensitivity to detect fever defined by internal temperatures. Axillary thresholds of 37.5 and 37.2 °C provided maximal sensitivity and specificity to detect oral and rectal temperatures ≥ 38.0 °C, respectively. CONCLUSIONS: Axillary temperatures are an insensitive metric for fevers defining treatment resistance. Clinical trials should adopt temperature measurement by the oral or rectal routes for adjudication of treatment resistance in KD.

Patterns of Fever in Children After Primary Treatment for Kawasaki Disease.

BACKGROUND: We sought to determine if fever in the early postintravenous immunoglobulin (IVIG) time period (first 36 hours after IVIG completion) for Kawasaki disease, with or without additional infliximab, can predict IVIG resistance and coronary artery abnormalities (CAA). METHODS: Acute Kawasaki disease subjects enrolled in a clinical trial of infliximab plus IVIG (n = 96) versus placebo/IVIG (n = 94) had temperatures recorded every 6 hours after completion of IVIG infusion. Fever was defined as temperature >38.0°C; patients with persistent or recrudescent fever >36 hours after completion of IVIG were classified as IVIG resistant. Multivariable logistic regression by fever pattern was performed to predict outcomes (IVIG resistance and CAA). RESULTS: There was no difference in the time to defervescence between the infliximab/IVIG group (n = 96) versus placebo/IVIG group (n = 94). There was no fever after completion of IVIG in the majority of subjects [66% of those with no CAA (n = 139) and 76.5% of those with CAA, (n = 51)]. Although subjects with at least 1 fever 24-36 hours post-IVIG had a higher probability of IVIG resistance [odds ratio = 30.6 (95% confidence interval: 6.7-139.8); P < 0.0001], fever at 24-36 hours was not associated with higher likelihood of CAA. There were also 11% (n = 19) of IVIG responders who had fever at 24-36 hours post-IVIG. The majority of subjects with CAA (43 of 51, 84.3%) were identified by the initial echocardiogram, so the effect of fever on development of CAA could not be assessed. CONCLUSIONS: Fever in the first 36 hours after IVIG completion is not predictive of CAA. Our data support refraining from retreatment until 36 hours after completion of IVIG.