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.

Galectin-3 (Gal-3) is a multifunctional matricellular protein associated with heart failure and cardiovascular events. Gal-3 is required for transforming growth factor-β pathway-mediated myofibroblast activation that is a key process in coronary artery aneurysm formation in Kawasaki Disease (KD). Autopsies from young adults late after KD onset (AKD) have demonstrated bridging fibrosis throughout the myocardium and arteries. In this study, we postulated that Gal-3 may participate in the pathogenesis of myocardial and vascular fibrosis and the remodeling of coronary artery aneurysms following acute KD.We measured plasma Gal-3 levels in 63 pediatric KD (PKD) and 81 AKD subjects. AKD subjects with giant aneurysms had significantly higher Gal-3 levels compared to the other adult groups (all p<0.05). All PKD groups had significantly higher Gal-3 levels than pediatric healthy controls (HC) (all p<0.05). Histological and immunohistochemical staining was performed on tissues from 10 KD autopsies and one explanted heart. Gal-3 positive staining was detected associated with acute inflammation and in spindle-shaped cells in the myocardium and arterial wall in KD subjects with giant aneurysms.AKD subjects with giant aneurysms and PKD subjects had significantly higher plasma Gal-3 levels than HC and Gal-3 expression was increased in the myocardium of KD subjects who died with either acute inflammation or marked myocardial fibrosis. Gal-3 may be a clinically useful biomarker that identifies a subset of KD patients at highest risk of myocardial and vascular fibrosis, and may be an attractive therapeutic target to prevent myocardial dysfunction in this subset.

Objective: To characterize the clinical presentation and outcomes of Kawasaki disease (KD) in infants <6 months of age as compared to those ≥6 months in Latin America. Methods: We evaluated 36 infants <6 months old and 940 infants ≥6 months old diagnosed with KD in Latin America. We compared differences in laboratory data, clinical presentation, treatment response, and coronary artery outcomes between the two cohorts. Results: The majority (78.1%) of infants and children ≥6 months of age were initially diagnosed with KD, as compared to only 38.2% of infants <6 months. Clinical features of KD were more commonly observed in the older cohort: oral changes (92 vs. 75%, P = 0.0023), extremity changes (74.6 vs. 57.1%, P = 0.029), and cervical lymphadenopathy (67.6 vs. 37.1%, P = 0.0004). Whether treated in the first 10 days of illness or after the 10th day, infants <6 months were at greater risk of developing a coronary artery aneurysm compared to KD patients ≥6 months treated at the same point in the course of illness [ ≤ 10 days (53.8 vs. 9.4%, P = 0.00012); >10 days (50 vs. 7.4%, P = 0.043)]. Conclusion: Our data show that despite treatment in the first 10 days of illness, infants <6 months of age in Latin America have a higher risk of developing a coronary artery aneurysm. Delay in the diagnosis leads to larger coronary artery aneurysms disproportionately in these infants. Thus, suspicion for KD should be high in this vulnerable population.