Refractory Kawasaki Disease with Giant Coronary Artery Aneurysms in an Infant: A Clinical Conundrum

Dear Editor,

Kawasaki disease (KD), although being the most common cause of multisystem vasculitis in childhood, is rare in infants under 6 months of age, often presenting with non-classical symptoms, thereby delaying treatment initiation, and resulting in higher rates of coronary artery (CA) abnormalities.^[1]

A 3-month-old male infant presented to the pediatric emergency department with a 10-day history of high-grade fever, irritability, rhinorrhea, watery diarrhea, and mucosal congestion of the oral cavity. Examination revealed bilateral non-exudative conjunctivitis, erythematous cracked lips, and erythema and edema of the palms and soles. Laboratory evaluation showed anemia, leukocytosis, thrombocytosis, elevated inflammatory markers, hypoalbuminemia, and sterile pyuria. Based on American Heart Association criteria, a diagnosis of complete KD was established. Baseline 2D-echocardiography on day 10 of fever (day 1 of admission) demonstrated CA dilatation with the left anterior descending (LAD) artery measuring 5.11 mm (z score: 13.7, n < 2.5), the left circumflex (LCx) artery measuring 4.47 mm (z score: 10.4, n < 2.5), and the right coronary artery (RCA) measuring 4.08 mm (z score: 8.39, n < 2.5), placing him at high risk for giant coronary artery aneurysm (CAA) formation [Figure 1a and b]. He received intravenous immunoglobulin (IVIG, 2 g/kg) and methylprednisolone (2 mg/kg/day) in addition to high-dose aspirin (80 mg/kg/day). Fever subsided temporarily, but recurred on day 17 of illness (day 7 of admission). Repeat echocardiography revealed worsening CA dilatation (LAD – 6.58 mm, 18.3 z; LCx – 5.83 mm, 14.8 z; RCA – 6.73mm, 15.9 z) [Figure 1c and d, Supplementary Video 1]. A second IVIG infusion was administered, and methylprednisolone was continued. Anticoagulation with warfarin was initiated. Computerized tomography (CT) angiography at three weeks of illness (day 12 of admission) showed giant aneurysms in the LAD (6.92 mm, Z score 19.3), LCx (6.19 mm, Z score 15.5), and RCA (5.08 mm, Z score 14.1), respectively [Figure 2a-c, Supplementary Video 2]. Despite marked dilatation, there was no evidence of intraluminal thrombus. The child recovered well after the second dose of IVIG with resolution of fever and inflammatory parameters and was discharged on aspirin (3 mg/kg/day), warfarin (INR-guided, between 2 and 3), and a tapering dose of steroids, with advice for strict cardiology follow-up.

Close

Figure 1: 2D- Echocardiography findings of the index case with Kawasaki disease at admission (depicted by calipers). (a) LAD (5.11 mm) and LCx (4.47 mm) dimensions. (b) RCA (4.08 mm) dimension. 2D- Echocardiography findings of the index case at day 17 of illness (day 7 of admission, depicted by calipers). (c) LAD (6.58 mm) and LCx (5.83 mm) dimensions. (d) RCA (6.73 mm) dimension. All images are in short parasternal axis view. LAD: Left anterior descending, LCx: Left circumflex, RCA: Right coronary artery.

Export to PPT

Close

Figure 2: Cardiac computed tomography angiography of the index case at 3 weeks of illness (day 12 of admission) depicting (a) left anterior descending, (b) left circumflex, and (c) right coronary artery, dimensions (6.92 mm, 6.19 mm, and 5.08 mm, respectively).

Export to PPT

The serial echocardiographic and CT images in our infant strikingly demonstrate rapid evolution from coronary dilatation to giant aneurysms within a few days, despite administration of two doses of IVIG and steroids. The multifocal distribution of aneurysms in both right and left coronary systems underscores the severity of vascular inflammation in this age group. KD is the leading cause of acquired pediatric heart disease globally. IVIG therapy reduces the risk of CAA from 25% to <5%.^[2] However, infants aged three months or younger represent a special and rare subgroup, accounting for about 1.67% of cases, often presenting either with incomplete clinical features, leading to late diagnosis, or higher rates of treatment resistance needing biologics such as infliximab.^[1,3] Up to 40–60 % of infants in this age group develop coronary complications, compared with 15–20% of older children.^[2,4] Furthermore, giant CAA (≥8 mm or z score ≥10) occurs disproportionately higher in them and is associated with risk of thrombotic occlusion, myocarditis, ischemia, and sudden cardiac death.^[5]

Our case highlights the aggressive and unpredictable vascular course of KD in infants. Despite prompt recognition, early IVIG, adjunctive steroids, and escalation with a second dose of IVIG, the disease progressed to giant CAA. Resistance to IVIG therapy in KD appears to be on the rise, with reported resistance rates of 20–30%, prompting the use of second-line agents such as infliximab, etanercept, and methotrexate.^[1] The absence of thrombus in our patient was fortunate. Still, the lifelong requirement for dual antiplatelet and anticoagulation therapy, along with serial echocardiography and CT imaging, illustrates the burden of these complications.

The presented case emphasizes the unique vulnerability of infants with KD to develop giant CAA. It also reminds clinicians that systemic resolution of fever and normalization of inflammatory markers may not correlate with vascular outcomes, making serial imaging indispensable.