P3C310: Small Kid, Giant Aneurysms: The Use of Anakinra in Ivig-resistant Kawasaki Disease

Introduction: Kawasaki Disease (KD) is a medium vessel vasculitis of childhood that causes inflammation to the coronary arteries and results in coronary artery aneurysms (CAA) in up to 25% of untreated cases. KD standard of care includes intravenous immunoglobulin (IVIG) and high-dose aspirin (ASA) within the first 10 days of fever. Resistance to IVIG in KD patients is defined by recurrence of fever 36 hours after completion of IVIG. This is associated with an increased risk of CAA, which can have devastating implications, such as thrombosis, myocardial ischemia, cardiac dysfunction, or death. Data on the treatment of IVIG-resistant KD is limited and without clear guidelines. Anakinra, an interleukin-1 (IL-1) receptor antagonist, is used as an anti-inflammatory agent for several rheumatologic diseases, with implications for KD.

Case Description: An ex-full term, non-Japanese, 4-month-old male presented with fever for 15 days, conjunctival injection, erythematous mucous membranes, and maculopapular rash in the lower extremities with edematous hands/feet. Labs showed neutrophilic leukocytosis, anemia, thrombocytosis, elevated inflammatory markers, and hypoalbuminemia. He was diagnosed with classic KD and treated with standard therapy. Echocardiogram on presentation noted giant saccular aneurysm of the left anterior descending artery (LAD) with z-score of >15 and medium right coronary artery (RCA) aneurysm with z-score of 8.5 (Figure 1). Given these features, a two-week prednisolone course was added as adjuvant therapy and low molecular weight heparin was used for thromboprophylaxis. Inflammatory markers and echocardiograms were monitored for treatment response.
5 days after completing prednisolone, the patient presented with irritability and up-trending inflammatory markers; CAAs were stable and he was afebrile. He was readmitted for initiation of a 4-week course of anakinra (4mg/kg/day subcutaneous) for persistent systemic inflammation. 2 weeks after starting anakinra, the patient remained well with normal inflammatory markers.

Discussion: Given our patient’s age and delayed diagnosis, he was at high-risk for IVIG-resistant KD. Optimal management was complicated by giant CAAs and his non-Japanese background. Applying our patient to a new predictive model for non-Japanese KD patients, prednisolone was added given moderate-quality evidence suggesting that this adjuvant therapy, in combination with IVIG reduces the progression of CAAs compared to IVIG alone in KD patients with CAAs. Although our patient remained afebrile following IVIG, additional immunomodulation was necessary given persistent systemic inflammation in the subacute period in a child with high-risk features for CAA complications. Although the literature is limited on anakinra’s use in KD, a recent Phase II study found anakinra safe in IVIG-resistant KD and some efficacy in reductions of systemic inflammation and coronary abnormalities. Further research on anakinra’s use in IVIG-resistant KD patients is needed.

Conclusion: This case highlights the importance of timely diagnosis of KD and the potential benefits of IL-1 receptor antagonists in reducing systemic inflammation in IVIG-resistant KD patients.