Case Presentation: A previously healthy 7-week-old female presented to the infectious disease service with a 7-day history of fever, papular rash of the face and body, edema of the hands and feet, and cracking of the lips. A diagnosis of incomplete Kawasaki Disease (KD) was confirmed by demonstration of aneurysmal dilation of the right coronary artery (RCA), left main coronary artery (LMCA), and left anterior descending coronary artery (LAD) on echocardiogram. Hyperferritinemia and developing cytopenias raised suspicion for macrophage activation syndrome (MAS) complicating KD. The patient was treated with IVIG, methylprednisolone, aspirin, and anakinra. At discharge, ectasias of the LAD, RCA, and LMCA were stable, and MAS criteria were no longer met. Two days after discharge, the LAD progressed to a giant fusiform aneurysm (z score= +14). The patient was readmitted, and anakinra was increased from 8 mg/kg daily to 10 mg/kg daily. Increasing doses of anakinra in conjunction with first line treatment modalities resulted in disease remission as noted by resolution of fever, coronary aneurysms, and clinical features of KD, and normalization of blood counts and inflammatory markers.
Discussion: KD is a leading cause of acquired heart disease in children and is rarely complicated by MAS. Though KD rarely presents in children less than 6 months of age it is associated with increased morbidity and mortality in this population. MAS requires prompt recognition and treatment as mortality rates may be up to 53%.(1) A well-defined treatment protocol exists for KD, but best practices for MAS complicating rheumatologic disease are less clear. Recent literature has implicated targeted therapy including TNF-alpha and IL-1 blockade as a method of treatment intensification in high risk cases of KD.(2,3) It has been found that individuals who develop coronary changes have higher levels of circulating IL-1 compared to those without coronary pathology.(4) Anakinra, an IL-1 receptor antagonist has been used as a second or third-line treatment option for KD patients who have ongoing systemic inflammation secondary to failed IVIG therapy.(5,6) Additionally, anakinra has been recommended in the treatment of MAS complicating rheumatologic disease.(7) Our patient represents the unlikely occurrence of KD in a young infant as well as the development of MAS complicating KD and demonstrates the clinical course of coronary pathology and MAS in response to the early administration of high dose anakinra in conjunction with first line treatment modalities and prior to IVIG failure. Our patient’s impressive resolution of coronary changes and MAS symptoms, in addition to mounting evidence showing the role of IL-1 in KD, support ongoing research about the role of blocking IL-1 to directly target pathologic mechanisms involved in KD.
Conclusions: Our case highlights severe KD complicated by MAS, and a positive response to anakinra in a 7-week-old infant. Further studies are indicated to understand the role of anakinra in the prevention and treatment of KD, especially those with a disease process complicated by MAS or significant coronary changes.