MASKd: a Study on Kawasaki Disease (KD) Complicated by Macrophage Activation Syndrome (MAS)

MACROPHAGE ACTIVATION SYNDROME IN KAWASAKI DISEASE: Features, Treatment, Outcome, Predictive and Diagnostic Factors (The MASKd Study)

Kawasaki Disease (KD) is one of the most common vasculitides in childhood and represents a leading cause of acquired heart disease in developed countries. Macrophage Activation Syndrome (MAS) is a potentially life threatening hyperinflammatory condition belonging to the spectrum of hemophagocytic lymphohistiocytosis (HLH), and it can complicate various rheumatologic diseases. Awareness of MAS in the context of KD has recently increased, supporting the hypothesis that it is an underdiagnosed complication. The study aims to define the epidemiology, clinical characteristics, management, and therapeutic strategies of MAS in patients with KD, through a multicenter data collection in Europe.

KD most frequently affects young children under the age of 5. Its epidemiology varies by geographical location and season. The course of KD can be complicated by the development of MAS.

Clinical similarities between KD-especially refractory KD-and MAS, combined with the lack of specific diagnostic criteria, may hinder accurate and timely identification of MAS in KD, complicating treatment decisions and worsening clinical outcomes. Given that MAS is associated with a significant risk of multi-organ failure (MOF), patient prognosis may be severely compromised, with increased morbidity and mortality. Therefore, early recognition of MAS is crucial in order to implement targeted therapeutic strategies as promptly as possible.

In this retrospective-prospective, observational, descriptive, international multicenter study, we aim to:

• Analyze the clinical features, management, and outcomes of patients with KD complicated by MAS to describe this complication and identify potential risk factors for MAS development;
• Evaluate the performance of currently available MAS diagnostic criteria in KD patients and identify specific diagnostic criteria for this condition.

The study will include international pediatric rheumatology centers affiliated with the PReS network.

Inclusion Criteria:

• Age between 4 weeks and under 18 years at the time of KD diagnosis
• Diagnosis of KD made according to the 2024 AHA guidelines
• Diagnosis of MAS made by the attending physician within 30 days from the onset of KD.

Exclusion Criteria:

• Unconfirmed diagnosis of KD (e.g., mimicking conditions)
• Primary (genetic) HLH
• Lack of informed consent
• MAS diagnosed more than 30 days after or more than 15 days before the onset of KD