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.

Study Overview

• Status: Not yet recruiting
• Conditions: Kawasaki Disease; Macrophage Activation Syndrome (MAS)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Teresa Giani, MD; Phone Number: +390555662924; Email: teresa.giani@meyer.it

Study Locations

• Italy
  • Italy
    • Florence, Italy, Italy, 50139
      • Azienda Ospedaliero-Universitaria IRCCS Meyer
      • Contact: Teresa Giani, MD; Phone Number: +390555662924; Email: teresa.giani@meyer.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Since no validated or universally accepted diagnostic criteria currently exist for MAS occurring in the context of KD, the diagnosis of MAS will be based on the clinical judgment of the treating physician.

To minimize the risk of misdiagnosis, all cases will be independently and critically reviewed by three experienced pediatric rheumatologists.

Control groups will consist of age- and sex-matched patients, divided as follows:

• Patients with KD resistant to first-line therapy
• Patients with KD responsive to first-line therapy For each patient with KD complicated by MAS included in the study, 2 KD-responsive and 2 KD-resistant patients will be enrolled.

The goal is to include at least 30 MAS-KD patients, along with 60 KD-resistant controls and 60 KD-responsive controls.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
MAS-KD patients.; Patients with diagnosis of KD made according to the 2024 AHA guidelines.
KD-resistant controls; Patients with KD resistant to first-line therapy
KD-responsive controls; Patients with KD responsive to first-line therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MAS-KD population	Definition of the proportion of patients with KD who develop MAS in the study population.	From the study initiation date onward for 36 months
Clinical and laboratory features of MAS KD patients	Adjusted Odds ratios of clinical and laboratory risk factors	From the study initiation date onward for 36 months
Applicability and diagnostic performance of currently available MAS classification criteria	Evaluation of diagnostic performance metrics (sensitivity, specificity, positive predictive value, negative predictive value) of existing MAS criteria when applied to KD patients.	From the study initiation date onward for 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Applicability and diagnostic performance of currently available MAS classification criteria	Evaluation of diagnostic performance metrics (sensitivity, specificity, positive predictive value, negative predictive value) of existing MAS criteria when applied to KD patients.	From the study initiation date onward for 36 months
Heterogeneity of MAS KD population	Differences in clinical course based on e.g., intensive care unit admission (present/absent, days), duration of fever (days), coronary involvement (present/absent,) among three groups of Patients: patients with KD complicated by MAS; patients with KD resistant to first-line therapy; patients with KD responsive to first-line therapy.	From the study initiation date onward for 36 months
MAS diagnosis	Time from KD onset to MAS diagnosis and its correlation with clinical outcomes;	From the study initiation date onward for 36 months
Treatment and clinical response of MAS KD patients	Description of treatments used for MAS (e.g., corticosteroids, IVIG, biologics) and the corresponding clinical response.	From the study initiation date onward for 36 months
Heterogeneity of MAS KD population	Differences in treatment strategies based on e.g., intensive care unit admission (present/absent, days), duration of fever (days), coronary involvement (present/absent,) among three groups of Patients: patients with KD complicated by MAS; patients with KD resistant to first-line therapy; patients with KD responsive to first-line therapy.	From the study initiation date onward for 36 months
Heterogeneity of MAS KD population	Differences in outcomes based on e.g., intensive care unit admission (present/absent, days), duration of fever (days), coronary involvement (present/absent,) among three groups of Patients: patients with KD complicated by MAS; patients with KD resistant to first-line therapy; patients with KD responsive to first-line therapy.	From the study initiation date onward for 36 months

Collaborators and Investigators

• Sponsor: Meyer Children's Hospital IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: January 20, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Immune System Diseases; Skin Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Skin Diseases, Vascular; Vasculitis; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Mucocutaneous Lymph Node Syndrome; Macrophage Activation Syndrome
• Other Study ID Numbers: MASKd

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No