What is the next step in managing a patient with suspected Multisystem Inflammatory Syndrome in Children (MIS-C) who is now afebrile?

Management of Afebrile MIS-C Patient

Even after defervescence, a patient with suspected or confirmed MIS-C requires continued hospitalization with serial cardiac monitoring, trending of inflammatory markers and cardiac biomarkers, and completion of the full diagnostic and treatment protocol—resolution of fever does not indicate resolution of disease or safety for discharge. 1

Critical Monitoring Requirements Post-Defervescence

Cardiac Surveillance

• Continue EKG monitoring every 48 hours minimum while hospitalized, as electrical conduction abnormalities can develop after initial presentation and even after fever resolves 1
• Maintain continuous telemetry if any conduction abnormalities are present 1
• Trend cardiac biomarkers (BNP/NT-proBNP and troponin T) until normalization, as elevated levels indicate ongoing cardiac involvement regardless of fever status 1, 2
• Schedule follow-up echocardiograms at 7-14 days and 4-6 weeks after initial presentation, with more frequent imaging if LV dysfunction or coronary artery abnormalities were detected 1, 2

Laboratory Monitoring

• Serial inflammatory markers (CRP, ESR, ferritin) should be trended to assess treatment response and disease activity, as these may remain elevated despite defervescence 1, 3
• Complete blood counts to monitor for thrombocytosis (platelets ≥450,000/μl), which requires aspirin therapy 1
• D-dimer levels correlate with disease severity and thrombotic risk 3, 4

Treatment Continuation Despite Afebrile Status

Immunomodulatory Therapy

• Complete the full course of initiated immunomodulatory treatment (IVIG 2 gm/kg and/or methylprednisolone 1-2 mg/kg/day) even if fever has resolved, as MIS-C represents a continuum of hyperinflammation requiring adequate immunosuppression 2, 1
• Do not discontinue therapy based solely on defervescence, as cardiac complications and coronary artery aneurysms can progress despite fever resolution 1

Antiplatelet/Anticoagulation Management

• Initiate low-dose aspirin (3-5 mg/kg/day; maximum 81 mg/day) if the patient has Kawasaki disease-like features and/or thrombocytosis, continuing until platelet count normalizes and normal coronary arteries are confirmed at ≥4 weeks 1, 2
• Therapeutic anticoagulation with enoxaparin is required for documented thrombosis or ejection fraction <35%, continuing at least 2 weeks after discharge 1, 2
• Avoid aspirin if platelet count is ≤80,000/μl 1

Common Pitfalls to Avoid

Premature Discharge

• Never discharge based on fever resolution alone, as MIS-C patients can develop progressive cardiac involvement rapidly even after becoming afebrile 1
• Well-appearing afebrile children still require completion of tier 2 diagnostic testing if not already performed, including echocardiogram, EKG, and cardiac biomarkers 1

Inadequate Follow-Up Planning

• Ensure close cardiology follow-up is arranged before discharge, as cardiac complications may not fully resolve at discharge (20% of myocarditis cases, 26.3% of coronary aneurysm cases in one cohort) 3
• Cardiac MRI at 2-6 months should be considered for patients who had moderate-to-severe LV dysfunction (ejection fraction <50%), as myocardial fibrosis and scarring are potential long-term complications 1

Monitoring for Late Complications

• Long-term follow-up is essential for neuropsychiatric findings (6.2% in follow-up), persistent gastrointestinal symptoms (14.2%), cardiac findings (14.2%), and pulmonary symptoms (8%), which occur even after initial recovery 4
• Recurrent hospitalization was required in 6.2% of patients during follow-up 4

Disposition Decision Algorithm

For hospitalized patients now afebrile:

• Continue inpatient monitoring until inflammatory markers trend downward, cardiac biomarkers normalize or stabilize, and at least 24-48 hours of clinical stability is achieved 1
• Complete the full immunomodulatory treatment course as planned 2
• Obtain repeat echocardiogram before discharge if initial study showed abnormalities 1
• Arrange cardiology follow-up within 7-14 days of discharge 1

For outpatients under investigation who become afebrile:

• If initial evaluation showed reassuring vital signs, physical examination, and tier 1 laboratory results, close clinical follow-up can be ensured without hospitalization 1
• However, any patient with elevated inflammatory markers, cardiac involvement, or concerning physical findings requires hospital admission for tier 2 testing and monitoring, regardless of current fever status 1