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Multisystem Inflammatory Syndrome in Children (MIS-C): 2025 Clinical Guidelines and Updates

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Multisystem Inflammatory Syndrome in Children (MIS-C)

 2025 Clinical Guidelines and Updates

Introduction

 Multisystem Inflammatory Syndrome in Children (MIS-C) is a post-infectious complication of SARS-CoV-2 that manifests with systemic inflammation, cardiovascular involvement, and multi-organ dysfunction. As incidence declines post-pandemic, refined diagnostic criteria and evidence-based treatment protocols continue to evolve. This article provides an in-depth review of the 2025 guidelines for diagnosis, management, and follow-up of MIS-C.



 Since its first identification in 2020, MIS-C has posed a diagnostic and therapeutic challenge for pediatricians worldwide. It shares features with Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome. Despite the reduced incidence after widespread vaccination and viral mutation, MIS-C remains a critical condition requiring early recognition and intensive care support.

Epidemiology and Risk Factors

  • Peak age group: 5–13 years
  • Median onset: 2–6 weeks post COVID-19 infection or exposure
  • Male predominance
  • Higher incidence reported in African, Hispanic, and South Asian populations
  • Most children had mild or asymptomatic acute COVID-19

2025 Diagnostic Criteria (Updated AAP/CDC Consensus)

To meet the criteria for MIS-C, all the following must be present:

  1. Age: <21 years
  2. Fever ≥38.0°C for ≥24 hours
  3. Laboratory evidence of inflammation:
    • ↑ CRP, ESR, procalcitonin
    • ↑ Ferritin, D-dimer, IL-6
  4. Multisystem involvement (≥2 systems):
    • Cardiac: myocarditis, arrhythmia, low EF
    • GI: abdominal pain, diarrhea, vomiting
    • Mucocutaneous: rash, conjunctivitis
    • Hematologic: lymphopenia, thrombocytopenia
    • Neurologic: headache, confusion, seizures
  5. Positive SARS-CoV-2 test or known exposure within 4–8 weeks
  6. Exclusion of other plausible diagnoses (e.g., sepsis, Kawasaki)

Key Laboratory Markers

Test Significance
CRP / ESR Non-specific inflammation
Ferritin Hyperinflammation marker
D-dimer / Fibrinogen Thrombotic risk, endothelial dysfunction
Troponin / BNP / NT-proBNP Cardiac involvement
IL-6, IL-1 Cytokine storm indicators
CBC Often shows neutrophilia, lymphopenia

Cardiac Involvement: The Major Concern

  • Echocardiography: Decreased LVEF, pericardial effusion, coronary artery dilatation
  • ECG: Arrhythmias (including AV block, ventricular ectopy)
  • MRI (if available): Myocardial edema and late gadolinium enhancement (LGE)

🩺 Serial echocardiograms are essential during and after the acute phase.

Treatment Guidelines (2025)

Initial Management:

Based on disease severity:

Severity Management
Mild Supportive + low-dose steroids
Moderate IVIG + corticosteroids + aspirin
Severe (shock) ICU admission, high-dose methylprednisolone, IVIG, vasoactive agents

Medications Used

  1. Intravenous Immunoglobulin (IVIG)

    • 2 g/kg over 12 hours
    • Reduces coronary complications

  2. Corticosteroids

    • Mild: Prednisone 1–2 mg/kg/day
    • Severe: Methylprednisolone 10–30 mg/kg/day x 3 days

  3. Aspirin (ASA)

    • 3–5 mg/kg/day for antiplatelet effect
    • Consider stopping after 4–6 weeks if no coronary involvement

  4. Biologics (Refractory cases)

    • Anakinra (IL-1 blockade)
    • Tocilizumab (IL-6 blockade)
    • Infliximab (anti-TNF)

  5. Anticoagulation

    • Consider enoxaparin in patients with LVEF <35% or high D-dimer

2025 Follow-Up Recommendations

Short-Term (2–6 weeks):

  • Repeat echocardiogram
  • Taper steroids over 2–4 weeks
  • Monitor inflammatory markers
  • Cardiology follow-up

Long-Term (3–12 months):

  • Evaluate cardiac function via MRI
  • Neurocognitive assessment
  • Psychological support (high PTSD incidence)

Differential Diagnosis to Rule Out

  • Kawasaki Disease
  • Toxic Shock Syndrome
  • Sepsis
  • HLH/MAS
  • Systemic juvenile idiopathic arthritis (sJIA)

Prognosis and Outcomes (2025 Data)

  • Mortality rate: <2% in developed countries
  • LVEF normalization: Within 2 weeks in 85% of cases
  • Coronary artery involvement: Resolves in majority within 1–3 months
  • Neurologic sequelae: Up to 10% report long-term symptoms (headache, fatigue)

What’s New in 2025?

  • Shift from IVIG-first to steroids-first in moderate cases in some centers
  • Point-of-care troponin and BNP now widely used for triage
  • New MIS-C risk scoring tools under validation (including machine learning–based)
  • MIS-C registries launched in Africa, Asia, and South America for global surveillance

Conclusion

MIS-C remains a high-stakes diagnosis in pediatrics, requiring multidisciplinary management. Early recognition, tailored immunomodulatory therapy, and long-term cardiac follow-up are key to minimizing complications. As our understanding of post-COVID immune responses deepens, MIS-C will continue to evolve both diagnostically and therapeutically.

Related Article you Might like to Read:

2. “COVID, Immunity, and Long-Term Organ Damage: Unmasking the Lingering Threat”

References

  1. Henderson LA, et al. (2025). ACR/MIS-C Consensus Update. Pediatrics Rheumatology Journal.
  2. Feldstein LR, et al. (2023). Long-Term Outcomes of MIS-C. JAMA.
  3. CDC Clinical Guidance for MIS-C (2025 Update).
  4. Abrams JY, et al. (2024). Predictors of Cardiac Dysfunction in MIS-C. Circulation.
  5. World Health Organization (2024). Global Surveillance of MIS-C.
  6. McArdle AJ, et al. (2022). Treatment of Pediatric Inflammatory Syndromes. Lancet Child & Adolescent Health.


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