Immunology · Year 2 · from Immunology
Case 3: Multisystem Inflammatory Syndrome in Children (MIS-C)
Clinical Image
Source: Wikipedia - Multisystem inflammatory syndrome in children - CC BY-SA 4.0
Case Presentation
A 7-year-old previously healthy male presents with 5 days of persistent high fever (40.2C), diffuse abdominal pain with vomiting and diarrhea, a polymorphous erythematous rash on the trunk and extremities, bilateral non-exudative conjunctival injection, and cracked erythematous lips. His parents report he had a mild upper respiratory infection 4 weeks ago that resolved without treatment; no COVID-19 testing was performed at that time. On examination, he appears toxic with HR 142 bpm, BP 78/48 mmHg (hypotensive for age), RR 30/min, and SpO2 95% on room air. There is diffuse abdominal tenderness without peritoneal signs, bilateral cervical lymphadenopathy (>1.5 cm), and palmar erythema with early desquamation of the fingertips. Laboratory studies reveal CRP 285 mg/L, ESR 82 mm/hr, ferritin 1,450 ng/mL, D-dimer 6.8 mcg/mL FEU, fibrinogen 680 mg/dL, procalcitonin 12.4 ng/mL, troponin I 0.34 ng/mL, BNP 2,400 pg/mL, albumin 2.1 g/dL, sodium 128 mEq/L, and lymphopenia (ALC 0.6 x 10^9/L). SARS-CoV-2 nucleocapsid antibody is positive, confirming prior infection. Echocardiography reveals mildly dilated left anterior descending coronary artery (Z-score +2.8) with reduced ejection fraction of 38%. He is admitted to the pediatric ICU, started on IV immunoglobulin 2 g/kg over 12 hours, methylprednisolone 2 mg/kg/day, aspirin 3-5 mg/kg/day for coronary involvement, and norepinephrine for fluid-refractory shock.
Key Learning Points
- MIS-C is a post-infectious hyperinflammatory syndrome occurring 2-6 weeks after SARS-CoV-2 infection, driven by a superantigen-like motif on the SARS-CoV-2 spike protein that cross-links TCR V-beta regions with MHC class II, causing polyclonal T cell activation and massive cytokine release
- The clinical overlap with Kawasaki disease (conjunctivitis, mucosal changes, rash, coronary artery involvement) reflects shared downstream pathways of immune-mediated vasculitis, but MIS-C is distinguished by older age at presentation, more prominent cardiac dysfunction/shock, and gastrointestinal involvement
- Coronary artery aneurysms in MIS-C are monitored by serial echocardiography using Z-scores; aneurysms with Z-score >2.5 warrant antiplatelet therapy, while giant aneurysms (Z-score >10) require anticoagulation
- IVIG works by Fc receptor blockade, anti-idiotypic antibody effects, and modulation of complement activation, while corticosteroids suppress NF-kB-mediated transcription of proinflammatory cytokines