Cardiovascular Medicine Book

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Multisystem Inflammatory Syndrome

Aka: Multisystem Inflammatory Syndrome, MIS-C
  1. See Also
    1. Covid19
    2. Kawasaki Disease
  2. Epidemiology
    1. First identified during Spring 2020 with onset of Covid19 pandemic
    2. Age
      1. Initially identified in children and unlike Kawasaki (age <11 years) extended to age 21
      2. Has since been reported in adults
        1. Morris (2020) MMWR Morb Mortal Wkly Rep 69:1450-56 [PubMed]
        2. https://www.cdc.gov/mmwr/volumes/69/wr/mm6940e1.htm
  3. Pathophysiology
    1. Systemic inflammatory condition as a complication of COVID-19, and similar to Kawasaki Disease
  4. Indications: Evaluation for MIS-C
    1. Suspected or confirmed COVID-19 within prior 4 weeks AND
    2. Fever >3 days AND
    3. No other apparent explanation AND
    4. Two or more of the following systems involved (or unexplained Fever >5 days)
      1. Neurologic findings
        1. Headache or irritability
        2. Neurologic deficits
      2. Conjunctivitis
      3. Oral Lesions or other oral changes
      4. Lymphadenopathy
      5. Swelling of hands or feet
      6. Gastrointestinal findings
        1. Abdominal Pain or Diarrhea
        2. Nausea or Vomiting
      7. Urethritis
      8. Arthralgias or Arthritis
      9. Dermatologic findings
        1. Polymorphic rash
        2. Scaling or peeling of skin (Exfoliative Dermatitis)
  5. Labs
    1. First-Line - Tier 1 Screening
      1. Complete Blood Count with platelets and differential
      2. Comprehensive metabolic panel (Electrolytes, Renal Function tests, Liver Function Tests, albumin)
      3. Erythrocyte Sedimentation Rate
      4. C-Reactive Protein
      5. Covid19 Test (typically nasopharyngeal PCR)
    2. First-Line - Tier 2 Screening
      1. Indications for Tier 2 tests (from Tier 1 Screening)
        1. C-Reactive Protein or CRP >5 mg/L or Erythrocyte Sedimentation Rate or ESR >40 mm/h AND
        2. At least one of the following
          1. Absolute Lymphocyte Count <1000/ul
          2. Platelet Count <150,000/ul
          3. Serum Sodium <135 mmol/L
          4. Neutrophilia
          5. Hypoalbuminemia (e.g. Serum Albumin <3 g/dl)
      2. Tier 2 Tests
        1. INR and PTT
        2. D-Dimer
        3. Serum Troponin
        4. NT-BNP
        5. Urinalysis (and consider Urine Culture)
        6. Blood Culture
    3. Additional Testing to consider based on Consultation
      1. Fibrinogen
      2. Factor VIII and Von-Willebrand profile
      3. Antithrombin III
      4. Procalcitonin
      5. Serum Ferritin
      6. Serum Triglycerides
      7. Total IgG
      8. Mycoplasma PCR
      9. Tick-Borne Illness Serology (e.g. Lyme Disease, Babesiosis, Anaplasmosis, Rickettsia - depending on region)
      10. Antiphospholipid Antibody profile and Lupus Anticoagulant Profile
      11. Cytokine Panel (e.g. IL1, IL6, IL8, TNFa)
      12. Lactate Dehydrogenase
      13. Uric Acid
      14. Peripheral Smear
  6. Diagnostics
    1. First-Line
      1. Electrocardiogram
  7. Imaging
    1. First-Line
      1. Chest XRay
    2. Second-Line (suspected MIS-C)
      1. Echocardiogram
  8. Differential Diagnosis
    1. Multisystem Infammatory Syndromes
      1. Covid19
      2. Kawasaki Disease
    2. Other Infections
      1. Toxic Shock Syndrome
      2. Septic Shock
      3. Mycoplasma pneumonia
      4. Viral Infections (e.g. Adenovirus, other Enteroviruses)
      5. Measles
      6. Tick-Borne Illness
      7. Leptospirosis
      8. Rheumatic Fever
    3. Rheumatologic Conditions
      1. Vasculitis
      2. Systemic Lupus Erythematosus (SLE)
      3. Juvenile Idiopathic Arthritis
      4. Macrophage Activation Syndrome
      5. Hemophagocytic lymphohistiocytosis
    4. Adverse Drug Reaction
      1. See Serious Cutaneous Adverse Reaction
      2. Stevens-Johnson Syndrome
      3. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS Syndrome)
    5. Miscellaneous
      1. Malignancy
  9. Management: Indications for Inpatient Evaluation and Management
    1. Cardiac involvement
    2. Hypoxia
    3. Dehydration
    4. Lymphocytes <1000/ul
    5. Platelets <150k or >450k
    6. C-Reactive Protein or CRP >30 mg/L
    7. Erythrocyte Sedimentation Rate or ESR >40 mm/h
    8. Serum Albumin <3 g/dl
    9. Significant Anemia for age
    10. Coagulopathy
  10. Management: General
    1. See Covid19 for respiratory management
    2. Multispecialty Consultation (Infectious disease, hematology and oncology, cardiology, rheumatology)
    3. Immunomodulatory agents, antiplatelet agents and Anticoagulation per Consultation
    4. Consider empiric antibiotics
      1. Ceftriaxone (or if immunocompromised, Cefepime) AND
      2. Consider Vancomycin (if Septic Shock, Meningitis, Central Line) AND
      3. Consider Metronidazole (if suspected abdominal source of infection) AND
      4. Consider Doxycycline (if suspected Tick Borne Illness)
  11. Resources
    1. Children's Hospital of Philadelphia MIS-C Evaluation Protocol
      1. https://www.chop.edu/clinical-pathway/multisystem-inflammatory-syndrome-mis-c-clinical-pathway
    2. American College of Rheumatology
      1. https://www.rheumatology.org/Portals/0/Files/ACR-COVID-19-Clinical-Guidance-Summary-MIS-C-Hyperinflammation.pdf
  12. References
    1. (2020) University of Minnesota Masonic Guidance on Emergency Management MIS-C in Children
    2. Jiang (2020) Lancet Infect Dis [PubMed]
      1. https://www.thelancet.com/action/showPdf?pii=S1473-3099%2820%2930651-4

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