Emergency Department, ICU and Inpatient Clinical Pathway for
Evaluation of Possible Multisystem Inflammatory Syndrome (MIS-C)

Clinical/Historical Features to Guide Need for Evaluation:
  • Rash (more common)
    • Polymorphic, maculopapular, petechial, NOT vesicular
  • GI Symptoms (more common)
    • Diarrhea, abdominal pain, vomiting
  • Extremity changes
    • Erythema and edema of the hands and feet in acute phase
  • Oral Mucosal Changes
    • Erythema and cracking of lips, strawberry tongue, and/or erythema of oral and pharyngeal mucosa
  • Conjunctivitis (more common)
    • May be bulbar or limbic-involving, without exudate
  • Lymphadenopathy (less common)
    • Cervical > 1.5 cm, unilateral (infrequently observed)
  • Neurologic Symptoms
    • Headache, irritability, lethargy, altered mental status, neck stiffness, cranial nerve palsies
  • Epidemiologic Link to COVID
    • Patient with history of COVID disease or close contact with known Positive COVID case in past 4-6 weeks, or person placed in quarantine
Evaluation for Possible MIS-C in a stable patient
Suspected MIS-C with Shock
Fever/history of fever ≥ 38.0°C for ≥ 3 days
≥ 2 Clinical /Historical Features OR strong clinical suspicion with shorter fever duration

Review Kawasaki Pathway
Fever/history of fever ≥ 38.0°C for ≥ 1 day
Evidence of myocardial dysfunction or
Hypotension/vasopressor requirement
≥ 2 Clinical/Historical Features
Initial Laboratory Testing
  • Other testing as clinically indicated to identify cause of fever, based on clinical features
  • Sepsis Pathway — Use ED Sepsis Order Set
  • Additional Diagnostic Laboratory Studies
    • Add COVID PCR, RRP, Troponin, BNP, D-dimer, Ferritin, Save Our Specimen, ECG
  • Fluid Resuscitation, Vasopressors
  • Antibiotics
  • Echo as clinically indicated
Labs and Physical
Exam Reassuring
Labs or exam concerning but inconsistent with MIS-C
  • CRP ≥ 3 mg/dL   and/or
  • ESR ≥ 40 mm/hr
  • AND
  • Lymphopenia < 1k   or
  • Thrombocytopenia < 150k   or
  • Na < 135   or
  • Abnormal creatinine for age
Admit to Inpatient
Consider Further Evaluation
  • Additional ancillary labs:
    • Troponin, BNP, EKG
    • Save our specimen
  • Cardiology Consultation if:
    • For review of abnormal ECG
    • Abnormal BNP, troponin
    • Concerns on PE
  • Consider culture, antibiotics
    Patients likely to have MIS-C can deteriorate rapidly despite fluid resuscitation, consider PICU admit for pts requiring >40-60 mL/kg to achieve VS stability
  • Tolerates PO
  • Reassuring PE
  • PCP follow-up 24-48 hrs

Guidance is based on expert consensus. As this guidance will evolve, consider ID, Rheumatology, Dysregulated Immune Response Team and Critical Care Medicine consultation for individualized recommendations for suspected cases.

Posted: May 2020
Revised: July 2021
Authors: K. Chiotos, MD; D. Corwin, MD; L. Sartori, MD; M. Congdon, MD; J. Lavelle, MD; S. Swami, MD; J. Burnham, MD; H. Bassiri, MD; A. John, MD; F. Balamuth, MD; K. Cohn, MD; M. Blackstone, MD; J. Callahan, MD; V. Kampalath, MD; R. Rempell, MD; M. Elias, MD; T. Giglia, MD; C. Witmer, MD; D. Davis, MD; C. Kerman, MD; D. Whitney, MD; E. Behrens, MD; D. Teachey, MD; C. Jacobstein, MD