Multisystem Inflammatory Syndrome in Children: A new, mystery diagnosis is defined!

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A Case

A previously healthy 11 year old female presents to the ED with 4 days of fever and abdominal pain. Two days ago she presented to the ED, abdominal CT was performed, and she was discharged home with a diagnosis of mesenteric adenitis. She continues to have abdominal pain with non-bloody diarrhea. Today she began complaining of difficulty breathing, chest pain, and neck pain. Mom reveals that the child had SARS-CoV-2 approximately 2 months prior. In the ED, her vital signs are as follows: T 101, HR 135, RR 30, BP 88/38.

The patient’s history of multiple days of fever plus multisystem involvement (cardiac, respiratory, and GI) prompts screening labs for MIS-C.

Pertinent positives include:

Troponin 0.28ng/mL

BNP 842pg/mL

Fibrinogen 612mg/dL

D-dimer 1616ng/mL

CRP 24.5mg/dL

ESR >145mm/hr

SARS-CoV-2 antibody testing is sent.

What do you know about multisystem inflammatory syndrome in children (MIS-C)?

You may not know much since this is a new syndrome and only seen in pediatric patients. However, MIS-C is definitely a diagnosis to be aware of as it may cross your ER or ICU. Importantly, it can be fatal and earlier treatment seems to lead toward better outcomes!

MIS-C is a novel disease process temporally associated with SARS-CoV-2 exposure or infection.  Pathophysiology is unclear but may be due to viral mimicry of the host resulting in autoantibodies, T-cell recognition of viral antigens expressed on infected cells, formation of immune complexes which activate inflammation, and viral superantigen sequences which activate immune cells (1).

There are a few different published definitions of MIS-C, but the CDC definition is shown in Table 1. MIS-C has features similar to other inflammatory syndromes like Kawasaki disease (Table 2) and Kawasaki shock syndrome, and toxic shock syndrome. Kawasaki disease often affects children younger than 5 years of age, but MIS-C is seen in a much broader age range including teens. Additionally, MIS-C tends to impact the gastrointestinal and neurologic systems more frequently and can lead to myocardial depression and shock if not rapidly treated.

Table 1. CDC case definition for MIS-C
Table 2. Kawasaki disease diagnostic criteria

Radia et al published a systematic review of MIS-C clinical features and presentation encompassing 783 individual cases (2). This study informs much of the data presented here.

Symptoms of MIS-C

The large majority of patients have involvement of at least 4 organ systems, most commonly GI (92%), cardiovascular (80%), hematologic (76%), mucocutaneous (74%), and respiratory (70%) (1). Common symptoms include abdominal pain, diarrhea, vomiting, and rash. Anecdotally, some cases have mimicked appendicitis in presentation. Cough and respiratory distress are infrequent. Over 90% of patients have lab biomarkers indicative of inflammation (elevated ESR, CRP, ferritin, D-dimer, ALT, INR, fibrinogen, neutrophils AND/OR low hemoglobin, lymphocytes, albumin). Elevated troponin levels are common. Coronary aneurysms seen in approximately 10% of patients (1).

Diagnostic Work Up

Many children’s hospitals have created their own algorithms for initiating a work up for MIS-C.

Laboratory evaluation typically includes the following (3):

  • CBC with differential
  • Blood chemistry with liver function tests
  • Cardiac markers
  • UA
  • Blood gas with lactate
  • Inflammatory markers
  • Coagulation panel
  • Blood culture
  • SARS-CoV-2 serologies and swab for RT-PCR

Imaging (3):

  • CXR
  • Abdominal US or CT
  • ECG
  • Echocardiogram

Expected Hospital Course

The majority of patients with MIS-C will need ICU admission. In Radia et al, 77% of patients required fluid resuscitation and/or inotropic support, 28% required respiratory support and 4% required ECMO. Mortality occurred in 1.5% of patients, 2 died from a stroke but cause of death was not stated for a majority of patients.


Goals include decreasing systemic inflammation and restoring organ function.

IVIG (2g/kg) is by-and-large the standard treatment. Glucocorticoids are often utilized as an adjunct. Refractory symptoms have been treated with an IL-6 inhibitor (tocilizumab or siltuximab) or an IL-1Ra inhibitor (anakinra). Aspirin is a standard treatment for Kawasaki disease and is administered in MIS-C particularly if patients meet Kawasaki disease criteria. Lovenox may also be considered depending on the child’s risk factors.

Back to the case

SARS-CoV-2 IgG was positive, and the patient fit diagnostic criteria for MIS-C. The patient was admitted to the ICU and required approximately 8 hours of vasoactive support for refractory hypotension. Echo should mild LV dysfunction but normal coronary arteries, and she will have close follow up with cardiology. She was treated with IVIG and methylprednisolone with symptom resolution and will follow outpatient with infectious disease. Hematology was consulted and recommended prophylactic lovenox which she will remain on at discharge.

The Debrief

  • Think about MIS-C in a patient with prolonged fever, multiorgan system involvement, and a history of or close contact with SARS-CoV-2.
  • If MIS-C is in your differential, send labs to evaluate for inflammation and consider cardiac work up including an echocardiogram.
  • The mainstay of treatment for MIS-C is IVIG +/- steroids and aspirin and/or VTE prophylaxis.
  • MIS-C patients are often treated in consultation with cardiology, hematology, and infectious disease.


  1. Jiang L, Tang K, Levin M, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis. 2020;20(11):e276-e288. doi:10.1016/S1473-3099(20)30651-4
  2. Radia T, Williams N, Agrawal P, et al. Multi-system inflammatory syndrome in children & adolescents (MIS-C): A systematic review of clinical features and presentation [published online ahead of print, 2020 Aug 11]. Paediatr Respir Rev. 2020;S1526-0542(20)30117-2. doi:10.1016/j.prrv.2020.08.001
  3. Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management. Children (Basel). 2020;7(7):69. Published 2020 Jul 1. doi:10.3390/children7070069


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