MIS-C Criteria
➔ Multisystem Inflammatory Syndrome in Children (MIS-C)
➔ 2 guidelines, WHO and CDC
◆ Differs in age and duration of fever
WHO
Children and adolescents 0–19 years of age with
fever > 3 days
AND two of the following:
Rash or bilateral non-purulent conjunctivitis or
muco-cutaneous inflammation signs (oral, hands or
feet).
Hypotension or shock.
Features of myocardial dysfunction, pericarditis,
valvulitis, or coronary abnormalities (including ECHO
findings or elevated Troponin/NT-proBNP),
Evidence of coagulopathy (by PT, PTT, elevated
d-Dimers).
Acute gastrointestinal problems (diarrhoea, vomiting,
or abdominal pain).
AND
Elevated markers of inflammation such as ESR,
C-reactive protein, or procalcitonin.
AND
No other obvious microbial cause of inflammation,
including bacterial sepsis, staphylococcal or
streptococcal shock syndromes.
AND
Evidence of COVID-19 (RT-PCR, antigen test or
serology positive), or likely contact with patients with
COVID-19.
CDC
An individual aged <21 years presenting with fever*,
laboratory evidence of inflammation**, and evidence
of clinically severe illness requiring hospitalization,
with multisystem (>2) organ involvement (cardiac,
renal, respiratory, hematologic, gastrointestinal,
dermatologic or neurological);
AND
No alternative plausible diagnoses;
AND
Positive for current or recent SARS-CoV-2 infection
by RT-PCR, serology, or antigen test; or exposure to
a suspected or confirmed COVID-19 case within the
4 weeks prior to the onset of symptoms.
*Fever >38.0°C for ≥24 hours, or report of subjective
fever lasting ≥24 hours
**Including, but not limited to, one or more of the
following: an elevated C-reactive protein (CRP),
erythrocyte sedimentation rate (ESR), fibrinogen,
procalcitonin, d-dimer, ferritin, lactic acid
dehydrogenase (LDH), or interleukin 6 (IL-6),
elevated neutrophils, reduced lymphocytes and low
albumin
Additional comments:
Some individuals may fulfill full or partial criteria for
Kawasaki disease but should be reported if they
meet the case definition for MIS-C.
Consider MIS-C in any pediatric death with evidence
of SARS-CoV-2 infection.
Patients with MIS-C usually present with persistent fever,
abdominal pain, vomiting, diarrhea, skin rash,
mucocutaneous lesions and, in severe cases, with
hypotension and shock. They have elevated laboratory
markers of inflammation (e.g., CRP, ferritin), and in a
majority of patients laboratory markers of damage to the
heart (e.g., troponin; B-type natriuretic peptide (BNP) or
proBNP). Some patients develop myocarditis, cardiac
dysfunction, and acute kidney injury. Not all children will
have the same signs and symptoms, and some children
may have symptoms not listed here. MIS-C may begin
weeks after a child is infected with SARS-CoV-2. The child
may have been infected from an asymptomatic contact
and, in some cases, the child and their caregivers may not
even know they had been infected.
Laboratory Testing
● Testing aimed at identifying laboratory
evidence of inflammation as listed in the
Case Definition section is warranted.
● Similarly, SARS-CoV-2 detection by RT-PCR
or antigen test is indicated.
● Where feasible, SARS-CoV-2 serologic
testing is suggested, even in the presence of
positive results from RT-PCR or antigen
testing. Any serologic testing should be
performed prior to administering intravenous
immunoglobulin (IVIG) or any other
exogenous antibody treatments.
Other Evaluations
Given the frequent association of MIS-C with cardiac
involvement, many centers are performing cardiac
testing including, but not limited to:
●
●
●
echocardiogram;
electrocardiogram;
cardiac enzyme or troponin testing (per the
center’s testing standards); and
● B-type natriuretic peptide (BNP) or
NT-proBNP.
Other testing to evaluate multisystem involvement
should be directed by patient signs or symptoms.
Additionally, testing to evaluate for other potential
diagnoses should be directed by patient signs or
symptoms.
American College of Rheumatology MIS-C Treatment Guidelines
Common clinical features
➔ Fever
➔ mucocutaneous findings (rash, conjunctivitis, edema of the hands/feet, red/cracked lips, and strawberry
tongue)
➔ myocardial dysfunction
➔ cardiac conduction abnormalities
➔ Shock
➔ gastrointestinal symptoms
➔ Lymphadenopathy
➔ Neurologic involvement (severe headache, altered mental status, cranial nerve palsies, or
meningismus, in select patients)
➔ Nonspecific
Cardiac involvement
Left ventricular (LV) dysfunction (20-55%), coronary artery dilation or coronary artery aneurysm (CAA) 20%,
and electrical conduction abnormalities. Valvular dysfunction and pericardial effusion (less frequently)
Full diagnostic evaluation:
ECG and echocardiogram (to include quantification of LV size and systolic function using end-diastolic volume
(and z-score) and ejection fraction (EF) )
Systemic inflammation:
In addition to the ESR and CRP level, MIS-C patients typically demonstrate other markers of inflammation,
including high d-dimer levels, moderately elevated ferritin levels (often ranging from 500 to 2,000 ng/dl),
profoundly increased procalcitonin levels in the absence of bacterial infection, and increased lactate
dehydrogenase (LDH) levels.
MIS-C
Kawasaki Disease
African descent and possibly those of Hispanic
descent
Japan
found in children ranging from age 3 months to age
17 years
diagnosed before age 5 years
Commonly present with LV dysfunction and shock
<10% present with KD shock syndrome
gastrointestinal and neurologic symptoms more
frequently encountered
Reported to occur but less likely
Lower platelet count, lower absolute lymphocyte
count, and higher CRP levels
Cardiac management of MIS-C
Repeat echocardiograms be obtained from all children with MIS-C at a minimum of 7–14 days and then
4–6 weeks after the initial presentation
For those patients with cardiac involvement noted during the acute phase of illness, another
echocardiogram at 1 year after MIS-C diagnosis could be considered. Children with LV dysfunction and
CAAs will require more frequent echocardiograms.
Long-term complications of myocardial inflammation not known. Cardiac magnetic resonance imaging
at 2–6 months post–acute illness in those patients who had moderate-to-severe LV dysfunction will
allow for evaluation of fibrosis and scarring.
For patients with electrical conduction abnormalities. EKG should be performed at a min- imum of every
48 hours in patients who are hospitalized and at each follow-up visit.
Treatment
A stepwise approach to immunomodulatory treatment in MIS-C is recommended, with intravenous
immunoglobulin (IVIG) and/or glucocorticoids considered as first-tier agents.
Both IVIG and glucocorticoids, either alone or in combination, are the most commonly used
immunomodulatory medications reported to date in MIS-C patients
IVIG at a dose of 2 gm/kg
low-to-moderate doses (1–2 mg/kg/day) of glucocorticoids were sufficient to treat many MIS-C patients
Anakinra is a recommended treatment for MIS-C patients who are refractory to IVIG and/or
glucocorticoids.
22% of MIS-C patients recovered with supportive care. some patients with mild symptoms may require
only close monitoring, without the use of IVIG and/or glucocorticoids
Antiplatelet and anticoagulation therapy in MIS-C
➢ Patients with MIS-C describe marked abnormalities in the coagulation cascade, including prominent
elevations in d-dimer and fibrinogen levels, a variable effect on the platelet count, and a high clot
strength as determined by thromboelastography
➢ With increased risk of thrombosis
➢ Antiplatelet agents such as aspirin are recommended in patients with KD, because of the presence of
platelet activation, thrombocytosis, altered flow dynamics in the affected coronary arteries, and
endothelial damage characteristic of this disease .
○ Accordingly, low-dose aspirin (3–5 mg/kg/day up to 81 mg once daily) is recommended in all
MIS-C patients with KD features, CAAs, and thrombocytosis.
○ Anti-acid treatments should be used to prevent gastrointestinal complications in MIS-C patients
who are taking steroids and aspirin