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Multisystem Inflammatory Syndrome
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Multisystem Inflammatory Syndrome
, Multisystem Inflammatory Syndrome in Children, MIS-C
See Also
Covid19
Kawasaki Disease
Epidemiology
First identified during Spring 2020 with onset of
Covid19
pandemic
Age
Initially identified in children and unlike
Kawasaki Disease
(age <11 years) extended to age 21
Age range from 1 week to 21 years (median 7-9 years)
Has since been reported in adults
Morris (2020) MMWR Morb Mortal Wkly Rep 69:1450-56 [PubMed]
https://www.cdc.gov/mmwr/volumes/69/wr/mm6940e1.htm
Gender
Boys represent 60% of cases (similar to
Kawasaki Disease
)
Race (U.S.)
Hispanic or Latino: 32%
Non-Hispanic Black: 30%
Pathophysiology
Systemic inflammatory condition as a complication of
COVID-19
, and similar to
Kawasaki Disease
Indications
Evaluation for MIS-C
Suspected or confirmed
COVID-19
within prior 4 weeks AND
Fever
>3 days AND
No other apparent explanation AND
Two or more of the following systems involved (or unexplained
Fever
>5 days)
Gastrointestinal findings (80% of patients)
Abdominal Pain
Diarrhea
Nausea
or
Vomiting
Neurologic findings (20% of patients)
Headache
Irritability
Lethargy
Altered Mental Status
Neurologic deficits
Head and Neck Symptoms
Conjunctivitis
(40%)
Cough
Congestion
Pharyngitis
Oral Lesion
s or other oral changes
Red Cracked Lips (23%)
Strawberry
Tongue
(4.5%)
Cervical Lymphadenopathy
(4%)
Swelling of hands or feet
Urethritis
Arthralgia
s or
Arthritis
Dermatologic findings
Polymorphic rash
Scaling
or peeling of skin (
Exfoliative Dermatitis
)
Labs
Background
Inflammatory markers are typically higher than in
Kawasaki Disease
First-Line - Tier 1 Screening
Complete Blood Count
with
Platelet
s and differential
White Blood Cell Count
increased (12-22k, mean 17k)
Associated with
Left Shift
(
Neutrophil
predominance) and lymphocytopenia
Contrast with only mildly elevated
White Blood Cell Count
s in
Kawasaki Disease
Anemia
(Hgb 8.3-10.3 g/dl, mean 9.2 g/dl)
Thrombocytopenia
(104-210 k/uL, mean 151 k/uL)
Contrast with
Thrombocytosis
in
Kawasaki Disease
Comprehensive metabolic panel
Electrolyte
s
Renal Function
tests
Liver Function Test
s
Serum Albumin
Levels 2.1 to 2.7 g/dl (mean 2.4 g/dl)
Contrast with normal
Serum Albumin
in
Kawasaki Disease
Inflammatory Markers
Erythrocyte Sedimentation Rate
C-Reactive Protein
Levels 16 - 34 mg/dl (mean 22 mg/dl)
Covid19
Test (typically nasopharyngeal PCR)
First-Line - Tier 2 Screening
Indications for Tier 2 tests (from Tier 1 Screening)
C-Reactive Protein
or CRP >5 mg/L or
Erythrocyte Sedimentation Rate
or ESR >40 mm/h AND
At least one of the following
Absolute
Lymphocyte Count
<1000/ul
Platelet Count
<150,000/ul or >450,000/ul
Serum Sodium
<135 mmol/L
Absolute Neutrophil Count
<1000/ul or >15,000/ul
Hypoalbuminemia (e.g.
Serum Albumin
<3 g/dl)
Tier 2 Tests
INR and PTT
D-Dimer
Levels 2.1 to 8.2 ng/ml (mean 3.6 ng/ml)
Serum
Troponin
Levels 0.008 to 0.294 mcg/L (mean 0.045 mcg/L)
Contrast with typically normal serum
Troponin I
n
Kawasaki Disease
NT-BNP
Levels 174 to 10,548 pg/ml (mean 788 pg/ml)
Contrast with typically normal NT-BNP in
Kawasaki Disease
Urinalysis
(and consider
Urine Culture
)
Blood Culture
Additional Testing to consider (based on
Consultation
, risk factors)
Fibrinogen
Factor VIII
and Von-Willebrand profile
Antithrombin III
Procalcitonin
Serum Ferritin
Levels 359 to 1280 ng/ml (mean 610 ng/ml)
Serum Triglyceride
s
Total IgG
Mycoplasma
PCR
Tick-Borne Illness
Serology
(e.g.
Lyme Disease
,
Babesiosis
,
Anaplasmosis
,
Rickettsia
- depending on region)
Antiphospholipid Antibody
profile and
Lupus Anticoagulant
Profile
Cytokine
Panel (e.g. IL1, IL6, IL8, TNFa)
Lactate Dehydrogenase
Uric Acid
Peripheral Smear
Diagnostics
Electrocardiogram
ST Segment
Changes
Premature Beats
QTc Prolongation
Atrioventricular Block
Sustained
Arrhythmia
Echocardiogram
(suspected MIS-C)
Ventricular dysfunction in 30% of cases (rare in
Kawasaki Disease
)
Coronary Artery
dilatation and aneurysms
Imaging
First-Line
Chest XRay
Differential Diagnosis
Multisystem Infammatory Syndromes
Covid19
Kawasaki Disease
Other Infections
Toxic Shock Syndrome
Septic Shock
Mycoplasma pneumonia
Viral Infection
s (e.g.
Adenovirus
, other Enteroviruses)
Measles
Tick-Borne Illness
Leptospirosis
Rheumatic Fever
Rheumatologic Condition
s
Vasculitis
Systemic Lupus Erythematosus
(SLE)
Juvenile Idiopathic Arthritis
Macrophage
Activation Syndrome
Hemophagocytic lymphohistiocytosis
Adverse Drug Reaction
See
Serious Cutaneous Adverse Reaction
Stevens-Johnson Syndrome
Drug Reaction with Eosinophilia and Systemic Symptoms
(
DRESS Syndrome
)
Miscellaneous
Malignancy
Management
Indications for Inpatient Evaluation and Management
Cardiac involvement
Hypoxia
Dehydration
Lymphocyte
s <1000/ul
Platelet
s <150k or >450k
C-Reactive Protein
or CRP >30 mg/L
Erythrocyte Sedimentation Rate
or ESR >40 mm/h
Serum Albumin
<3 g/dl
Significant
Anemia
for age
Coagulopathy
Management
Gene
ral
See
Covid19
for respiratory management
Multispecialty
Consultation
(Infectious disease, hematology and oncology, cardiology, rheumatology)
Immunomodulatory agents, antiplatelet agents and
Anticoagulation
per
Consultation
Intravenous Immune Globulin (IVIG) 2 g/kg in single dose
Low dose
Aspirin
3-5 mg/kg/day
Consider
Systemic Corticosteroid
s
Consider Immunomodulator
Anakinra
(
Kineret
, IL-1 Receptor Antagonist)
Consider empiric antibiotics when
Septic Shock
is considered in differential diagnosis
Ceftriaxone
(or if
Immunocompromised
, Cefepime) AND
Consider
Vancomycin
(if
Septic Shock
,
Meningitis
,
Central Line
) AND
Consider
Metronidazole
(if suspected abdominal source of infection) AND
Consider
Doxycycline
(if suspected
Tick Borne Illness
)
Complications
Hypotension
or
Shock
More common in MIS-C than in
Kawasaki Disease
Resources
Children's Hospital of Philadelphia MIS-C Evaluation Protocol
https://www.chop.edu/clinical-pathway/multisystem-inflammatory-syndrome-mis-c-clinical-pathway
Multisystem Inflammatory Syndrome (CDC)
https://www.cdc.gov/mis/hcp/index.html
American College of Rheumatology
https://www.rheumatology.org/Portals/0/Files/ACR-COVID-19-Clinical-Guidance-Summary-MIS-C-Hyperinflammation.pdf
References
(2020) University of Minnesota Masonic Guidance on Emergency Management MIS-C in Children
Darby (2021) Am Fam Physician 104(3): 244-52 [PubMed]
Jiang (2020) Lancet Infect Dis [PubMed]
https://www.thelancet.com/action/showPdf?pii=S1473-3099%2820%2930651-4
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