Clinic MIS-C: Clinic-Diagnostic/Dispo recs for Suspected Multisystem Inflammatory

GUIDELINE Syndrome in Children (Age <21 years)

A i m: T o standardize MIS-C m anagement based upon best available ev idence.

Pa t ients with a ll of t he following: EXCLUSION GUIDELINES
• Fev er > 38.0C Pa t ients wi th alternate probable
• A t least 2 suggestive clinical features •
Hist ory, exam + v ital signs (VS) inc. BP et i ology of illness. DDx i n cludes:
(r ash, GI sy mptom s, hand/foot edem a, • O2 t o k eep sats > 9 0 Bacterial sepsis, toxic shock syndrome,
• Con sider and investigate a lternate etiologies as indicated Kawasaki Di sease (KD), appendicitis,
con junctivitis, mucosal changes, Hem oph agocytic Lymphohistiocytosis
ly m phadenopathy, neurological Categorize patient
(HLH) or Macroph age Activation
ch anges), see page 7. Sy n drom e (MAS), rickettsia, v iral
• Ma y also have link t o COVID, see Note 1 . sy n drome (CMV , EBV, Adenovirus,
Coxsackie, varicella, etc.), bacterial
en teritis, lupus, vasculitis.

Pa t ient stable:
A n y instability including:
• Rea ssuring V S for age
• Low BP, t achycardia, or tachypnea for age
• T olerating PO
• In cr eased work of breathing or O2 sat < 9 0%
• W ell-appearing
• Poor per fusion or altered m ental status
• Ill-a ppearing
• Un a ble to m aintain hydration by PO
• Obt a in T ier 1 l abs: SARS CoV-2 PCR and serology, CBC w/
diff, CRP, ESR, CMP. Additional t ests if indicated per sy mptom s
(e.g. strep swab).

Do t h e labs sh ow a ll of the following?

1. CRP ≥ 5 m g/dL OR ESR ≥ 40 mm/hr T r ansfer t o ED for possible MIS-C
MIS-C n ot su spected Ch ildren’s Physician Access:
2. At least 1 additional suggestive lab abnormality Yes
Ma n age off-guideline, re- No 6 1 2-343-2121
• ALC <1000/ul
ev aluate if sy mptom s do
• Platelets < 150,000/ul
n ot im prov e in 1 -2 days
• Na < 135 mmol/L
• Neutrophilia (ANC > 7,700)
• Albumin < 3
PLUS No alternate probable diagnostic
explanation for symptoms and lab findings Not e 1. Link includes A NY of t he following criteria: +
COV ID PCR or serology, preceding illness r esembling
COV D‐1 9, or close contact with confirmed or suspected
COV ID‐1 9 cases in the past 4-6 weeks. Link is not required
for MIS-C diagnosis.

Disclaimer: This guideline is designed for general use with most patients; each clinician should use his or her own independent judgment to meet the needs of each individual patient. This guideline is not a substitute
Rev i ewer: Workgroup
for professional medical advice, diagnosis or treatment. Rev i sed 2/2021
 MIS-C: ED-Diagnostic/Dispo recs for Suspected Multisystem Inflammatory
ED Syndrome in Children (MIS-C) Associated with COVID-19
GUIDELINE
(Age <21 years)

Pa t ients with a ll of t he following: EXCLUSION GUIDELINES

• Fev er > 38.0C Pa t ients wi th alternate probable etiology of
• A t least 2 suggestive clinical features (rash, i llness. DDx i ncludes: Bacterial sepsis, toxic
GI sy m ptom s, hand/foot edema, • Hist ory, exam + v ital signs (VS) including BP sh ock syndrome, Kawasaki Di sease (KD),
con junctivitis, mucosal changes, • O2 t o k eep sats > 9 0 appen dicitis, HLH/MA S, rickettsia, viral
ly m phadenopathy, neurological changes), • Con sider and investigate a lternate etiologies as indicated sy n drome (CMV , EBV, Adenovirus, Coxsackie,
see pa ge 7. Categorize patient v aricella, etc.), bacterial enteritis, lupus, vasculitis.
• Ma y have link to COVID ~ 4 -6 weeks prior,
see n ot e 1 page 1 .
aLaboratory T iers

Work up other etiologies as indicated.

 T i er 1: SARS CoV-2 PCR and
Pa t ient well-appearing w/ n ormal V S Pa t ient ill-appearing; hypotension, poor perfusion, signs of ser ology, CBC w/ diff, CRP, ESR,
a side from fev er sepsis, toxidrom e/toxic shock, or with KD cr iteria CMP. A dditional tests if indicated
per sy mptoms (e.g. strep swab).
 T i er 2: blood culture, UA/UCx,
la ctate, blood gas, procalcitonin,
• Obt ain T ier 1 labsa (ED su spected MIS-C or derset). ser um t o save, Ig G, IgA, Ig M, BNP,
• A dd T ier 2 labs if h igh clinical suspicion for MIS-C. • St a bilize patient: PIV, fluid resuscitate (caution with boluses)
t r oponin, LDH, CPK, D Dim er, PT,
• A dd CXR if resp symptom s. • A dd CXR if resp symptom s. Consider abdominal US if sev ere
PT T , Fibrinogen, ferritin, T G, type
a bdom inal pain or prolonged fever of unclear source.
a n d cross, cytokine storm and
• Obt ain T ier 1 & 2 labs. Add Tier 3 if t oxin-m ediated suspected.
cy tokine inflammation panels,
• Con sult ID.
MRSA n asal swab.
Do T i er 1 l abs show all of t he following? • Con sider other guidelines/order-sets (e.g. sepsis, KD)
 T i er 3: V aginal swab for Group A
1. CRP ≥ 5 m g/dL OR ESR ≥ 40 mm/hr St r ep and Staph aureus (order
2. At least 1 of the follow ing "Gen ital culture").
• ALC <1000/ul • A dd T ier 2 labsa if
• Platelets < 150,000/ul Yes n ot y et obtained.
• Na < 135 mmol/L
• Neutrophilia (ANC > 7,700) MIS-C Su spected, Complete
• Albumin < 3 a dditional workup:
PLUS No alternate probable diagnosis. La bs su ggestive of MIS-C? • CX R, EKG. Get ECHO in ED on ly if
Mos t patients have ≥ 4 abnl m arkers of inflammation h em odynamic instability.
• Ev i dence of i nflammation: CRP > 5 mg/dL, • Ca ll ID fr om ED.
No ESR > 4 0 m m/h, ferritin > 5 00 ng/m L, ANC > • PICU if a ny signs of cardiac dysfxn (abnl
Yes EKG or t r oponin- obtain result before
7 7 00, ALC < 1 000, platelet < 1 50k, D-Dim er > 2
m g /L, fibrinogen > 4 00 mg/dL, a lbumin < 3 g /dL, t r ansfer), shock/hypotension, high r esp
MIS-C n ot su spected. Ma nage off- a n em ia, ALT > 4 0 U/L, INR > 1 .2 su pport, or concern for rapid
No
g u ideline, re-evaluate if sy mptom s do • Ot h er: AKI, hyponatremia, high LDH, high pr ogression
n ot im prov e in 1 -2 days t r oponin, BNP > 4 00 pg/m L, prolonged PT or PTT • Med-Su rg if not m eeting PICU criteria

Disclaimer: This guideline is designed for general use with most patients; each clinician should use his or her own independent judgment to meet the needs of each individual patient. This guideline is not a substitute
Rev i ewer: Workgroup
for professional medical advice, diagnosis or treatment. Rev i sed 2/2021
 MIS-C: ICU Management: Patients meeting ICU criteria (any cardiac
ICU
GUIDELINE dysfunction or shock and/or sepsis)
(Age <21 years)

Init ial ICU Management Not e 1. Refractory or rapidly

• Echo: obtain after admission. Telemetry x 72 hours or until cardiology discontinues. pr ogr essive di sease
• Empiric antibiotics as appropriate for clinical presentation (e.g. vancomycin, ceftriaxone, and • “ Refractory” is defined in ACR guidelines as
clindamycin for community-acquired shock) until cultures negative for 48 hour or as-directed by ID. per sistent fev ers and/or ongoing and
sig n ificant end organ involvement. T iming
• Consults: ID, Im munology and Cardiology for all ICU patients. Hematology if questions not addressed on
of fev er in relation t o IVIG is not defined.
guideline. Endocrine 2 days prior to discharge for patients on steroids anticipated > 3 weeks.
For Ka wasaki Disease this has been 36
• IVIG: Giv e 2 g/kg x 1 (use ideal body weight)- See Note 1 for repeat dose. In patients with cardiac
h ou rs A FTER com pletion of IVIG.
dy sfunction, IVIG m ay be given in divided doses (1 g/kg/day over 2 days).
• Discu ss treatment options with
• St eroids: Give methylprednisolone IV 2 mg/kg/day (max 6 0 mg/day), or bolus may be needed- See Note 1. con sultants.
• Aspirin- use low-dose (3 -5 m g/kg/day with max dose of 81 m g/day) in MIS-C (including if KD features) • Repea ting IVIG is not recom mended,
unless platelet count is < 80,000 (as guided Cardiology). Note, ok to use prophylactic enoxaparin with low- t h ough should also be discussed with
dose aspirin (which adds anti-platelet and coronary artery protection). con sultants if presentation more sim ilar to
• VTE prophylaxis unless contraindication (see COVID VTE guideline) until hospital discharge. KD.
• Therapeutic Anticogaulation: • For m ost severely ill children, bolus
o Patients with CAA z-score of ≥ 5 should be treated with low-dose aspirin and therapeutic anticoagulation m ethylprednisolone 10-30 m g/kg/day IV
with enoxaparin (factor Xa level 0.5–1.0) or warfarin. (m ax 1,000 m g/day)
o Patients with EF < 35% or documented thrombosis should be treated with therapeutic anticoagulation • In s ome cases anakinra 2-1 0 m g/k g/dose
alone (no aspirin needed). (m ax 1 00 mg/dose) SQ/IV q6-1 2h may be
• GI prophy laxis until off steroids. needed.
• Rev isit differential diagnosis.
Trending of Labs and EKGs in ICU patients
• CBC w/ diff, CRP, BMP, d-dimer, ferritin Q day until afebrile and labs improving x 3 days
• Troponin Q6 hr, decrease as indicated
• BNP Q4 8 hr or sooner if clinical worsening
• Repeat other labs as indicated
• EKG Q4 8 hrs to monitor QT interval, or sooner if clinical worsening

Repeat inpatient Echo frequency

• Init ial normal: 1-2 weeks and 4 -6 weeks
• Init ial abnormal with CA z-score >2.5: repeat Q 2 -3 days until CA aneurysm stable, then weekly until
discharge.
• Repeat echo earlier if clinical worsening

Transfer t o Med-Surgunit once meeting criteria

• No ongoing cardiac dysfunction or shock
• Norm alized troponin
• Respiratory support at levels allowed on m ed-surg unit

Disclaimer: This guideline is designed for general use with most patients; each clinician should use his or her own independent judgment to meet the needs of each individual patient. This guideline is not a substitute
Rev i ewer: Workgroup
for professional medical advice, diagnosis or treatment. Rev i sed 2/2021
 Med-Surg MIS-C: Med-Surg Management for patients identified as having MIS-C
GUIDELINE (Age <21 years)

Init ial Med-Surg Management: Pa tients not m eeting ICU criteria (any cardiac dysfunction or shock and/or
Not e 1. Di sease Severity
sepsis). Note, if patient m eets classic Kawasaki Disease criteria, consider KD g uideline if n o other MIS-C features.
• Not w ell defined in literature
• Echo: obtain after admission. Telemetry x 24 hours or until cardiology discontinues.
• Mi l d: Bor derline or m ild case. Normal VS a part
• Fluids: resuscitate in 10 ml/kg aliquots with re-evaluation after each bolus. Maintain euvolemia. fr om fever, n o inpt criteria other t han poor PO,
• Empiric antibiotics as appropriate for clinical presentation (e.g. ceftriaxone and m etronidazole for m ild dehydration, or m onitoring for worsening
possible appendicitis; ceftriaxone for possible pyelonephritis) until cultures negative for 4 8 hour or as- • Moder a te: Meets case definition without shock
directed by ID. or ot h er ICU criteria
• Consults: ID: for all patients. Immunology: ID to contact Im munology as needed. Cardiology: for all • Sev ere: Meets case definition and any ICU
patients with cardiac abnormalities or refractory disease. Hematology: if questions not addressed on cr iteria: ill-appearing, ev idence of or gan
guideline. Endocrine: 2 days prior to discharge for patients on steroids anticipated > 3 weeks. Goal is daily dy sfunction/injury, require for respiratory or
group rounding call with active consultants. ca rdiov ascular support
• IVIG: Giv e 2 g/kg x 1 (use ideal body weight)- See Note 1 and 2.
• St eroids: Methylprednisolone 2 m g/kg/day (max 60 mg/day) should be given to patients who are Not e 2. Refractory disease
collaboratively determined with ID and Immunology to have moderate MIS-C. Discuss steroid use with ID • Defin ed in ACR guidelines as persistent fevers
(and Im munology if also consulted) in patients for whom the diagnosis of m ild MIS-C is being considered. a n d/or ongoing and significant end organ
All patients with severe disease (ICU) should receive steroids. See Notes 1 and 2. See page 7 for weaning and in v olvement. T iming of fever in relation t o IV IG
follow-up. is n ot defined. For Kawasaki Disease this has
• Aspirin- use low-dose (3 -5 m g/kg/day with max dose of 81 m g/day) in MIS-C (including if KD features) been 36 hours AFTER com pletion of IV IG.
unless platelet count is < 80,000 (as guided Cardiology). Note, ok to use prophylactic enoxaparin with low- • Discu ss treatment options with consultants.
dose aspirin (which adds anti-platelet and coronary artery protection). • Repea ting IVIG is not recom mended, though
• VTE prophylaxis unless contraindication (see COVID VTE guideline) until hospital discharge. sh ou ld also be discussed with consultants if
pr esentation more similar to KD.
• Therapeutic Anticoagulation: Patients with CAA z-score of ≥ 5 should be treated with low-dose aspirin
• For m ost severely ill children, bolus
and therapeutic anticoagulation with enoxaparin (factor Xa level 0.5–1.0) or warfarin. Patients with EF <
m ethylprednisolone 10-30 m g/kg/day IV (max
3 5% or documented thrombosis should be treated with therapeutic anticoagulation alone (no aspirin 1,000 m g/day).
needed). • In s ome cases anakinra 2-1 0 m g/k g/dose (max
• GI prophy laxis until off steroids. 1 0 0 mg/dose) SQ/IV q6-1 2h may be needed.
Trending of Labs and EKGs in Med-Surg patients, by disease severity (see Not e 1) • Rev isit differential diagnosis.
• Mild: CBC w/ diff, CRP, BMP, d-dimer, ferritin Q day until afebrile and labs improving x 1 day then may do • Con sider PICU transfer.
PRN for clinical worsening. Repeat troponin and BNP if clinical worsening/persistent fever. EKG Q4 8 hr.
• Moderat e: CBC w/ diff, CRP, BMP, d-dimer, ferritin Q day until afebrile and labs improving x 3 days then Di sch arge cr iteria:
m ay do PRN for any clinical worsening. Repeat troponin Q6 hr until normalized and BNP Q 4 8 hr- repeat • CRP, ferritin, and d-dimer im prov ing
cardiac markers sooner if clinical worsening or persistent fever. Non-urgent cardiology consult if increasing • A febrile x 48 h ours
cardiac markers. EKG Q4 8 hours to m onitor QT. Im munology service to advise on timing of repeat • Blood cu ltures without growth x 48 hours
cy tokine panels if indicated. • EKG w ithout arrhythmia
Repeat inpatient Echo frequency • La t est echo stable/im prov ed
• Init ial normal: 1-2 weeks and 4 -6 weeks • T olerating enteral diet
• Init ial abnormal with CA z-score >2.5: repeat Q 2 -3 days until CA aneurysm stable, then weekly until • Not r equiring oxygen
discharge. • Follow -up coordinated
• Repeat echo earlier if clinical worsening
Disclaimer: This guideline is designed for general use with most patients; each clinician should use his or her own independent judgment to meet the needs of each individual patient. This guideline is not a substitute
Rev i ewer: Workgroup
for professional medical advice, diagnosis or treatment. Rev i sed 2/2021
 MIS-C: Med-Surg Management for patients with mild disease not yet meeting
Med-Surg
GUIDELINE
case definition for MIS-C
(Age <21 years)

Init ial Med-Surg Management: Change to full management page of guideline if case definition is met.
• Echo: obtain non-urgently after admission. Not e 1. Di sease Severity
• Neuroimaging: Consider if neurological changes concerning for clot/stroke. • Not w ell defined in literature
• Fluids: resuscitate in 10 ml/kg aliquots with re-evaluation after each bolus. Maintain euvolemia. • Mi l d: Bor derline or m ild case.
Nor m al VS a part from fever, n o inpt
• Consults: ID for all patients. ID attending will discuss case with Immunology if indicated.
cr iteria other than poor PO, m ild
• VTE prophylaxis- see COVID VTE guideline to determine if patient meets criteria.
dehy dration, or monitoring for
• In v estigate alternate potential etiol ogies. Differential diagnosis for MIS-C is broad and includes bacterial sepsis,
w or sening
t ox ic shock sy ndrom e, Kawasaki Disease, appendicitis, HLH/MAS, rickettsia, viral sy ndrom e (CMV, EBV , Adenovirus,
• Moder a te: Meets case definition
Cox sackie, v aricella, etc.), bacterial enteritis, SLE, vasculitis and other diseases.
w ithout shock or other ICU criteria
• Sev ere: Meets case definition and
Trending of Labs and EKGs in Med-Surg patients with mild disease (see Not e 1) who do not y et meet
a ny ICU criteria: ill-appearing,
MIS-C case definition and wit hout alternate diagnosis identified. ev idence of organ dy sfunction/injury,
• Mild: CBC w/ diff, CRP, BMP, d-dimer, ferritin Q day until afebrile and labs improving x 1 day then may do PRN r equ ire for respiratory or
for any clinical worsening. Repeat troponin and BNP if clinical worsening or persistent fever. EKG Q4 8 hours. ca rdiov ascular support
Repeat Echo if clinical worsening or cardiac markers become abnormal (change to full m anagement page).

Repeat l abs or evolution of symptoms suggestive of MIS-C wi t hout ot her likely cause? Di sch arge cr iteria:
Mos t patients have ≥ 4 abnl m arkers of inflammation • CRP, ferritin, and d-dimer im prov ing or
• Ev i dence of i nflammation: CRP > 5 mg/dL, ESR > 4 0 m m/h, ferritin > 5 00 ng/m L, ANC > n ot m eeting MIS-C thresholds
7 7 00, ALC < 1 000, platelet < 1 50k, D-Dim er > 2 mg/L, fibrinogen > 4 00 m g/dL, albumin < 3 g/dL, • A febrile
a n em ia, ALT > 4 0 U/L, INR > 1 .2 No
• Blood cu ltures without growth x 24 hr, if
• Ot h er: AKI, hyponatremia, high LDH, high troponin, BNP > 4 00 pg/m L, prolonged PT or PT T a pplicable
• Sy m ptoms: Fev er > 38.0C, epidemiologic link to SARS-CoV-2 infection (not required), and a t • EKG w ithout arrhythmia
lea st 2 suggestive clinical features (rash, GI symptom s, hand/foot edema, conjunctivitis, m ucosal • T olerating enteral diet
ch anges, lymphadenopathy, neuro changes), see page 7. • Not r equiring oxygen
• Follow -up with PCP

Yes

MIS-C Su spected
• CX R, EKG
• Refer t o guideline page 4 for full management

Disclaimer: This guideline is designed for general use with most patients; each clinician should use his or her own independent judgment to meet the needs of each individual patient. This guideline is not a substitute
Rev i ewer: Workgroup
for professional medical advice, diagnosis or treatment. Rev i sed 2/2021
 CLINICAL MIS-C: Post-Hospital Care
GUIDELINE (Age <21 years)

A i m: T o standardize MIS-C m anagement based upon best available ev idence.

In i tial Follow-up Plan

• Follow up with PCP in 2-3 days. Only repeat labs if they had not normalized prior t o discharge. Labs include CRP, CBC w/ differential, BNP, T roponin, D-
Dim er. Labs can then be r epeated if the patient dev elops any recurrence of fev er/rash/GI symptom s during the steroid wean. For patients who stay asymptomatic,
la bs should be repeated again prior to transition t o hydrocortisone (if applicable).
• Follow -up with cardiology 1-2 weeks after discharge with r epeat EKG and Echo
• Follow -up with En docrinology via t elehealth 2 weeks after steroids started (if anticipated duration ≥ 3 weeks), see below.
• Follow -up 4-6 weeks with cardiology with Echo, consider cardiac MRI 1 -3 months
• Disch arge medications: low-dose aspirin until Cardiology discontinues, and gastritis prophylaxis until off st eroids. Patients will n ot routinely be discharged on
a n ticoagulation (aside from aspirin).
• If st eroids were used, im munology will a dvise on the duration of the acute wean (generally 2-3 weeks if m ilder, 4-8 week s on a case-by-case basis with im munology
in v olvement in more sev ere cases). Primary team will calculate and prescribe the wean doses and steps as part of discharge plan (see page 7). Endocrine will follow
pa t ients n eeding ≥ 3 weeks of st eroids with a telehealth appointment 2 weeks a fter st eroids were started in order t o plan the stress wean and ACTH st im test.
En docrinology will not be r esponsible for adjusting st eroids in response to r ecurrence of MIS-C clinical symptom s or lab changes.

Wh en to con sider r eadmission?

• A ny recurrent fever or other recurrence of sy mptom s (rash, mucositis, conjunctivitis, vom iting/diarrhea, neurological changes, chest pain, etc.) sh ould prom pt
u r gent ev aluation by prim ary prov ider. If patient is stable and can be assessed by outpatient prov ider within 6-1 2 h ours t hat m ay be considered. Otherwise r efer
pa t ient t o local ED (if > 6 0 m inutes away) or t o Children’s Minnesota ED.
• If seen in primary clinic with r ecurrence of sy mptom s, obtain full exam + V S including BP. If u nstable transfer t o Children’s Minnesota ED. If st able and n o
a lt ernate source of illness is suspected, may obtain labs: CBC w/ diff, CRP, ESR, ferritin, procalcitonin, CMP. Consider: troponin, d-dimer, UA, Urine Culture, Blood
Cu lture, Rapid Strep. Outpatient prov iders should contact ID/immunology t o discuss whether re-ev aluation at Children’s Minnesota is needed. W orsening
la boratory m arkers (e.g. increasing CRP) in absence of clinical signs should prom pt outpatient discussion with specialists (ID, immunology, cardiology, h ematology
depending on the laboratory study).
• Ca ll Children’s Minnesota Physician’s A ccess 866-7 55-2121 t o be connected with specialists on call and/or ED.

Edu cation for Family

• A v oid NSAIDs while on aspirin
• No liv e-v irus vaccines x 11 m onths if IV IG was given (pts at high ris k of exposure may receive s ooner and be reimmuniz ed after 11 m onths if they have an
inadequate s erological response).
• Risk s of IV IG including: hemolytic anem ia, aseptic meningitis
• Discu ss plan for r ecurrent fever or ot her KD sy mptom s (rash, mucositis) with family — r ecom mend any sy mptom s be ev aluated by PCP or ED A SAP.
• Fa m ilies should receive t eaching on stress dose st eroids.
• Lim it exercise and strenuous activity until cleared by cardiology (anticipate several m onths)

Disclaimer: This guideline is designed for general use with most patients; each clinician should use his or her own independent judgment to meet the needs of each individual patient. This guideline is not a substitute
Rev i ewer: Workgroup
for professional medical advice, diagnosis or treatment. Rev i sed 2/2021
 CLINICAL MIS-C: Additional Notes
GUIDELINE

Di fferential Di agnosis for MIS-C includes bacterial sepsis, toxic shock sy ndrom e, Kawasak i Disease (KD), Clinical Features/Evidence of MIS-C
a ppendicitis, h emophagocytic ly mphohistiocytosis (HLH) or macrophage activation sy ndrom e (MAS), • Most patients have > 4 organ system
r ickettsia, viral sy ndrom e (CMV, EBV , Adenovirus, Coxsackie, v aricella, etc.), bacterial enteritis, lupus, involvement; > 2 required for diagnosis
v asculitis and other conditions. • Involvement of the following systems (percent
of patients in case series):
Or der sets: ED-fev er, ED-COVID, ED Suspected MIS-C, In patient Suspected MIS-C • Gastrointestional (92%)
• Cardiovascular (80%)
St er oid Dosi ng + T aper Suggestions (Di scuss with consultants and pharmacist) • Hematologic (76%)
• For m oderate/sev ere cases consider methylprednisolone 2 m g/k g/day (m ax 60 m g per day) then t aper ov er • Mucocutaneous (74%, 59% rash)
2 -3 weeks. • Respiratory (70%)
• For r efractory or rapidly progressive cases (see criteria on pages 3 or 4 ) methylprednisolone 1 0-30 • Musculoskeletal (23%)
m g /kg/day (max 1,000 mg/day) for 1-3 days, then 2 m g/kg/day (m ax 60 m g/day) and taper ov er 4-8 weeks • Renal (8%)
on a ca se-by-case basis with im munology involvement (re: acute wean) and En docrinology (re: stress • Neurologic (6%)
w ean). • Recent COVID illness OR exposure (note: not
• Or a l steroid therapy: Transition from IV m ethylprednisolone to oral prednisolone (liquid) or oral necessary to suspect MIS-C)
pr ednisone (tablet) u sing the following conversion: 4 mg methylprednisolone = 5 mg prednisolone or
pr ednisone Lab Evidence of MIS-C
T h e purpose of the prolonged st eroid t aper in MIS-C is prevention of r ebound inflammation. No lab criteria is diagnostic; most patients have 4
Gen eral guidance: or more markers of inflammation
•In it iate taper when patient has clinically im proved (e.g. off pressors, off r espiratory support, afebrile, down- • Evidence of inflammation, common values:
t r ending CRP) CRP > 3 mg/dL, ESR > 40 mm/h, ferritin > 500
•Redu ce st eroid dose by 1 0-1 5% ev ery 3 days while inpatient ng/mL, ANC > 7700, ALC < 1500, platelet <
•Redu ce st eroid dose by 1 5-25% ev ery 3-5 days while outpatient 150k, D-Dimer > 2 mg/L, fibrinogen > 400
•T a per should be guided by clinical response and inflammatory m arkers (e.g. fever, CRP) and will be managed mg/dL, albumin < 3 g/dL, anemia, ALT > 40
by primary provider. U/L, INR > 1.2
•Pa t ients receiving steroids for an anticipated duration of ≥3 weeks n eed to have an A CTH stim test. • Other: AKI, hyponatremia, high LDH, high
Hospitalist/Intensivist t o consult Endocrinology 2 days prior to discharge in these patients. troponin, BNP > 400 pg/mL, prolonged PT or
PTT

Clinical Features by Organ Sys tem Adapted from Feldstein LR, Rose EB, Horwitz SM, Collins JP,
Newhams MM, Son MBF, et al. Multisystem Inflammatory Syndrome in
• GI (a bdom inal pain, vom iting/diarrhea) U.S. Children and Adolescents. N Engl J Med [Internet]. 2020; Available
• CV (Chest pain, tachycardia) from: http://www.ncbi.nlm.nih.gov/pubmed/32598831
• Heme (cell line abnormalities, thrombosis)
• Res p (SOB, cough, tachypnea)
• Mucocutaneous (strawberry t ongue, cracked lips, sore throat, polymorphic rash)
• Extremity (hand/foot redness or swelling)
• Lymphadenopathy
• Neuro: (headache, irritable, a ltered mental status, CN palsy )

Disclaimer: This guideline is designed for general use with most patients; each clinician should use his or her own independent judgment to meet the needs of each individual patient. This guideline is not a substitute
Rev i ewer: Workgroup
for professional medical advice, diagnosis or treatment. Rev i sed 2/2021
 CLINICAL MIS-C: Additional Notes
GUIDELINE

A i m: T o standardize MIS-C m anagement based upon best available ev idence.

Refer ences/Resources:
• CDC’s 24-hour Emergency Operations Center: 770-488-7100.
• American College of Rheumatology Guideline
• Evelina London Clinical Guideline https://pubmed.ncbi.nlm.nih.gov/33277976/
• Royal College of Paediatricsand Child Health: https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf
• CDC: Health Alert Network (HAN) No. 432 –Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19)05/14/2020
• https://www.who.int/publications-detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19
• Viner and Whittaker. "Kawasaki-like disease: emerging complication during the COVID-19 pandemic." LancetMay 13, 2020
• Verdoniet al. "An outbreak of severe Kawasaki-like disease at the Italian epicentreof the SARS-CoV-2 epidemic" May 13, 2020 Lancet
• Toubianaet al., "Outbreak of Kawasaki disease in children during COVID-19 pandemic: a prospective observational study in Paris, France." medrix
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• NY Presbyterian Kids Clinical Guideline
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MIS-C Wor kgroup: Hester, Nowak, Garland, Pozos, Pom putius, Kalaskar, Koutsari, B. Chu, Bergmann, Wegmann, Sznewajs, Brunsberg, Lissick, Noble, Bom an,
Schultz, Wiplinger, Kuelbs, Derks, Singewald

Disclaimer: This guideline is designed for general use with most patients; each clinician should use his or her own independent judgment to meet the needs of each individual patient. This guideline is not a substitute
Rev i ewer: Workgroup
for professional medical advice, diagnosis or treatment. Rev i sed 2/2021