Table 6.
MIS-C workup and treatment
| Pediatric Organization | American College of Rheumatology220 | American Academy of Pediatrics222 | PIMS-TS National Consensus Management Study Group221 |
|---|---|---|---|
| Children presenting with unremitting high fever, an epidemiologic link to SARS-CoV-2 and suggestive clinical symptoms of MIS-C | Persistent fever (≥3 d) without a clear clinical source accompanied by symptoms concerning in their severity or coincident with recent exposure to a person with COVID-19 | Children presenting to the hospital with fever, abdominal pain, gastrointestinal, respiratory or neurologic symptoms who are stable | |
| Laboratory studies | Tier 1: Complete blood cell count with differential, complete metabolic panel, ESR, CRP, and testing for SARS-CoV-2 (by PCR or serology); If ESR or CRP are elevated and at least 1 other laboratory feature: lymphopenia, neutrophilia, thrombocytopenia, hyponatremia, or hypoalbuminemia, then proceed to tier 2; Tier 2: includes cardiac assessment and markers of systemic inflammation, which may include D-dimer, ferritin, procalcitonin, LDH, cytokine panels (including IL-6, tumor necrosis factor, or IL-10), and Cardiac laboratory values: troponin, B-type natriuretic peptide; a peripheral blood smear for assessment of microangiopathic changes can be considered |
Initial: Complete blood cell count with differential, urine analysis, ESR, and CRP Subsequent studies based on initial clinical suspicion or evidence of inflammation: Ferritin, LDH, comprehensive metabolic panel, proBNP, troponin, and fibrinogen In addition to the above, hospitalized children should also obtain triglycerides, creatinine kinase, amylase, blood and urine culture, D-dimer, prothrombin time/partial thromboplastin time, INR, SARS-CoV-2 PCR and SARS-CoV-2 serology (before the administration of IVIG) In severely ill-appearing or hemodynamically fragile patients, laboratory testing should be obtained regardless of duration of fever |
Initial: Full blood count, CRP, urea, creatinine, electrolytes, and liver function Second line (done within 12 h of admission): blood gas and lactate, fibrinogen, ferritin, D-dimer, troponin, NT-proBNP, LDH, SARS-CoV-2 RT-PCR test, and SARS-CoV-2 serology, septic and viral screen (lumbar puncture only if specifically indicated) |
| Imaging | Echocardiogram; cardiac computed tomography should be considered in patients with suspected distal coronary artery aneurysms not well visualized on echocardiogram | Chest radiograph, consider echocardiogram and/or cardiac MRI under consultation with pediatric cardiology | Done within 12 h of admission: chest radiograph; echocardiogram (daily in those who are physiologically unstable) Abdominal ultrasound to rule out alternative diagnoses |
| Other studies | ECG every 48 h; telemetry in those with conduction abnormalities | ECG | ECG |
| Treatment | Depending on the severity of symptoms, in addition to supportive care, the following therapies are recommended: First tier: IVIG (2 g/kg) should be given to patients with MIS-C who are hospitalized and/or fulfill KD criteria; Adjunctive: low to moderate dose steroids can be considered in children with milder forms of MIS-C who are persistently febrile and symptomatic despite IVIG; low to moderate dose glucocorticoids should be used with IVIG in those with severe or refractory disease; high and pulse dose glucocorticoids can be considered in those who do not respond to IVIG and low to moderate dose glucocorticoids Refractory disease: Anakinra (>4 mg/kg per d) can be considered in those refractory to IVIG and glucocorticoids. Low-dose aspirin (3–5 mg/kg per d) should be used until normalization of platelet count and normal coronary arteries at ≥4 wk after diagnosis (except in those with active bleeding, risk of bleeding, or platelet count ≤80,000/μL) Patients with MIS-C with coronary artery aneurysm with z-score ≥10 should be treated with low-dose aspirin and therapeutic anticoagulation with enoxaparin or warfarin |
IVIG (2 g/kg with max of 100 g) In patients who do not improve either clinically or by laboratory values, additional treatment can include steroid therapy (2–30 mg/kg per d of methylprednisolone depending on illness severity) and biologics (anakinra, 2–10 mg/kg per d, subcutaneously or intravenously, divided every 6–12 h) All patients with MIS-C should be started on low-dose aspirin (except for those with platelets < 100,000 or active bleeding) |
Continue treatment for presumed sepsis until microbiological cultures are available and preferred enrollment in a clinical trial for additional therapies; in the absence of a clinical trial, then the following was recommended: Children with KD-like phenotype (fulfills complete or incomplete KD criteria): First line: IVIG (2 g/kg single or divided dose) is recommended and a second dose can be considered for children who partially responded or have not responded at all to the first dose; Second line: methylprednisolone is recommended (10–30 mg/kg per d for 3 d) 24 h after IVIG if child remains unwell; given at the same time as IVIG in high-risk children (eg, age <12 mo and those with coronary artery changes) Third line: biological therapy is recommended with infliximab as biological therapy of choice for KD-like phenotype Children with nonspecific presentation and evidence of coronary artery abnormality, meeting criteria for toxic shock syndrome, evidence of progressive disease or extended duration of fever >5 d: First line: IVIG (2 g/kg single or divided dose) is recommended and a second dose can be considered for children who partially responded or have not responded at all to the first dose; Second line: methylprednisolone is recommended (10–30 mg/kg per d for 3 d) Third line: biological therapy is recommended (may include anakinra, infliximab, and tocilizumab) All children <12 y should wear compression stockings Follow local KD guidelines for aspirin dosing and continued for a minimum of 6 wk Follow local protocols for children with a thrombotic event Discuss with hematologist regarding long-term antiplatelet and anticoagulation therapy in children with abnormal coronary arteries |
| Follow-up | Echocardiogram: 7–14 d then 4–6 wk after presentation; consider 1 y echocardiogram in those with cardiac abnormalities Cardiac MRI at 2–6 mo in those with moderate to severe left ventricular dysfunction ECG: at each follow-up; consider a Holter monitor in those with conduction abnormalities |
Close follow-up 1–2 wk after discharge with pediatric cardiology and, if steroids or biologics were used, pediatric rheumatology | Recommended follow-up at 1–2 wk and 6 wk after discharge with echocardiography; multidisciplinary follow-up with pediatric infectious disease, immunology, and cardiology in those with coronary artery abnormalities or who have required organ support |
Abbreviations: CRP, C-reactive protein; ECG, electrocardiogram; ESR, erythrocyte sedimentation rate; IL, interleukin; INR, international normalized ratio; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MIS-C, multisystem inflammatory syndrome in children; NT-proBNP, N-terminal pro brain natriuretic peptide; PCR, polymerase chain reaction; PIMS-TS, pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2; RT-PCR, reverse-transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory distress syndrome coronavirus 2.