Multisystem Inflammatory Syndrome in Children (MIS-C)
Clinical Snapshot
Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious hyperinflammatory condition that typically develops 2-6 weeks after SARS-CoV-2 infection or exposure — often even when the preceding infection itself was mild, asymptomatic, or unrecognized — presenting with persistent fever, markedly elevated inflammatory markers, and dysfunction across multiple organ systems.[1][2]
Genuinely related to, but distinct from, Kawasaki disease. MIS-C shares real overlap with Kawasaki disease — overlapping mucocutaneous findings, and a shared core acute pharmacotherapy of IVIG and corticosteroids — but it is a separate diagnostic entity. MIS-C requires evidence of recent or current SARS-CoV-2 infection or exposure; it skews toward an older age group (median roughly 7-9 years versus classic Kawasaki disease's under-5 predominance); and it carries a substantially higher burden of gastrointestinal symptoms, myocardial dysfunction, and shock. A documented final diagnosis of Kawasaki disease should specifically be considered an alternative diagnosis and excluded from MIS-C classification.[2][3] See Assessment & Diagnosis for the full, explicit comparison.
The single most important evidence-based treatment shift in this chapter: IVIG 2 g/kg plus an upfront corticosteroid, started together, is now the preferred first-line approach — a real change from earlier practice that used IVIG alone and reserved corticosteroids for treatment failure. In a propensity-matched cohort, the combination reduced treatment failure from 38% (IVIG alone) to 9%, alongside less need for second-line therapy, less hemodynamic support, less post-treatment left ventricular dysfunction, and a shorter PICU stay.[4][5][6] Low-dose aspirin is given to essentially every patient for antithrombotic prophylaxis, reflecting MIS-C's hypercoagulable state, rather than the higher anti-inflammatory dosing used acutely in classic Kawasaki disease.[6] Biologic escalation (anakinra or infliximab) is reserved for IVIG/corticosteroid-refractory disease — and, importantly, refractory MIS-C is not routinely managed by simply repeating IVIG, given the volume-overload and hemolytic-anemia risk of a second large infusion in a population already prone to myocardial dysfunction.[5] Because shock occurs in a genuinely much larger share of MIS-C patients than classic Kawasaki disease, early recognition of hypoperfusion and a low threshold for critical-care involvement are central themes throughout this chapter.[3]
Recognize the Condition
Epidemiology and timing
MIS-C skews toward school-age children and adolescents — a median age of roughly 7-9 years, spanning as young as infancy to age 20 — a genuinely older distribution than classic Kawasaki disease, whose mean age is around 3 years, with roughly three-quarters of cases under age 5.[3] Onset typically follows SARS-CoV-2 infection or exposure by 2-6 weeks, and the preceding infection is frequently mild, asymptomatic, or entirely unrecognized by the family, which can make the temporal link easy to miss unless specifically asked about.[1]
Three clinical presentations
The Canadian Paediatric Society frames MIS-C as presenting in one of three overlapping patterns, useful for organizing the clinical picture: fever with hyperinflammation (persistent fever with elevated inflammatory markers, without a dominant mucocutaneous or shock picture), a Kawasaki-disease-like presentation (meeting or approaching the classic KD mucocutaneous criteria — conjunctival injection, oral changes, rash, extremity changes, lymphadenopathy), and a shock presentation (hypotension or poor perfusion, sometimes resembling toxic shock syndrome).[6] Gastrointestinal symptoms — abdominal pain, vomiting, diarrhea — are genuinely prominent across all three patterns, present in roughly 80% of MIS-C cases, and are comparatively uncommon in classic Kawasaki disease.[3]
The WHO preliminary case definition
The World Health Organization's original scientific brief established the syndrome's international case definition: children and adolescents with fever, elevated inflammatory markers, and evidence of single or multi-organ dysfunction, together with evidence of current or recent SARS-CoV-2 infection or a likely contact, and after other obvious microbial causes of inflammation have been excluded.[7] This preliminary framework remains broadly consistent with, but less granular than, the current CDC/CSTE surveillance definition below, which is the version used for the detailed criteria in this chapter.
The CDC/CSTE surveillance case definition (effective 2023)
All of the following are required, in the absence of a more likely alternative diagnosis:
| Required element | Definition |
|---|---|
| Age | Under 21 years |
| Fever | Subjective or documented fever, temperature ≥38°C — no minimum duration is required under the current definition, a change from the original 2020 CDC definition's fever-duration requirement |
| Severity | Clinical severity requiring hospitalization, or resulting in death |
| Systemic inflammation | C-reactive protein ≥3.0 mg/dL (30 mg/L) |
| Organ-system category (new-onset findings in ≥2 of 5 required) | Qualifying findings |
|---|---|
| Cardiac | Left ventricular ejection fraction <55%, coronary artery dilatation/aneurysm/ectasia, or troponin elevation |
| Mucocutaneous | Rash, oral mucosal inflammation, conjunctivitis, or extremity erythema/edema |
| Shock | Clinician documentation of shock |
| Gastrointestinal | Abdominal pain, vomiting, or diarrhea |
| Hematologic | Platelet count <150,000/µL, or absolute lymphocyte count <1,000/µL |
[2] SARS-CoV-2 evidence is required for a confirmed case (a positive molecular/NAAT or antigen test within 60 days before or during hospitalization, or SARS-CoV-2-specific antibodies associated with the current illness) or, for a probable case, close contact with a confirmed or probable COVID-19 case within the 60 days before hospitalization can substitute for direct laboratory evidence.[2] Important exclusion a documented final diagnosis of Kawasaki disease is specifically considered an alternative diagnosis under this definition — such cases should not be classified or reported as MIS-C, underscoring that these two conditions are meant to be distinguished, not conflated.[2]
Risk Factors
- Age: MIS-C skews toward school-age children and adolescents (median roughly 7-9 years), a genuinely older distribution than classic Kawasaki disease, which predominantly affects children under 5.[3]
- Timing: onset typically follows SARS-CoV-2 infection or exposure by 2-6 weeks, often even when the preceding infection itself was mild, asymptomatic, or unrecognized by the family.[1]
- Unvaccinated or incompletely vaccinated status against COVID-19 at the time of infection — vaccination reduces the risk of subsequent MIS-C, a genuinely useful point when counselling families who are hesitant about ongoing COVID-19 vaccination.[1]
- No single genetic or ethnic predisposition is established for MIS-C in the way East Asian ancestry is associated with classic Kawasaki disease; MIS-C's demographic pattern has differed across surveillance cohorts and continues to be actively studied.[3]
- A clinically convincing shock or Kawasaki-like presentation temporally linked to COVID-19 should itself be treated as a risk marker for MIS-C requiring urgent work-up, rather than waiting for additional risk factors to accumulate.[6]
Red Flags & Refer
Given MIS-C's substantially higher shock rate than classic Kawasaki disease, this entire chapter is oriented around urgent recognition and a low threshold for escalation. Refer/escalate immediately for:
- Any child or adolescent with persistent fever plus multisystem involvement in a plausible temporal relationship to COVID-19 (current or within the preceding roughly 6 weeks) — do not wait for definitive SARS-CoV-2 laboratory confirmation before arranging urgent assessment in a clinically convincing, probable case.[2]
- Any sign of hypoperfusion or shock — cool extremities, delayed capillary refill, tachycardia out of proportion to fever, hypotension, or altered mental status — which occurs in a substantially higher share of MIS-C patients than in classic Kawasaki disease and needs emergency-level evaluation, not outpatient reassurance.[3]
- Signs suggesting myocardial dysfunction — chest pain, syncope, poor perfusion, a new gallop or murmur, or respiratory distress — evaluate emergently with echocardiography, ECG, troponin, and BNP/NT-proBNP.[1]
- Severe or worsening abdominal pain: given how common and how prominent GI symptoms are in MIS-C (roughly 80% of cases), do not assume a surgical abdomen has been ruled out simply because MIS-C is already suspected — both can coexist or mimic one another.[3]
- Inadequate response to first-line IVIG plus corticosteroid — see Treatment Failure/Next Step for urgent, specialist-directed escalation rather than a wait-and-see approach.[5]
The pharmacist's role here mirrors Kawasaki disease — recognition and prompt escalation, not outpatient reassurance — but with an even lower threshold given MIS-C's higher acuity.
Assessment & Diagnosis
Diagnosis rests on clinical, laboratory, and epidemiologic criteria together
See Recognize the Condition for the complete WHO and CDC/CSTE case-definition criteria. No single test is diagnostic; the diagnosis requires the fever/severity/inflammation criteria, at least 2 of the 5 organ-system categories, and SARS-CoV-2 laboratory or epidemiologic-linkage evidence, together with exclusion of a more likely alternative diagnosis.[2]
Laboratory findings
Beyond the CRP ≥3.0 mg/dL (30 mg/L) case-definition threshold, MIS-C typically shows markedly elevated ferritin, elevated D-dimer and other markers of coagulopathy, and — in a pattern that is a genuinely useful bedside distinguisher from Kawasaki disease — lymphopenia and thrombocytopenia rather than Kawasaki disease's characteristic subacute-phase thrombocytosis.[3][2] Mean ferritin has been reported around 610 ng/mL in MIS-C versus roughly 200 ng/mL in Kawasaki disease; mean lymphocyte counts around 800/µL in MIS-C versus roughly 2,800/µL in Kawasaki disease; and platelet counts around 151,000/µL (thrombocytopenic) in MIS-C versus a Kawasaki disease pattern of thrombocytosis exceeding 450,000/µL in the subacute phase.[3]
Cardiac evaluation
Obtain baseline echocardiography, ECG, troponin, and BNP/NT-proBNP in every patient at diagnosis, without delaying IVIG/corticosteroid treatment to do so.[6][1] Troponin and BNP/NT-proBNP elevations are typically far more pronounced in MIS-C than in Kawasaki disease, reflecting genuine myocardial involvement rather than coronary vasculitis alone — mean troponin around 45 ng/L (range 8-294) in MIS-C versus minimal elevation in Kawasaki disease, and mean BNP around 788 pg/mL in MIS-C versus roughly 41 pg/mL in Kawasaki disease.[3] Coronary artery involvement can still occur in MIS-C (reported in roughly 16.5% of cases) but is generally less frequent and less severe than in untreated Kawasaki disease.[3]
The central differential: MIS-C versus Kawasaki disease
These two conditions are related but genuinely distinct, and the CDC/CSTE case definition explicitly excludes a documented final diagnosis of Kawasaki disease from MIS-C classification.[2] The table below summarizes the key distinguishing features; use it together with the SARS-CoV-2 evidence/exposure requirement, which Kawasaki disease does not share.
| Feature | Kawasaki disease | MIS-C |
|---|---|---|
| Typical age | Mean roughly 3 years; ~76% under age 5 | Median roughly 7-9 years; range infancy to 20 years |
| SARS-CoV-2 link | Not required or expected | Required — current/recent infection or exposure within roughly 6 weeks (up to 60 days for laboratory evidence) |
| GI symptoms | Comparatively uncommon | Present in roughly 80% of cases — often a dominant feature |
| Shock/hypotension | Uncommon (Kawasaki disease shock syndrome affects a small minority) | Common — most patients develop some degree of hypoperfusion or shock |
| Myocardial/ventricular dysfunction | Uncommon | Substantially more common, reflecting genuine myocarditis-pattern involvement |
| Coronary artery involvement | 15-25% untreated, ~5% with timely IVIG | Reported in roughly 16.5% of cases — present, but generally less frequent/severe than untreated Kawasaki disease |
| Platelet count | Thrombocytosis, especially in the subacute phase | Thrombocytopenia is typical |
| Lymphocyte count | Typically normal/near-normal | Lymphopenia is typical |
| Ferritin, troponin, BNP | Minimal-to-modest elevation | Markedly higher, reflecting more pronounced systemic hyperinflammation and myocardial involvement |
[3] For the full Kawasaki disease diagnostic criteria, principal clinical features, and acute-phase management, see this platform's separate Kawasaki Disease chapter — it is deliberately not duplicated here.
Other differential diagnoses to exclude
Bacterial sepsis and toxic shock syndrome (staphylococcal/streptococcal), acute appendicitis or another surgical abdomen (given how prominent GI symptoms are in MIS-C), macrophage activation syndrome/secondary hemophagocytic lymphohistiocytosis from a cause other than MIS-C, acute COVID-19 pneumonia/myocarditis, and — in the adolescent age range — COVID-19-vaccine-associated myocarditis, which can present with some overlapping features but lacks MIS-C's multisystem/inflammatory-marker pattern and generally follows vaccination rather than infection.[2][3]
Treatment Targets
- Control systemic hyperinflammation early and effectively — the combination approach (IVIG plus upfront corticosteroid) exists specifically to reduce treatment failure compared with IVIG alone.[4]
- Recognize and treat shock or hemodynamic instability early — genuinely more common in MIS-C than in classic Kawasaki disease, and the complication most likely to drive ICU admission and short-term morbidity.[3]
- Provide antithrombotic prophylaxis for essentially every patient given MIS-C's hypercoagulable state, and escalate to therapeutic anticoagulation in the subset at highest thrombosis risk.[6][5]
- Reduce the risk and severity of coronary artery involvement, applying the same underlying principle as Kawasaki disease even though the absolute risk and pattern differ.[3]
- Identify treatment failure early and escalate appropriately — favouring corticosteroid intensification or a biologic over reflexively repeating IVIG, given the volume-overload/hemolytic-anemia risk of a second large infusion in a population prone to myocardial dysfunction.[5]
- Assess cardiac function and fluid status before the first IVIG infusion, not only after a complication develops.[5]
- Support the family through a genuinely frightening, often ICU-level acute illness, including honest counselling that some aspects of MIS-C's long-term outcome data are still accumulating since it is a comparatively new condition.
Choose Initial Treatment
IVIG plus upfront corticosteroid — the preferred combination, not IVIG alone
Every confirmed or probable case: before treating, assess cardiac function and fluid status (echocardiogram, ECG, troponin, BNP/NT-proBNP already obtained per Assessment & Diagnosis).[5] Give IVIG 2 g/kg IV (based on ideal body weight, maximum 100 g) as a single infusion — or, specifically if significant cardiac dysfunction or fluid sensitivity is present, divided as 1 g/kg/day over 2 days — together with a low-to-moderate dose corticosteroid started at the same time (oral or IV, roughly 1-2 mg/kg/day).[6][5] This upfront combination reduced treatment failure from 38% (IVIG alone) to 9% in a propensity-matched cohort, and was also associated with less need for second-line therapy, less hemodynamic support, less post-treatment left ventricular dysfunction, and a shorter PICU stay — a genuinely important, relatively recent shift from earlier practice that used IVIG alone and reserved corticosteroids for treatment failure.[4]
Shock, significant myocardial dysfunction, or a need for high-dose or multiple inotropes/vasopressors: use high-dose IV pulse methylprednisolone (10-30 mg/kg/day, maximum 1000 mg/dose) in place of the low-to-moderate dose, alongside IVIG, careful/judicious fluid resuscitation, inotropic or vasopressor support, and ICU admission.[6][5]
Antithrombotic therapy — low-dose aspirin for essentially everyone
Start low-dose aspirin (3-5 mg/kg/day PO, maximum 81 mg/day) in essentially every MIS-C patient for antithrombotic prophylaxis, reflecting the hypercoagulable state of MIS-C, and continue until the platelet count has normalized and a follow-up echocardiogram beyond 4 weeks confirms normal coronary arteries.[6]
A different rationale for aspirin than in Kawasaki disease. MIS-C's aspirin regimen is a single, low, antithrombotic dose from the outset, reflecting a thrombosis-prevention rationale — unlike classic Kawasaki disease, which uses a higher anti-inflammatory dose during the febrile phase before transitioning to a low antiplatelet dose (see the Kawasaki Disease chapter). The deliberate exception to routine pediatric aspirin avoidance due to Reye syndrome applies equally here and should be explained proactively to concerned caregivers.[6]
Escalating antithrombotic therapy for higher thrombosis risk
For patients with a giant coronary aneurysm (Z-score ≥10), an ejection fraction under 35%, or a documented thrombus, escalate from aspirin alone to therapeutic anticoagulation (e.g. enoxaparin), specialist-directed.[5]
Biologic escalation for refractory disease — and why a second IVIG dose is not the default
For inadequate response to IVIG plus corticosteroid, escalate to a biologic — anakinra is generally preferred, particularly with macrophage-activation-syndrome features, while infliximab is a reasonable alternative, particularly for a more Kawasaki-like or GI-predominant refractory phenotype; the choice between the two is specialist-directed.[5] Do not reflexively repeat a full second dose of IVIG in refractory MIS-C the way a second IVIG dose is sometimes used in refractory Kawasaki disease — the large infused volume (roughly 40 mL/kg) carries a genuine risk of volume overload and hemolytic anemia, a risk that is amplified in MIS-C's much higher background rate of myocardial dysfunction. See Treatment Failure/Next Step for the full escalation pathway.[5]
Non-Pharmacologic Treatment
- Admit every patient with confirmed or probable MIS-C — given the substantially higher shock rate than Kawasaki disease, have a low threshold for ICU-level admission from the outset rather than only after deterioration.[3]
- Assess cardiac function and fluid status before the first IVIG infusion in every patient, not only those who already look unwell — this specifically shapes whether a single 2 g/kg infusion or a divided 1 g/kg/day-over-2-days regimen is safer.[5]
- For shock or significant hemodynamic instability: careful, judicious fluid resuscitation (rather than the more liberal boluses used in typical pediatric septic shock, given the higher prevalence of myocardial dysfunction), inotropic or vasopressor support as needed, and possible intubation/mechanical ventilation, managed in an ICU setting.[6]
- Involve pediatric cardiology, critical care, and rheumatology or infectious diseases early and continuously — MIS-C management is genuinely multidisciplinary from the point of diagnosis, more so than typical Kawasaki disease.[6]
- Anticipate and monitor for fluid overload after large-volume IVIG in a patient with depressed ejection fraction; be prepared to add diuresis once the patient is hemodynamically stabilized (see Pharmacologic Treatment Options).
- Confirm the aspirin dose and its specific stop criterion (normalized platelets plus a ≥4-week echocardiogram confirming normal coronaries) are documented and communicated before discharge.[6]
- Arrange the full serial echocardiography follow-up schedule and a first outpatient cardiology visit starting 2-3 weeks after discharge before the patient leaves hospital — do not leave this to be arranged later.[6][1]
- Provide clear caregiver education: the deliberate, guideline-endorsed reason for using aspirin despite the usual Reye syndrome caution; the genuine value of ongoing COVID-19 vaccination in reducing the risk of a future MIS-C episode; and, for any child found to have coronary or ventricular abnormalities, honest counselling about the follow-up and antithrombotic therapy that will be needed.[6][1]
- Arrange psychological support for families navigating a frightening acute illness, often involving an ICU stay, and — where relevant — an ongoing cardiac diagnosis.
Special Populations
Shock and ICU-level MIS-C — the most important special population in this chapter
Most MIS-C patients develop some degree of hypoperfusion or shock, versus a small minority (Kawasaki disease shock syndrome) in classic Kawasaki disease.[3] This group needs early critical-care involvement, high-dose IV pulse corticosteroid rather than the low-to-moderate dose, careful/judicious fluid resuscitation given the higher prevalence of myocardial dysfunction, and inotropic/vasopressor support.[6][5]
Significant myocardial/ventricular dysfunction
Assess cardiac function and fluid status before the first IVIG infusion in every patient; consider the divided 1 g/kg/day-over-2-days IVIG regimen specifically in this group, monitor closely for volume overload after infusion, and be prepared to add diuresis once stabilized.[5] The large majority of patients with MIS-C-associated ventricular dysfunction show meaningful improvement in ejection fraction within days to a few weeks of treatment, which is genuinely reassuring information to share with anxious families once the acute phase has stabilized.[3][5]
Infants and very young children
MIS-C is less common in this age group than in the school-age/adolescent range where it predominates, and distinguishing it from classic Kawasaki disease can be especially difficult at younger ages; apply the CDC/CSTE exclusion criterion carefully (a documented Kawasaki disease diagnosis excludes MIS-C classification) and involve pediatric specialists early.[2]
Adolescents
Adolescents fall within the CDC/CSTE case definition's under-21 age range and are old enough that COVID-19-vaccine-associated myocarditis becomes a relevant differential/coincident consideration; distinguish based on the multisystem/inflammatory-marker pattern and the fever/organ-involvement criteria that vaccine-associated myocarditis does not share (see Assessment & Diagnosis).[2]
IgA deficiency
As with any IVIG indication, anaphylaxis is a recognized risk in patients with known IgA deficiency; screen where feasible and have the treating team plan accordingly.
Future COVID-19 vaccination after MIS-C
COVID-19 vaccination genuinely reduces the risk of a subsequent MIS-C episode, and current public health guidance supports vaccination after clinical recovery from MIS-C, including a return to baseline cardiac function; specific timing should follow current public health and specialist guidance rather than being initiated independently.[1]
Renal and hepatic considerations
Use IVIG cautiously in renal impairment, favouring a non-sucrose formulation and adequate hydration where feasible. Aspirin should be used with attention to bleeding risk and GI tolerability in any child with a bleeding diathesis or significant hepatic impairment; there is no MIS-C-specific dose adjustment beyond standard pediatric practice.
Monitoring & Follow-Up
Echocardiography and cardiac follow-up schedule
Obtain baseline echocardiogram, ECG, troponin, and BNP/NT-proBNP at diagnosis, without delaying IVIG/corticosteroid treatment. Repeat echocardiography at 7-14 days and again at 4-6 weeks after diagnosis — a schedule that parallels, but is not identical to, classic Kawasaki disease's 2-week/4-6-week convention.[6] Arrange the first outpatient pediatric cardiology follow-up visit starting 2-3 weeks after discharge for every patient.[1]
Long-term management, stratified by cardiac findings
- No coronary involvement and normalized ejection fraction confirmed on follow-up echocardiography: discontinue low-dose aspirin once the platelet count has normalized and the ≥4-week echocardiogram confirms normal coronary arteries.[6]
- Coronary dilation or a small-to-medium aneurysm: continue low-dose aspirin long-term with periodic cardiology follow-up, using the same coronary-artery Z-score risk-stratification framework described in this platform's Kawasaki Disease chapter.[3]
- Large/giant aneurysm, ejection fraction under 35%, or a documented thrombus: add therapeutic anticoagulation to antiplatelet therapy, with long-term specialized cardiology follow-up.[5]
Ventricular function recovery
The large majority of patients with MIS-C-associated ventricular dysfunction show meaningful improvement in ejection fraction within days to a few weeks — genuinely reassuring information once the acute phase has stabilized, though re-check function at each follow-up rather than assuming recovery without confirming it.[3][5]
Complications and honest evidence limitations
Coronary artery involvement, persistent ventricular dysfunction, and arrhythmia are the central cardiac complications to track. Because MIS-C is a comparatively recently described condition, long-term (multi-year) outcome data are still accumulating — be honest with families that some aspects of very-long-term prognosis remain under active study, even as short- and medium-term outcomes with prompt treatment are generally favourable.[3]
Common Errors to Avoid
- Treating MIS-C as "just Kawasaki disease with a positive COVID test" — using Kawasaki disease's higher, anti-inflammatory acute aspirin dose rather than MIS-C's low, antithrombotic dosing, or skipping the SARS-CoV-2 evidence/exposure requirement that genuinely distinguishes the two conditions.[6][2]
- Reflexively repeating a full second dose of IVIG in refractory MIS-C without considering the volume-overload/hemolytic-anemia risk, particularly in the depressed-ejection-fraction patient this disease disproportionately produces — favour corticosteroid intensification or a biologic instead.[5]
- Underestimating shock risk, or not involving critical care early enough, given MIS-C's markedly higher shock rate than classic Kawasaki disease.[3]
- Delaying IVIG/corticosteroid treatment while awaiting definitive SARS-CoV-2 laboratory confirmation in a clinically convincing, probable case — epidemiologic linkage alone is sufficient for a probable case, and treatment should not wait on confirmatory testing.[2]
- Missing an alternative diagnosis — bacterial sepsis/toxic shock syndrome, a surgical abdomen given how prominent GI symptoms are in MIS-C, or a documented Kawasaki disease, which should specifically be excluded from MIS-C classification rather than treated as the same illness.[2]
- Failing to arrange the full serial echocardiography schedule (7-14 days, 4-6 weeks) and the first outpatient cardiology visit at 2-3 weeks before discharge.[6][1]
- Assuming a normal baseline echocardiogram rules out later coronary or ventricular involvement — MIS-C, like Kawasaki disease, can still evolve after the initial study, which is precisely why the serial schedule exists.[6]
- Withholding aspirin out of a general Reye-syndrome-related reflex against pediatric aspirin use — this is a specific, deliberate, guideline-endorsed exception, not an oversight, and should be explained proactively.[6]
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
Disease-Modifying Acute Therapy — First-Line Combination
Give the corticosteroid together with IVIG from the outset for every confirmed or probable case — this upfront combination, not IVIG alone, is the current evidence-preferred approach.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Immunoglobulin (Human) — IVIG | Standard dose: 2 g/kg IV (ideal body weight, maximum 100 g), single infusion Divided dose (cardiac dysfunction/fluid-sensitive): 1 g/kg/day IV for 2 consecutive days | Aseptic meningitis, hemolytic anemia (risk rises with repeat/large cumulative doses), anaphylaxis in IgA-deficient patients, volume overload with depressed ejection fraction | May reduce the efficacy of live vaccines given within about 11 months of infusion | Assess cardiac function/fluid status first; consider the divided regimen for significant cardiac dysfunction; do not reflexively repeat a full dose if refractory. |
| Prednisone / prednisolone — low-to-moderate dose | Standard dose: 1-2 mg/kg/day PO or IV | Hyperglycemia, mood changes, GI upset, immunosuppression | Additive hyperglycemia with other agents affecting glucose control | Start together with IVIG in essentially every patient; reduces treatment failure versus IVIG alone (9% vs 38%). |
| Methylprednisolone sodium succinate — high-dose IV pulse | Pulse dose: 10-30 mg/kg/day IV, maximum 1000 mg/dose | Hyperglycemia, hypertension, GI bleeding, adrenal suppression with repeated dosing | Additive hyperglycemia with other agents affecting glucose control | Reserved for shock, significant myocardial dysfunction, or a need for high-dose/multiple inotropes or vasopressors — used in place of, not added to, the low-to-moderate dose. |
Antiplatelet and Anticoagulant Therapy
Aspirin's role here is antithrombotic prophylaxis for the hypercoagulable state of MIS-C — a different rationale from Kawasaki disease's higher acute anti-inflammatory dosing, even though it is the same drug and the Reye-syndrome exception applies equally.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Acetylsalicylic acid (ASA) — low, antithrombotic dose | Standard dose: 3-5 mg/kg/day PO, maximum 81 mg/day | GI upset, bleeding risk | Additive bleeding risk with other antiplatelet agents or anticoagulants | Continue until platelet count normalizes and a follow-up echocardiogram beyond 4 weeks confirms normal coronary arteries. |
| Enoxaparin | Dose: Specialist-directed, weight-based | Bleeding, injection-site bruising, rare heparin-induced thrombocytopenia | Additive bleeding risk with antiplatelet agents or other anticoagulants | Reserved for higher-thrombosis-risk patients — giant aneurysm (Z-score ≥ 10), ejection fraction under 35%, or a documented thrombus — added to or in place of low-dose aspirin. |
Second-Line Biologic Therapy for Refractory Disease
For inadequate response to IVIG plus corticosteroid. A full second IVIG dose is deliberately not the default escalation in MIS-C, given the volume-overload/hemolytic-anemia risk in a population already prone to myocardial dysfunction — escalate to one of these instead, specialist-directed.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Anakinra | Dose: Specialist-directed, weight-based, subcutaneous or IV | Injection-site reactions, infection risk, neutropenia | Additive infection risk with other immunosuppressants | Generally preferred, particularly with macrophage-activation-syndrome features. |
| Infliximab | Standard dose: 5 mg/kg IV single infusion, specialist-directed | Infusion reactions, infection risk, rare hepatotoxicity | Avoid with live vaccines; additive infection risk with other immunosuppressants | A reasonable alternative, particularly for a more Kawasaki-like or GI-predominant refractory phenotype. |
Hemodynamic and Shock Support — ICU-Directed
Reflects MIS-C's substantially higher shock rate than classic Kawasaki disease. Included for pharmacist awareness of the full inpatient/ICU care pathway; dosing and agent selection are critical-care/specialist-directed.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Epinephrine | Dose: ICU/specialist-directed continuous infusion | Tachyarrhythmia, hypertension, peripheral/digital ischemia with extravasation | Additive arrhythmia risk with other sympathomimetics or QT-prolonging agents | A first-line vasopressor/inotrope option for MIS-C-associated shock; choice among agents follows the dominant hemodynamic pattern. |
| Norepinephrine | Dose: ICU/specialist-directed continuous infusion | Peripheral/digital ischemia with extravasation, arrhythmia | Additive arrhythmia risk with other sympathomimetics or QT-prolonging agents | Alternative first-line vasopressor, particularly with a more vasodilatory shock pattern. |
| Milrinone | Dose: ICU/specialist-directed continuous infusion | Hypotension, arrhythmia | Additive hypotension with other vasodilators or antihypertensives | Considered when depressed ejection fraction/myocardial dysfunction, rather than vasodilatory physiology alone, is the dominant driver of shock. |
| Furosemide | Dose: Specialist-directed | Electrolyte disturbances, hypotension with aggressive dosing, ototoxicity at high IV doses | Additive ototoxicity with other ototoxic drugs; additive hypotension with antihypertensives | For diuresis once hemodynamically stabilized, particularly after large-volume IVIG in a patient with depressed ejection fraction. |
References
- Information for Healthcare Providers about Multisystem Inflammatory Syndrome in Children (MIS-C) — Centers for Disease Control and Prevention. CDC, archived version, reviewed 2023 Jan 3
- Council of State and Territorial Epidemiologists/CDC Surveillance Case Definition for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection — United States — MMWR Recommendations and Reports, Centers for Disease Control and Prevention. MMWR Recomm Rep 2022;71(4):1-14, effective 2023 Jan 1
- Kawasaki Disease and Multisystem Inflammatory Syndrome in Children: An Overview and Comparison — American Family Physician (Darby JB, Jackson JM). Am Fam Physician 2021;104(3):244-252
- Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children — JAMA (Ouldali N, Toubiana J, Antona D, et al; French Covid-19 Paediatric Inflammation Consortium). JAMA 2021;325(9):855-864
- American College of Rheumatology Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19: Version 3 — Arthritis & Rheumatology, American College of Rheumatology (Henderson LA, Canna SW, Friedman KG, et al.). Arthritis Rheumatol 2022;74:e1-e20, published 2022 Feb 3
- Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (spring 2021 update) — Canadian Paediatric Society, Acute Care Committee (Berard RA, Tam H, Scuccimarri R, Haddad E, Morin MP, Chan KJ, Dahdah NS, McCrindle BW, Price VE, Yeung RSM, Laxer RM). Canadian Paediatric Society Position Statement, posted 2020 Jul 6, updated 2021 May 3
- Multisystem inflammatory syndrome in children and adolescents with COVID-19 — World Health Organization. WHO Scientific Brief, WHO/2019-nCoV/Sci_Brief/Multisystem_Syndrome_Children/2020.1, published 2020 May 15
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.