Four weeks after a COVID exposure, children may not be completely in the clear. MIS-C is a post-infectious inflammatory state that affects pediatric patients and can lead to heart failure, acute abdomen, and a new Kawasaki-like syndrome in older ages. We discuss the emerging evidence with expert, Dr. Adriana Tremoulet ( UCSD), who sits on the American College of Rheumatology MIS-C and COVID-19 Related Hyperinflammation Task Force. She educates us on the presentation, diagnosis, and management MIS-C so when you see this condition, you’ll be ready!
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Typically, a child with MIS-C will have had fevers for days and will be ill-appearing. There are a few questions that the examiner can ask to investigate MIS-C on the differential diagnosis:
If the answer is no to all of these questions, it is less likely to be MIS-C.
There appear to be at least three main presentations of MIS-C:
Producer’s Note: Most common clinical presentations include [UpToDate 2020]:
If your suspicion for MIS-C is high, initial workup may include:
Dr. Tremoulet’s advice: If you decide to obtain labs, though, be sure that you have a plan to act upon them (whether it is more frequent follow-up versus asking them to present to the Emergency Department for potential admission).
The Centers for Disease Control and Prevention (2020) defines MIS-C as:
1. An individual < 21yo with fever and laboratory evidence of inflammation (one or more of the following: elevated CRP, ESR< fibrinogen, procalcitonin, D-dimer, ferritin, LDH, or IL-6; elevated neutrophils; reduced lymphocytes; and low albumin),
2. Clinically significant illness requiring hospitalization with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurologic).
3. No alternative plausible diagnoses
4. Positive for current or recent SARS-CoV-2 infection OR COVID-19 exposure within the 4 weeks prior to onset of symptoms.
Producer’s Note: The World Health Organization definition of MIS-C (2020) differs from that of the CDC primarily in the first criterion:
Children and adolescents 0-19y of age with fever < 3d AND 2 of the following:
Diagnosis requires an interdisciplinary team of consults, oftentimes including infectious disease, rheumatology, and cardiology. This differential diagnosis includes toxic shock syndrome, Kawasaki disease, vasculitis, viral cardiomyopathy, etc.
Ideally, there should be an institution work-up designed to aid in workflow, but further labwork that you may want to obtain to check a baseline and/or trend include:
Dr. Tremoulet Expert Pearl: If your platelet count is low and you have a consumptive coagulopathy, the body may not be able to mount an elevated ESR so it may appear low, but don’t be thrown off and think there is no inflammation.
Differences between MIS-C and KD: MIS-C can have more effect on heart function (with an associated elevation in BNP), while KD has more effect on coronary arteries. Presentations differ a bit too. Patients with MIS-C will often have diarrhea and GI complaints, which we don’t frequently see in KD. Often, inflammatory markers in KD, while elevated, will not be as high as those seen in patients presenting with MIS-C.
Presentation of MIS-C in adults has been documented.
These patients can present in cardiogenic shock due to poor cardiac output. Thus, medical teams should be cautious with fluid resuscitation because over resuscitation could result in rapidly deteriorating respiratory function due to pulmonary edema.
In a study of 58 patients with MIS-C, 29 children (50%) developed shock and required inotropic support (Whittaker 2020). Concern for cardiac involvement is suggested by tachycardia (while afebrile) and an elevated BNP, though the diagnosis of heart failure is clinical.
For work-up, complete echo is required (function, coronary arteries, and coronary Z-scores). The EKG is important to evaluate for potential arrhythmias that have been documented in this patient population (Samuel 2020; Whittaker 2020).
If there are abnormalities on the EKG, it is recommended to repeat it every 48 hours to ensure there are no worsening findings (Henderson 2020). Similarly, abnormal Echos should be followed closely (7 days after discharge and more frequently inpatient as needed).
If the patient is admitted to the floor and is stable, there is time for consultants to evaluate and make recommendations for the patient’s care to rule out other potential etiologies. The consultants will typically be a combination of infectious diseases, rheumatology, and cardiology.
Once other diagnoses have been ruled out, the initial treatment is dependent on the patient’s course. If the patient has clinically improved and defervesced, there may not be any additional interventions necessary. Based on an interdisciplinary approach, clinical progression (e.g., persistence of fevers, worsening vitals), and severity of organ involvement (e.g., cardiogenic shock, coronary artery aneurysms), the initiation of treatment is subjective at times, but the typical first-line therapies are steroids versus IVIG. (This is extrapolated partially out of the data surrounding Kawasaki disease, and there are no randomized controlled trials that support first-line therapy in MIS-C at this time.)
Where the management becomes more complex is what happens if the fever recrudesces after the initial treatment. In Kawasaki disease, this is believed to be a treatment failure. The clinical variation in second-line agents is quite drastic and depends on your consultants. Possible agents include anakinra, infliximab, tocilizumab, and a second-round of IVIG.
Dr. Tremoulet’s expert opinion: Think carefully prior to administering a second-round of IVIG since it is a large volume load (in patients who may have borderline cardiac function) and it increases the risk of hemolytic anemia.
It is unclear whether these treatments will reduce the incidence of coronary artery aneurysms (like IVIG has been shown to do in Kawasaki Disease).
The major complication to monitor for is the development of cardiogenic shock. These patients can quickly go from compensated (perfusing well with sufficient cardiac output) to shock (where their cardiac function can no longer support their metabolic needs) that may require transfer to the Intensive Care Unit. Additionally, patients can develop worsening colitis that may even require surgical management.
Overall, these patients do extremely well and normally recover. Unfortunately, at this time, we do not know the natural history of this disease and if/what the long-term consequences of it will be.
For a safe discharge, it is recommended:
Dr. Tremoulet recommendation: Make a follow-up as easy as possible. The ideal follow-up would consist of multiple providers seeing the patient in a fashion that is convenient for them if possible. Additionally, make sure there is one subspecialist as the point of contact once the patient is discharged to ensure they are not lost to follow-up and can get any questions answered.
Listeners will explain the basic clinical manifestations, diagnosis, and management of MIS-C to improve both inpatient emergent care and outpatient follow-up.
After listening to this episode listeners will…
Dr. Tremoulet reports no relevant financial disclosures. The Cribsiders report no relevant financial disclosures.
Tremoulet A, Lee N, Chui C, Berk J. “#5 What’s in a Name? MIS-C”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ August 12, 2020.
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