MIS-C, or multisystem inflammatory syndrome in children, is an uncommon syndrome of severe inflammation that occurs in some children and adolescents 2-6 weeks after exposure to COVID-19, the disease caused by the severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2. MIS-C can affect multiple organs including the gut, brain, eyes, skin, heart, and lungs. Children present with persistent fevers, GI symptoms such as abdominal pain, vomiting and diarrhea, rash, conjunctivitis, red or swollen lips or tongue, irritability or headache, listlessness, and trouble breathing. Black and Latino children are disproportionally affected. MIS-C resembles other inflammatory disorders such as macrophage activation syndrome (MAS), Kawasaki Disease (KD), and cytokine storm syndrome.
What Causes MIS-C?
MIS-C is caused by an abnormal immune system’s response to COVID-19 exposure. After exposure to COVID-19, the immune system of some children produces an exaggerated immune response with large amounts of immunoglobulins and inflammatory substances called cytokines. This abnormal inflammatory response results in the features of the disease and may cause injury to various organs.
How Is MIS-C Diagnosed?
There is no one specific test to diagnose MIS-C; the diagnosis is made based on a child’s symptoms, including the presence of fever, evidence of involvement of several organ systems, evidence of prior COVID-19 infection, and exclusion of other causes. Pediatric rheumatologists and treating physicians may obtain several laboratory and diagnostic tests to support the diagnosis of MIS-C. Laboratory tests may include SARS-CoV-2 PCR to test for active COVID-19 infection, SARS-CoV 2 IgG/serologies to test for past COVID-19 infection, complete blood counts (CBC), inflammatory markers (e.g., CRP, ESR, ferritin), markers of heart injury (i.e., troponin and BNP), and coagulation factors (e.g., D-dimer, PT, PTT, INR). Imaging studies that may be obtained are chest x-rays, echocardiograms (ECHO), electrocardiograms (EKG’s), and chest CT’s (i.e., computed tomography).
How Is MIS-C Treated?
Most children with MIS-C are treated in the hospital. As patients may present in shock, fluids and antibiotics are often administered until an active infection can be ruled out. Most patients with MIS-C are treated with immunomodulatory agents including steroids and IVIG (intravenous immunoglobulin) to dampen the immune system response. For patients who do not improve, addition of infliximab (a tumor necrosis factor [TNF] inhibitor), or anakinra (an interleukin-1 [IL-1]) inhibitor) can be added. Due to the increased risk for clots in patients with MIS-C, patients are also treated with low-dose aspirin. The child’s symptoms and the severity of illness will determine which treatments are needed.
The best way to prevent MIS-C is to prevent infection from COVID-19. Frequent hand washing, social distancing, wearing a mask, and obtaining the COVID-19 vaccination series with booster, have all been shown to decrease the risk of contracting COVID-19.
Living with MIS-C
With prompt diagnosis and proper treatment, most children will make a full recovery from MIS-C. At discharge, patients with MIS-C are closely monitored on an outpatient basis by pediatric specialists in rheumatology, infectious disease, and hematology. In cases where there is heart involvement, particularly close follow-up with a pediatric cardiologist is required.
The Rheumatologist's Role in the Treatment of MIS-C
MIS-C is a multi-system, multi-organ illness that requires the expertise of multiple specialists. This includes infectious disease doctors, critical care doctors, hematologists, and cardiologists. Pediatric rheumatologists assist in the diagnosis of MIS-C and may aid in the dosing and administration of immunomodulatory medications.
Written July 2022 by Nina T. Washington, MD, MPH and reviewed by Jonathan Hausmann, MD.
This information is provided for general education only. Individuals should consult a qualified health care provider for professional medical advice, diagnosis and treatment of a medical or health condition.