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Some children may be at risk for multiple episodes of multisystem inflammatory syndrome in children (MIS-C), according to from physicians at Le Bonheur Children’s Hospital and the University of Tennessee Health Science Center (UTHSC). The article describes the case of one child with two distinct illnesses seven months apart that were both consistent with MIS-C. The report highlights the need for more guidance and better understanding of the syndrome in order to improve diagnosis and treatment of these patients.

The article was published by a group of Le Bonheur and UTHSC physicians — former Pediatric Hospital Medicine Fellow W. Caleb Hancock, MD, Infectious Disease Fellow Amanda M. Green, MD, Child Neurology Resident Sariha Moyen, MD, Pediatrics Resident Caitlin Creel, MD, Rheumatologist Kathleen P. Collins, MD, Vice Chair of Clinical Affairs and Rheumatologist Terri Finkel, MD, PhD, Hospitalist Stephen D. Pishko, MD, and Infectious Disease Specialist and UTHSC Pediatrics Residency Program Director Bindiya Bagga, MD.

“Our patient exhibited two distinct illnesses, both of which met the clinical and laboratory case definitions of MIS-C and could not be unambiguously explained by another etiology,” said Bagga. “Our case introduces the possibility that a subset of children may be more likely to have repeat MIS-C.”

In June 2020, a child presented to Le Bonheur Children’s with primarily neurological and gastrointestinal symptoms as well as elevated inflammatory markers. A COVID-19 PCR test was negative, but the child had suspected exposure to COVID-19. When an extensive workup for alternative diagnoses was negative, a SARS-CoV-2 antibody test was positive and the viral respiratory panel was negative, physicians gave the diagnosis of MIS-C. The child improved after intravenous immune globulin (IVIG) treatment and spent 14 days inpatient. Three weeks after discharge in outpatient follow up, the child had fully recovered from all symptoms.

In January 2021 after seven months of good health, the child presented again — this time with fever, rash, gastrointestinal symptoms, elevated inflammatory markers and dilation of the left anterior descending coronary artery. The child had no known direct exposure to COVID-19. Symptoms, findings on electrocardiogram (EKG) and transthoracic echocardiogram (TTE) and abnormal laboratory results again led to a diagnosis of MIS-C. Treatment with high-dose aspirin, IVIG and methylprednisolone was initiated and by day five, all lab results except D-dimer were normal. At a follow up with cardiology two weeks after discharge, the coronary dilation had resolved.

“In the interim between illnesses, the patient returned to a usual state of good health and demonstrated resolution of laboratory abnormalities,” said Bagga. “This case is not consistent with prior reports that have described rebound MIS-C symptoms after completion of therapy — it is possible the separate illnesses were triggered by different variants of SARS-CoV-2.”

Le Bonheur physicians posit that some high risk variants of SARS-CoV-2 may be more likely to trigger MIS-C and that individuals with defects in inflammatory pathways may also be at increased risk.

“Further immunologic and virologic characterization of cases of MIS-C is warranted to improve our understanding of this entity, and we hope our case report increases awareness of the possibility that repeat MIS-C illness can occur in their patients,” said Bagga.