Development of a Model to Identify Febrile Children at Low Risk for Multisystem Inflammatory Syndrome

Abstract

Objectives The case definition for multisystem inflammatory syndrome in children (MIS-C) is broad and encompasses symptoms and signs commonly seen in children with fever. Our aim was to identify clinical predictors that, independently or in combination, identify febrile children presenting to the emergency department (ED) as low risk for MIS-C. Methods We conducted a retrospective single-center study of otherwise healthy children 2 months to 20 years of age presenting to the ED with fever and who had a laboratory evaluation for MIS-C between April 15, 2020, and October 31, 2020. We excluded children with a diagnosis of Kawasaki disease. Our outcome was an MIS-C diagnosis defined by the Centers for Disease Control and Prevention criteria. We conducted multivariable logistic regression analyses to identify variables independently associated with MIS-C. Results Thirty-three patients with and 128 patients without MIS-C were analyzed. Of those with MIS-C, 16 of 33 (48.5%) had hypotension for age, signs of hypoperfusion, or required ionotropic support. Four variables were independently associated with the presence of MIS-C; known or suspected SARS CoV-2 exposure (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4–11.9) and the following 3 symptoms and signs: abdominal pain on history (aOR, 4.8; 95% CI, 1.7–15.0), conjunctival injection (aOR, 15.2; 95% CI, 5.4–48.1), and rash involving the palms or soles (aOR, 12.2; 95% CI, 2.4–69.4). Children were at low risk of MIS-C if none of the 3 symptoms or signs were present (sensitivity 87.9% [95% CI, 71.8–96.6]; specificity 62.5% [53.5–70.9], negative predictive value 95.2% [88.3–98.7]). Of the 4 MIS-C patients without any of these 3 factors, 2 were ill-appearing in the ED and the other 2 had no cardiovascular involvement during their clinical course. Conclusions A combination of 3 clinical symptoms and signs had moderate to high sensitivity and high negative predictive value for identifying febrile children at low risk of MIS-C. If validated, these factors could aid clinicians in determining the need to obtain or forego an MIS-C laboratory evaluation during SARS-CoV-2 prevalent periods in febrile children.