Multisystem inflammatory syndrome in children (MIS-C) and sepsis differentiation by a clinical and analytical score: MISSEP score

Abstract

Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex. The aims were to evaluate the differences between pediatric patients with MIS-C and sepsis and to develop a score to distinguish both entities. This was a retrospective study that compared demographic, clinical, diagnostic, and therapeutic data of pediatric patients with MIS-C (cohort 2020–2022) and sepsis (cohorts 2010–2014 and 2017–2018) admitted to a Pediatric Intensive Care Unit (PICU) of a tertiary care hospital. A diagnostic score was developed with variables that differentiated the two conditions. Twenty-nine patients with MIS-C were identified, who were matched 1:3 with patients with sepsis (n = 87). Patients with MIS-C were older (10 vs. 4 years old), and the majority were male (69%). Clinical characteristics that demonstrated differences were prolonged fever and signs and symptoms affecting skin-mucosa and gastrointestinal system. Leukocytes, PCT, and ferritin were higher in sepsis, while thrombocytopenia, lymphopenia, and elevated fibrinogen and adrenomedullin (biomarker with a role for the detection of invasive infections) were more frequent in MIS-C. MIS-C patients presented greater myocardial dysfunction (p < 0.001). Five criteria were selected and included in the MISSEP score after fitting them into a multivariate logistic regression model: fever > 48 hours (20 points), thrombocytopenia < 150 × 103/µL (6 points), abdominal pain (15 points), conjunctival erythema (11 points), and Vasoactive Inotropic Score (VIS) > 10 (7 points). The cutoff > 25 points allowed to discriminate MIS-C from sepsis with a sensitivity of 0.89 and specificity of 0.95. Conclusion: MIS-C phenotype overlaps with sepsis. MISSEP score could be useful to distinguish between both entities and direct specific treatment. What is Known:• Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex.• It is essential to establish an accurate initial diagnosis and early specific treatment in both cases of MIS-C and sepsis to improve the prognosis of these patients. What is New:• Patients with MIS-C are older and have characteristic symptoms of prolonged fever, gastrointestinal symptoms, skin-mucosal involvement, and greater myocardial dysfunction, compared to patients with sepsis.• The use of diagnostic scores, such as the MISSEP score, can be very useful to distinguish between the two entities and help direct specific treatment.