Differentiating multisystem inflammatory syndrome in children: a single-centre retrospective cohort study

Abstract

ObjectiveFeatures of multisystem inflammatory syndrome in children (MIS-C) overlap with other febrile illnesses, hindering prompt and accurate diagnosis. The objectives of this study were to identify clinical and laboratory findings that distinguished MIS-C from febrile illnesses in which MIS-C was considered but ultimately excluded, and to examine the diseases that most often mimicked MIS-C in a tertiary medical centre.Study designWe identified all children hospitalised with fever who were evaluated for MIS-C at our centre and compared clinical signs and symptoms, SARS-CoV-2 status and laboratory studies between those with and without MIS-C. Multivariable logistic LASSO (least absolute shrinkage and selection operator) regression was used to identify the most discriminative presenting features of MIS-C.ResultsWe identified 50 confirmed MIS-C cases (MIS-C+) and 68 children evaluated for, but ultimately not diagnosed with, MIS-C (MIS-C-). In univariable analysis, conjunctivitis, abdominal pain, fatigue, hypoxaemia, tachypnoea and hypotension at presentation were significantly more common among MIS-C+ patients. MIS-C+ and MIS-C- patients had similar elevations in C-reactive protein (CRP), but were differentiated by thrombocytopenia, lymphopenia, and elevated ferritin, neutrophil/lymphocyte ratio, BNP and troponin. In multivariable analysis, predictors of MIS-C included age, neutrophil/lymphocyte ratio, platelets, conjunctivitis, oral mucosa changes, abdominal pain and hypotension.ConclusionsAmong hospitalised children undergoing evaluation for MIS-C, children with MIS-C were older, more likely to present with conjunctivitis, oral mucosa changes, abdominal pain and hypotension, and had higher neutrophil/lymphocyte ratios and lower platelet counts. These data may be helpful for discrimination of MIS-C from other febrile illnesses, including bacterial lymphadenitis and acute viral infection, with overlapping features.

Epidemiological characterization of SARS-CoV-2 variants in children over the four COVID-19 waves and correlation with clinical presentation

“…Reports of hospitalization and severe long-term manifestations are less frequent than adults, but not negligible. Severe and multiple COVID-19 related illnesses were indeed reported in young people who test positive for SARS-CoV-2 by several independent groups [6][7][8][9]9,10 . Multisystem inflammatory syndrome (MIS-C), and myocarditis were the long-term COVID-19 related manifestations, mostly related with young age 8,9,9,10 .…”

American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 3

“…Neurologic involvement is also reported, manifesting as severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke in select patients (5)(6)(7)13,14,(19)(20)(21)(22)(23). These findings are nonspecific and can occur in other infections, as well as in non-infection-related conditions such as oncologic or inflammatory conditions (24). In the midst of the COVID-19 pandemic, there is potential for cognitive bias with anchoring on a diagnosis of MIS-C when children present with unexplained fevers.…”

SARS-CoV-2 Infection and Associated Cardiovascular Manifestations and Complications in Children and Young Adults: A Scientific Statement From the American Heart Association

“…As many as 50% of children with MIS-C have myocardial involvement, including decreased left ventricular function (defined as an ejection fraction <55%) in 28% to 55% of patients, coronary artery dilation or aneurysms in 12% to 21%, myocarditis in 17% to 18%, elevated troponin and BNP or NT-proBNP, or pericardial effusion in 23% of the patients. 14,35,57,80 Arrhythmias, heart block, and other electrocardiographic abnormalities (eg, ST-segment changes, QTc prolongation, and premature atrial and ventricular contractions) are less common findings but have been described. 20,83,84 Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C. 14,35 Patients with MIS-C have a higher neutrophil/lymphocyte ratio and lower platelet counts than those with non–MIS-C febrile illnesses.…”

“…20,83,84 Acute-phase reactants, including C-reactive protein, D-dimer, ferritin, and fibrinogen, can be significantly elevated in MIS-C. 14,35 Patients with MIS-C have a higher neutrophil/lymphocyte ratio and lower platelet counts than those with non–MIS-C febrile illnesses. 35,80…”