Which signs separate MIS-C from COVID-19, Kawasaki disease, toxic shock syndrome?

Children with multisystem inflammatory syndrome in children (MIS-C) show significantly higher prevalence of cardiac complications, elevated markers of inflammation and cardiac damage, thrombocytopenia, and lymphopenia than do those with COVID-19, Kawasaki disease (KD), and toxic shock syndrome (TSS), reports a study.

“MIS-C can be challenging to differentiate from COVID-19 and other hyperinflammatory conditions,” the researchers said. “In patients with substantial overlap in clinical manifestation, the diagnostic scores can be a valuable tool for distinguishing MIS-C from COVID-19, KD, and TSS.”

Data from patients aged <21 years hospitalized with MIS-C, COVID-19, KD, and TSS in four major healthcare institutions were obtained. The researchers compared patient demographics and clinical and laboratory data among the four conditions. Finally, they developed a diagnostic scoring tool to assist in clinical diagnosis.

Of the patients, 233 were diagnosed with MIS-C, 102 with COVID-19, 101 with KD, and 76 with TSS. Those with MIS-C had the highest prevalence of decreased cardiac function (38.6 percent), myocarditis (34.3 percent), pericardial effusion (38.2 percent), mitral regurgitation (31.8 percent), and pleural effusion (34.8 percent) relative to other conditions. [Pediatr Infect Dis J 2022;41:315-323]

In addition, MIS-C patients had elevated peak levels of C-reactive protein and reduced platelets and lymphocyte nadir counts compared with COVID-19 and KD patients, and increased levels of troponin, brain natriuretic peptide, and probrain natriuretic peptide than those with COVID-19.

Diagnostic scores that utilized clinical findings were effective at identifying MIS-C from COVID-19, KD, and TSS, with interval validation showing area under the curve ranging from 0.87 to 0.97.

“MIS-C, COVID-19, KD, and TSS are all conditions with the potential for multisystem involvement and systemic inflammation, yet they are distinct disorders with potentially different underlying pathophysiology that require different approaches for clinical management,” the researchers said.

Accurate diagnosis

Common manifestations of MIS-C included diarrhoea, abdominal pain, neck pain, myocarditis, pericardial effusion, mitral regurgitation, pleural effusion, and reduced cardiac function. Myocarditis, pericardiac and pleural effusion, mitral regurgitation, and decreased cardiac function appeared almost exclusively in MIS-C patients. [BMJ 2021;372:n385]

COVID-19 patients had the highest prevalence of cough, shortness of breath, and pneumonia and the lowest rates of cardiovascular complications and dermatologic symptoms. Patients with KD showed more dermatologic symptoms and fewer shock, hypotension, respiratory complications, and renal injury. Moreover, patients with TSS had the highest rates of shock, hypotension, and renal injury.

“The findings in this study present similar results to previously published studies comparing MIS-C with KD, KD shock, and TSS,” the researchers said. “Patients with MIS-C were more likely to be male and younger in age compared with patients with COVID-19.” [Front Pediatr 2021;109:1-8; JAMA 2020;324:259-269]

Treatment for each condition differs from the others, which is why ensuring the correct diagnosis is necessary to the administration of quick and appropriate clinical management. The diagnostic score is a helpful tool in warranting timely and accurate diagnosis of MIS-C in patients who may have clinical overlap with the other conditions, according to the researchers.

“The diagnostic scores go beyond the case definition to help clinicians evaluate patients’ diagnosis based on the totality of available clinical and laboratory data in patients with overlapping features,” the researchers said. “The diagnostic scores are not intended to assist with determining whether the case meets the MIS-C case definition for reporting purposes.”