Overlap in Clinical Features of MIS-C, Kawasaki Disease Complicates Diagnosis


Fever is present in both KD and MIS-C, but there is lower prevalence of the 5 KD defining clinical features in MIS-C.

Andersen L. Estes, MS-IV

Andersen L. Estes, MS-IV

During the rise of the 2020 pandemic caused by Sars-CoV-2, data has shown a concurrent increase in the evolution of Multisystem Inflammatory Syndrome in Children (MIS-C).

At the same time, MIS-C and Kawasaki Disease (KD) are similar in their clinical presentation, often making differentiation difficult in the diagnosis process.

As a result, a team of investigators, led by Andersen L. Estes, MS-IV, Quillen College of Medicine, East Tennessee State University looked to highlight both clinical presentations and studies to assist clinicians in the differentiation of both MIS-C and KD, in order to determine appropriate treatment and follow-up for patients in clinical care.

The new research was presented at the 2021 American Academy of Pediatrics Virtual Meeting.


Previous data show there are nearly 5000 (n = 4661) cases of MIS-C in the United States as of August 2021.

Investigators collected data on clinical features and laboratory values from published studies on Pubmed and other websites, as well as citations in articles until March 2021.

Additionally, reported values were gathered from a combination of published systematic reviews, meta-analyses and large retrospective chart studies.

The team noted that KD required fever and 4 of 5 additional signs for diagnosis, out of fever and oral mucosal changes, rash, non-purulent conjunctivitis, extremity changes, and cervical lymphadenopathy.

Further, MIS will also present with fever and symptoms 2 - 4 weeks following SARS-CoV-2 infection. Both MIS-C and KD are shown to have cardiac complications.

What were the findings?

Estes and colleagues found the most prevalent clinical features in KD were fever (100%), followed by oral mucosal changes (96.5%), rash (96%), non-purulent conjunctivitis (89%), extremity changes (75.6%), and cervical lymphadenopathy (62.7%).

They observed a similar high fever rate in MIS-C (92%), but observed lower prevalence of oral mucosal changes (23%), rash (38%), non-purulent conjunctivitis (44%), extremity changes (3%), & cervical lymphadenopathy (4%).

In addition, higher rates of ventricular dysfunction (39.3%), myocarditis (23%), and coronary aneurysms (13) were observed in MIS-C compared to KD.

Investigators also observed that both MIS-C and KD can present with abdominal pain, showing patients with MIS-C are more likely to present with abdominal pain (53%) in comparison to patients with KD (21%).

In cardiac biomarkers, data show MIS-C has elevated troponin I (x6 fold relative to normal) and Beta Natriuretic Peptide (BNP) (x414 relative to normal), while KD showed elevated levels of troponin I (x 1.9 relative to normal) and BNP (x15 relative to normal)

Moreover, MIS showed higher elevations in ESR (x6), CRP (x30), and D-DImer (x40) from normal values in comparison to KD.

Associations were also observed with neutrophilia,thrombocytopenia and anemia in 22% of MIS-C cases, while KD is associated with thrombocytosis in the subacute phase (x1.46 relative to normal).

What are the takeaways?

In their conclusion, investigators noted there are overlaps in features of both conditions, considering fever is present in both MIS-C and KD, but the 5 signs for diagnosis of KD showed less frequency in MIS-C.

“Differentiating KD & MIS-C can be challenging, but by focusing closely on the clinical & laboratory features, clinicians may be able to distinguish between the two and therefore, deliver the most appropriate care to patients in their practices,” investigators wrote.

The study, “A Clinical Differentiation of Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki Disease (KD),” was published online by AAP 2021.

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