A Clinical Differentiation of Multisystem Inflammatory Syndrome in Children (MIS-C) & Kawasaki Disease (KD)

Background: With the emergence of the COVID 19 pandemic, a new disease, Multisystem Inflammatory Syndrome in Children (MIS-C), has evolved. Increasing numbers of children are being reported to have MIS-C in the U.S. & worldwide. In the U.S., there are currently 2617 MISC cases reported. MIS-C & Kawasaki Disease (KD) have almost the same presentation, making clinical differentiation difficult. This study aims at differentiating KD & MIS-C, which could assist clinicians to determine which disease they could be dealing with in their practices.

Methods: Clinical features & laboratory values were collected from published studies found by queries on PubMed & other websites. Reported values were selected from published systemic reviews, meta-analyses, & large retrospective chart studies.

Results: In KD, the most prevalent clinical features are fever (100%) & the 5 KD-defining clinical features: oral mucosal changes (96.5%), rash (96%), non-purulent conjunctivitis (89%), extremity changes (75.6%), and cervical lymphadenopathy (62.7%). MIS-C also presents with fever (100%) but has lower prevalence of oral mucosal changes (23%), rash (38.2%), non-purulent conjunctivitis (44.0%), extremity changes (2.5%), & cervical lymphadenopathy (4%). MIS-C leads to higher rates of ventricular dysfunction (39.3%), myocarditis (23%), & shock.
For cardiac biomarkers, MIS-C has elevated troponin I (x6 normal) & Beta Natriuretic Peptide (BNP) (x414 normal), while KD has elevations of troponin I (x1.9 normal) & BNP (x15 normal).
MIS-C has higher elevations in ESR, CRP, and D-Dimer at x6, x30, and x40 from the normal values, respectively, while KD has elevations of x2.8, x2.1, x7.3 from the normal values, respectively. MIS-C is associated with neutrophilia, thrombocytopenia, & anemia in 22% of cases. KD is associated with mild neutrophilia & anemia. KD has thrombocytosis in the subacute phase (x1.46 normal).

Conclusion: Our results demonstrated that there are overlaps & differences in clinical and laboratory features. Fever is present in both KD & MIS-C, however the 5 KD defining clinical features of KD are less frequent in MIS-C.
MIS-C induces higher levels of troponin I & BNP, findings that could potentially explain for higher rates of ventricular dysfunction & myocarditis.
MIS-C causes higher elevations in inflammatory markers & D-Dimers compared to KD. Uniquely, thrombocytopenia is commonly present in MISC rather than in KD.
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 &, therefore, deliver the most appropriate care to patients in their practices.