What are the Main Differences Between MIS-C and Kawasaki Disease?

Patient Presentation
The residents were talking before their continuity clinic and noted that 2 young teen patients had been recently admitted to the pediatric intensive care unit with multisystem inflammatory syndrome in children (MIS-C). “We had to put one of them on ECMO yesterday and today she is much more stable, but she still looks pretty bad,”” one resident remarked. “I was cross-covering a few days ago and saw the other patient. He looks worse than the Kawasaki Disease patient who wasn’t responding to IVIG I saw the week before,” she said. The attending knew that these diseases probably had similar underlying origins but wasn’t sure of the main differences between the two, so he reviewed the Centers for Disease Control current information about MIS-C.

SARS-CoV-2 or COVID-19 was first observed in Wuhan China in late 2019. By March 2020 it had spread to become a world-wide pandemic and continues today despite vaccination and other public health measures. Early on people were worried that children would be the major age group affected, but the major groups were older individuals and those with underlying health problems. That is not to say that children are not affected as they were and could have severe disease. However as an overall group, they tend to get the virus and have less severe symptoms than adults. Severe disease is about 1% of pediatric cases compared to 10-20% for adults, and pediatric mortality is estimated at < 0.1% compared to 5-15% for adults.

Common presentations of COVID-19 in children include:

  • *Fever/chills
  • *Cough
  • *Diarrhea
  • Fatigue
  • Headache
  • Myalgia
  • Nausea/emesis
  • *Pharyngitis
  • Rhinorrhea
  • Anosmia/aguesia

* = very common symptoms especially for mild disease.

In April 2020 there were warnings “…about cases of older school-aged children and adolescents presenting with fever, hypotension, severe abdominal pain and cardiac dysfunction….”These children had laboratory findings of cytokine storm….Almost all of these children no longer required intensive care after only a few days and completely recovered, although rare deaths [occurred]….” These children and adolescents had a new condition called multisystem inflammatory syndrome in children or MIS-C. MIS-C has clinical similarities to Kawasaki Disease (KD) which is a medium-vessel vasculitis presenting predominantly with fever, lymphadenopathy, rash and mucositis. It’s etiology is undetermined but likely is viral. A brief review can be found here. There are different case definitions of MIS-C (see To Learn More below for references) with overlap with other problems such as KD, juvenile idiopathic arthritis (systemic onset), toxic shock syndrome other viral infections and inflammatory conditions of children.

Learning Point
Key differences between MIS-C and Kawasaki Disease include:

MIS-C Kawasaki Disease
Age Older children and adolescents, 8-10 years is common Generally < 5 years, peak ~10 months
Gender Male > Female Male > Female
Race/Ethnicity African/Hispanic/Latino > White East Asian
Labs High inflammatory markers and cytokine storm including leukopenia, high ventricular natriuretic peptide Not found, has neutrophilic leukocytosis usually
Fever Present Present
Respiratory symptoms Little Not present
Lymphadenopathy Not common More common
Skin Rash similar to KD but only seen < 50% of time Typical rash seen in most patients
Usual presentations Multiorgan system failure, Gastrointestinal problems incl. abdominal pain and diarrhea Does not have multiorgan system failure, GI symptoms usually not present
Cardiovascular problems Cardiac dysfunction seen when presenting especially with hemodynamic compromise, myocarditis and pericarditis, coronary artery aneurysms can be seen but small size or dilatation only Myocarditis is not common, usually not hemodynamically unstable at presentation, coronary artery aneurysms and dilatation are seen
Response to IVIG Often does not respond Usually responds

Questions for Further Discussion
1. What resources do you use to keep current with COVID-19 information and other emerging/emerged medical problems?
2. What are current treatments for MIS-C?
3. How does MIS-C differ from toxic shock syndrome?
4. What is the long term outcome of children with MIS-C?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: COVID-19.
To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol. Published online June 16, 2020:1-2. doi:10.1038/s41577-020-0367-5

Kabeerdoss J, Pilania RK, Karkhele R, Kumar TS, Danda D, Singh S. Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management. Rheumatol Int. Published online November 21, 2020:1-14. doi:10.1007/s00296-020-04749-4

Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 2. Arthritis Rheumatol. 2021;73(4):e13-e29. doi:10.1002/art.41616

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa