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Evidence Based Strategies for Common Clinical Questions

April 2022

MISConceptions of KD and MIS-C


Author: Michelle Brown, DO | Chief Resident of Pediatrics


Column Editor: Kathleen Berg, MD | Co-Director, Department of Evidence Based Practice | Pediatric Hospitalist, Division of Pediatric Hospital Medicine | Associate Professor of Pediatrics, UMKC School of Medicine 


A 5-year-old patient presents to their pediatrician’s office with prolonged fever in the setting of conjunctival injection, rash, adenopathy, hand and feet edema and desquamation. With this constellation of signs, Kawasaki disease (KD) would historically be considered the most likely diagnosis. However, since the SARS-CoV-2 pandemic, the identification of multisystem inflammatory syndrome in children (MIS-C) has caused providers to reconsider the differential. The aim of this article is to briefly highlight similarities and differences between KD and MIS-C, providing guidance to outpatient clinicians on when to suspect each condition and what to anticipate in follow-up.

KD is a leading cause of acquired heart disease in developed countries and the second most common vasculitis, following Henoch-Schonlein purpura, in the pediatric population.1,2 Though not fully understood, KD largely impacts medium size arteries, resulting in systemic inflammation which manifests as persistent fever, rash, mucus membrane involvement, conjunctivitis, hand and feet edema and desquamation, and cervical lymphadenopathy. With the surge of SARS-CoV-2, post-viral sequelae surfaced in the pediatric population, one of which can mimic KD with these same signs. In April 2020, the first case of MIS-C was reported and shared several characteristic findings of KD, making the two challenging to differentiate. Since then, immunopathology implicated in these two disease processes have been examined. While there are likely differences in T cell subsets, interleukin-17A, and autoantibodies, additional study is needed to further elucidate immunologic differences.3

KD and MIS-C have several overlapping signs and symptoms, making it challenging for providers to differentiate diagnoses and provide anticipatory guidance. Over the past two years, studies have highlighted differences regarding age, symptomatology and laboratory values. Age: Approximately 75% of patients diagnosed with KD are less than 5 years of age; in contrast, patients diagnosed with MIS-C are older children and teenagers, with median ages 6-10.4 Symptoms: Patients with MIS-C tend to present with gastrointestinal symptoms, including abdominal pain, vomiting and diarrhea.5 Furthermore, they have higher prevalence (33%-87%) of hemodynamic instability (i.e., hypotension and depressed ventricular systolic function) requiring vasopressor support versus only 2%-7% of those with KD. Laboratory: Those with MIS-C often present with lymphopenia and thrombocytopenia versus thrombocytosis after day 7 of illness that is typically seen in KD. Ferritin and D-dimer are markedly elevated in MIS-C compared to grossly unremarkable in KD.4 While most patients with MIS-C have IgG antibodies for SARS-CoV-2,4 they could also be present in a patient with KD who had a prior infection. Both conditions can cause coronary artery dilation or aneurysms, though cardiac markers of inflammation (troponin and brain natriuretic peptide) are more significantly elevated in MIS-C, suggesting a higher degree of myocardial involvement. In fact, per Alsaied et al., patients with MIS-C have higher rates of coronary artery aneurysms, ventricular dysfunction, and arrhythmias than those with KD.6

Treatment depends on which diagnosis is more likely and may include intravenous immunoglobulin, corticosteroids, aspirin, and/or immunomodulators. However, for either diagnosis, follow-up is essential. Primary care physicians play a vital role in short- and long-term management following KD or MIS-C. While a greater body of evidence allows for guideline-driven treatment and follow-up for KD,7 much less is known about MIS-C. Cardiology management is tailored to the initial insult, but may include serial echocardiograms, EKGs, a Holter monitor study, exercise restrictions and laboratory follow-up. In a study by Penner et al., a subset of MIS-C patients was followed for six months after diagnosis. Sequelae of gastrointestinal symptoms, abnormal echocardiograms and abnormal hematological findings were largely resolved by six months, while weakness and reduced exercise tolerance persisted in some patients. Most patients returned to academic requirements within six months.8 These findings highlight the important role of primary care providers in monitoring and ensuring appropriate subspecialty follow-up throughout the course of MIS-C.

While KD and MIS-C share many physical exam signs, several symptoms and laboratory findings can help differentiate the two conditions. The Children’s Mercy MIS-C Care Process Model helps guide clinicians through initial assessment. Recognizing nuances between these two conditions is key to appropriate initial management, cardiac surveillance, and follow-up to mitigate the risk of short- and long-term sequelae.



  1. Younger DS. Epidemiology of the vasculitides. Neurol Clin. 2019;37(2):201-217. doi:10.1016/j.ncl.2019.01.016
  2. Menikou S, Langford PR, Levin M. Kawasaki disease: the role of immune complexes revisited. Front Immunol. 2019;10:1156. Published online June 12, 2019. doi:10.3389/fimmu.2019.01156
  3. Consiglio CR, Cotugno N, Sardh F, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183(4):968-981.e7. doi:10.1016/j.cell.2020.09.016
  4. Zhang QY, Xu BW, Du JB. Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: clinical presentations, diagnosis, and treatment. World J Pediatr. 2021;17(4):335-340. doi:10.1007/s12519-021-00435-y
  5. Zou H, Lu J, Liu J, et al. Characteristics of pediatric multi-system inflammatory syndrome (PMIS) associated with COVID-19: a meta-analysis and insights into pathogenesis. Int J Infect Dis. 2021;102:319-326. doi:10.1016/j.ijid.2020.11.145
  6. Alsaied T, Tremoulet AH, Burns JC, et al. Review of cardiac involvement in multisystem inflammatory syndrome in children. Circulation. 2021;143(1):78-88. doi:10.1161/CIRCULATIONAHA.120.049836
  7. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association [published correction appears in Circulation. 2019 Jul 30;140(5):e181-e184]. Circulation. 2017;135(17):e927-e999. doi:10.1161/CIR.0000000000000484
  8. Penner J, Abdel-Mannan O, Grant K, et al. 6-month multidisciplinary follow-up and outcomes of patients with paediatric inflammatory multisystem syndrome (PIMS-TS) at a UK tertiary paediatric hospital: a retrospective cohort study. Lancet Child Adolesc Health. 2021;5(7):473-482. doi:10.1016/S2352-4642(21)00138-3