Kawasaki Disease and Multisystem Inflammatory Syndrome in Children: An Overview and Comparison

 

Am Fam Physician. 2021 Sep ;104(2):244-252.

Published online August 12, 2021.

Author disclosure: No relevant financial affiliations.

Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) are inflammatory conditions that present diagnostic and therapeutic challenges to the physician. Although many of their features overlap, they are two distinct conditions. KD is a febrile illness most commonly affecting children younger than five years. It manifests with prolonged fever and at least four of the following features: bilateral bulbar conjunctivitis, mucositis, diffuse maculopapular rash, extremity changes, and cervical lymphadenopathy of 1.5 cm or more in diameter. Patients with MIS-C may have many of the same manifestations but tend to have higher rates of gastrointestinal and neurocognitive symptoms and signs of shock on presentation. Both conditions are associated with cardiac sequelae, including coronary artery aneurysms, although children with MIS-C are at high risk of developing ventricular dysfunction and depressed cardiac output. Lymphocytopenia, thrombocytopenia, elevated troponin, and elevated B-type natriuretic peptide are key laboratory findings of MIS-C that can help distinguish it from KD. The use of intravenous immune globulin is well established in KD and also appears to have a role in the treatment of MIS-C. Aspirin has been used in KD for an anti-inflammatory effect, and low-dose aspirin is recommended for MIS-C to reduce the risk of thrombosis. In addition to supportive care, patients with MIS-C may benefit from immunomodulatory medications, although data on this topic are evolving.

First described in Japan in 1967, Kawasaki disease (KD) is a vasculitis affecting small- and medium-sized vessels; it is predominantly seen in children younger than five years.1 This febrile illness is characterized by systemic inflammation and is the most common cause of acquired coronary artery disease in children.2 With the emergence of multisystem inflammatory syndrome in children (MIS-C), a new inflammatory syndrome associated with COVID-19, KD has received increased attention because features of the diseases overlap.

 Enlarge     Print

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComments

A diagnosis of classic KD is made in the presence of prolonged fever (five or more days) and four or more of the following principal features: oral mucosal inflammation; bilateral bulbar conjunctivitis; a diffuse maculopapular rash; extremity changes, including erythema and edema of the hands and feet; and cervical lymphadenopathy of 1.5 cm or more in diameter.2

C

Consensus opinion, society guidelines

For patients with a suspected diagnosis of KD or MIS-C, echocardiography should be performed promptly but should not delay treatment.2,7

C

Expert guidelines that included studies in limited populations and with few randomized controlled trials; benefits greatly outweigh risks

Physicians concerned about MIS-C should pursue a diagnostic workup that includes complete blood count, complete metabolic panel, erythrocyte sedimentation rate, C-reactive protein, and SARS-CoV-2 polymerase chain reaction and/or serologies; additional workup may be necessary, including B-type natriuretic peptide, troponin, ferritin, prothrombin time, partial thromboplastin time, d dimer, fibrinogen, lactate dehydrogenase, cytokine panel, electrocardiography, and chest radiography.19

C

Expert opinion, society guidelines

Patients with KD should receive IVIG (2 g per kg given as a single dose).2,2024

C

Multiple randomized controlled trials and meta-analyses looking at coronary artery abnormalities

Suspected cases of MIS-C should be referred promptly to the hospital. Management of MIS-C requires a multidisciplinary team of specialists including, but not limited to, pediatric critical care physicians, pediatric cardiologists, pediatric hospitalists, pediatric rheumatologists, pediatric infectious disease specialists, and pediatric hematologists.19

C

Expert opinion

Patients with MIS-C should receive IVIG (2 g per kg given as a single dose), and concurrent corticosteroids should be considered.19

C

Expert opinion, observational studies


IVIG = intravenous immune globulin; KD = Kawasaki disease; MIS-C = multisystem inflammatory syndrome in children.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

The Authors

show all author info

JOHN B. DARBY, MD, is an assistant professor in the Department of Pediatrics at Wake Forest School of Medicine, Winston-Salem, N.C....

JENNIFER M. JACKSON, MD, is the assistant dean for Curricular Innovation and an associate professor in the Department of Pediatrics at Wake Forest School of Medicine.

Address correspondence to Jennifer M. Jackson, MD, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157 (email: jstancil@wakehealth.edu). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

References

show all references

1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children [in Japanese]. Arerugi. 1967;16(3):178–222....

2. McCrindle BW, Rowley AH, Newburger JW, et al.; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Epidemiology and Prevention. 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;140(5):e181–e184]. Circulation. 2017;135(17):e927–e999.

3. Turnier JL, Anderson MS, Heizer HR, et al. Concurrent respiratory viruses and Kawasaki disease. Pediatrics. 2015;136(3):e609–e614.

4. Esper F, Shapiro ED, Weibel C, et al. Association between a novel human coronavirus and Kawasaki disease. J Infect Dis. 2005;191(4):499–502.

5. Holman RC, Belay ED, Christensen KY, et al. Hospitalizations for Kawasaki syndrome among children in the United States, 1997–2007. Pediatr Infect Dis J. 2010;29(6):483–488.

6. Holman RC, Curns AT, Belay ED, et al. Kawasaki syndrome hospitalizations in the United States, 1997 and 2000. Pediatrics. 2003;112(3 pt 1):495–501.

7. Centers for Disease Control and Prevention. Multisystem inflammatory syndrome (MIS). Updated June 25, 2021. Accessed July 14, 2021. https://www.cdc.gov/mis/hcp/index.html

8. Kaushik A, Gupta S, Sood M, et al. A systematic review of multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection. Pediatr Infect Dis J. 2020;39(11):e340–e346.

9. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395(10239):1771–1778.

10. Cheung EW, Zachariah P, Gorelik M, et al. Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City. JAMA. 2020;324(3):294–296.

11. Whittaker E, Bamford A, Kenny J, et al.; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. 2020;324(3):259–269.

12. Kanegaye JT, Van Cott E, Tremoulet AH, et al. Lymph-node-first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr. 2013;162(6):1259–1263, 1263.e1–1263-.e2.

13. Kim JH, Yu JJ, Lee J, et al. Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease. Korean J Pediatr. 2012;55(12):470–473.

14. Freeman AF, Shulman ST. Kawasaki disease: summary of the American Heart Association guidelines. Am Fam Physician. 2006;74(7):1141–1148. Accessed July 5, 2021. https://www.aafp.org/afp/2006/1001/p1141.html

15. Printz BF, Sleeper LA, Newburger JW, et al.; Pediatric Heart Network Investigators. Noncoronary cardiac abnormalities are associated with coronary artery dilation and with laboratory inflammatory markers in acute Kawasaki disease. J Am Coll Cardiol. 2011;57(1):86–92.

16. Sperotto F, Friedman KG, Son MBF, et al. Cardiac manifestations in SARS-CoV-2-associated multisystem inflammatory syndrome in children: a comprehensive review and proposed clinical approach. Eur J Pediatr. 2021;180(2):307–322.

17. Belay ED, Abrams J, Oster ME, et al. Trends in geographic and temporal distribution of US children with multisystem inflammatory syndrome during the COVID-19 pandemic. JAMA Pediatr. 2021;175(8):837–845.

18. Choi NH, Fremed M, Starc T, et al. MIS-C and cardiac conduction abnormalities. Pediatrics. 2020;146(6):e2020009738.

19. 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.

20. Furusho K, Kamiya T, Nakano H, et al. High-dose intravenous gamma-globulin for Kawasaki disease. Lancet. 1984;2(8411):1055–1058.

21. Newburger JW, Takahashi M, Burns JC, et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med. 1986;315(6):341–347.

22. Terai M, Shulman ST. Prevalence of coronary artery abnormalities in Kawasaki disease is highly dependent on gamma globulin dose but independent of salicylate dose. J Pediatr. 1997;131(6):888–893.

23. Mori M, Miyamae T, Imagawa T, et al. Meta-analysis of the results of intravenous gamma globulin treatment of coronary artery lesions in Kawasaki disease. Mod Rheumatol. 2004;14(5):361–366.

24. Oates-Whitehead RM, Baumer JH, Haines L, et al. Intravenous immunoglobulin for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2003;(4):CD004000.

25. Baumer JH, Love SJL, Gupta A, et al. Salicylate for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2006;(4):CD004175.

26. Dallaire F, Fortier-Morissette Z, Blais S, et al. Aspirin dose and prevention of coronary abnormalities in Kawasaki disease. Pediatrics. 2017;139(6):e20170098.

27. Son MBF, Newburger JW. Kawasaki disease. Pediatr Rev. 2018;39(2):78–90.

28. Kobayashi T, Saji T, Otani T, et al.; RAISE study group investigators. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial. Lancet. 2012;379(9826):1613–1620.

29. Chen S, Dong Y, Kiuchi MG, et al. Coronary artery complication in Kawasaki disease and the importance of early intervention: a systematic review and meta-analysis. JAMA Pediatr. 2016;170(12):1156–1163.

30. Friedman KG, Gauvreau K, Baker A, et al. Primary adjunctive corticosteroid therapy is associated with improved outcomes for patients with Kawasaki disease with coronary artery aneurysms at diagnosis. Arch Dis Child. 2021;106(3):247–252.

31. Sundel R. Kawasaki disease: initial treatment and prognosis. UpToDate. Accessed May 1, 2021. https://www.uptodate.com/contents/kawasaki-disease-initial-treatment-and-prognosis

32. Harwood R, Allin B, Jones CE, et al.; PIMS-TS National Consensus Management Study Group. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process [published correction appears in Lancet Child Adolesc Health. 2021;5(2):e5]. Lancet Child Adolesc Health. 2021;5(2):133–141.

33. Ouldali N, Toubiana J, Antona D, et al.; French Covid-19 Paediatric Inflammation Consortium. Association of intravenous immunoglobulins plus methylprednisolone vs immunoglobulins alone with course of fever in multisystem inflammatory syndrome in children [published correction appears in JAMA. 2021;326(1):90]. JAMA. 2021;325(9):855–864.

34. DeBiasi RL. Immunotherapy for MIS-C—IVIG, glucocorticoids, and biologics [editorial]. N Engl J Med. 2021;385(1):74–75.

35. McArdle AJ, Vito O, Patel H, et al.; BATS Consortium. Treatment of multisystem inflammatory syndrome in children. N Engl J Med. 2021;385(1):11–22.

36. Son MBF, Murray N, Friedman K, et al.; Overcoming COVID-19 Investigators. Multisystem inflammatory syndrome in children—initial therapy and outcomes. N Engl J Med. 2021;385(1):23–34.

37. Saguil A, Fargo M, Grogan S. Diagnosis and management of Kawasaki disease. Am Fam Physician. 2015;91(6):365–371. Accessed June 28, 2021. https://www.aafp.org/afp/2015/0315/p365.html

 

 

Copyright © 2021 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions

CME Quiz

More in AFP


Editor's Collections


Related Content


MOST RECENT ISSUE


Oct 2021

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article