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Top 10: May 9

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By Christian Hoffmann &
Bernd S. Kamps

9 May

Top 10 Special on

Kawasaki-like syndrome in children

March/April 2020

A new twist in this new pandemic: at the end of March 2020, Jones et al. described the case of a six-month-old baby girl with fever, rash and swelling characteristic of a rare pediatric inflammatory condition, Kawasaki syndrome (Jones 2020). The child is treated according to treatment guidelines with a single dose of 2g/kg intravenous immunoglobulin and high dose acetylsalicylic 20mg/kg four times daily. The fever breaks within hours.

A month later, on 27 April, the National Health Service (NHS) sends an email alert to members of the British Paediatric Critical Care Society (PICS) highlighting “a small rise in the number of cases of critically ill children presenting with an unusual clinical picture.” Many of these children have tested positive for COVID-19, while some had not. The alert indicates that “the cases have in common overlapping features of toxic shock syndrome and atypical Kawasaki disease with blood parameters consistent with severe COVID-19 in children. Abdominal pain and gastrointestinal symptoms have been a common feature as has cardiac inflammation”, (see the PICS statement).

A few days later, Sylvain Renolleau, head of the intensive care unit at Necker hospital, Paris, reports more than 20 children and adolescents 3 to 17 years old hospitalized in intensive care. The first cases were seen around 15 April. Symptoms included abdominal pain, diarrhea and vomiting, sometimes fever, myocarditis, and a strong inflammatory syndrome. Although not all children tested positive for SARS-CoV-2, all seem to have been in contact with the virus. No deaths have been reported so far. At the end of April, nearly 100 cases had been found in children in France, Great Britain, Italy, Spain, Switzerland and the United States.

On 1 May 2020, the Royal College of Paediatrics and Child Health released guidance describing a systemic inflammatory response sharing “common features with other pediatric inflammatory conditions including: Kawasaki disease, staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis, and macrophage activation syndromes (Royal College of Paediatrics and Child Health 2020).” On 4 May, New York City’s Department of Health issued a similar alert (NYC Health 2020). Two days later, 64 cases were reported from New York (New York Department of Health 2020).

Kawasaki Disease

Kawasaki disease (KD) is an acute-onset systemic vasculitis of medium-sized vessels that mostly affects infants and toddlers (Hedrich 2017).

The first English-language report of 50 patients goes back to Tomisaku Kawasaki in 1974 (Kawaski 1974, Burns 2000). The KD incidence is much higher in Northeast Asian countries including Japan, South Korea, China, and Taiwan, 10–30 times higher than that of KD in North America and Europe (see the world map in Kim GB 2019).

More than 90% of children were less than 5 years old in a study from Inner Mongolia (Zhu 2015). Untreated, KD leads to coronary artery aneurysms in around 25% of cases (don’t miss this paper: McCrindle 2017). The diagnosis of “classic KD” is based on the presence of ≥5 days of fever plus four out of five diagnostic criteria including erythema of the lips or mouth, trunk rash, swelling or erythema of the hands or feet, conjunctivitis, and lymph node swelling (see the detailed discussion in McCrindle 2017).

Prompt diagnosis is essential, immune globulin being the mainstay of initial treatment. Even in these COVID-19 times, physicians should keep an eye out for KD in all children with prolonged fever, especially in those younger than 1 year (Harasheh 2020).

The cause of KD remains unknown. Some lines of evidence point to a post-infectious trigger causing hyperreaction of the immune system (Dietz 2017) and an association between viral respiratory infections and KD (Jordan-Villegas 2010, Kim JH 2012, Turnier 2015). The primarily winter-spring KD seasonality and well-documented Japanese epidemics with wave-like spread also support an infectious trigger (Rowley 2018).

The Future

It is still unknown if there is a correlation between the cases described above and COVID-19. If there is a correlation, it is unclear whether COVID-19-associated inflammatory disorder and Kawasaki disease are identical (COVID-19-associated cases seem to have more severe abdominal pain, nausea and vomiting; those with severe shock are often older than the typical Kawasaki patients; and in Kawasaki cases, heart vessels seem to be more involved).

Summary

  • A new Kawasaki-like syndrome may be emerging in children of all ages.
  • The syndrome is rare.
  • This syndrome may be related to SARS-CoV-2 but could as well be related to a different infectious pathogen with similar characteristics.
  • So far, little is known about the new syndrome.
  • To be remembered: serious COVID-19 complications are very rare among children. Throughout Europe, SARS-CoV-2 has caused very few victims among children. In Britain, only 9 children aged 0 to 19 have died after testing positive for coronavirus (0.05% of the 21,678 deaths recorded at the end of April).

See also selected press articles from France (Le Monde, Libération), UK (The Guardian), Spain (El País), Italy (Corriere della Sera) and Germany (FAZ).

References

Burns JC, Kushner HI, Bastian JF, et al. Kawasaki disease: A brief history. Pediatrics. 2000 Aug;106(2):E27. PubMed: https://pubmed.gov/10920183. Full-text: https://pediatrics.aappublications.org/content/106/2/e27

Dietz SM, van Stijn D, Burgner D, et al. Dissecting Kawasaki disease: a state-of-the-art review. Eur J Pediatr. 2017 Aug;176(8):995-1009. PubMed: https://pubmed.gov/28656474. Full-text: https://doi.org/10.1007/s00431-017-2937-5

Harahsheh AS, Dahdah N, Newburger JW, et al. Missed or Delayed Diagnosis of Kawasaki Disease During the 2019 Novel Coronavirus Disease (COVID-19) Pandemic. J Pediatr. 2020 Apr 23. pii: S0022-3476(20)30556-4. PubMed: https://pubmed.gov/32370951. Full-text: https://doi.org/10.1016/j.jpeds.2020.04.052

Hedrich CM, Schnabel A, Hospach T. Kawasaki Disease. Front Pediatr. 2018 Jul 10;6:198. PubMed: https://pubmed.gov/30042935. Full-text: https://doi.org/10.3389/fped.2018.00198

Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp Pediatr. 2020 Apr 7. pii: hpeds.2020-0123. PubMed: https://pubmed.gov/32265235. Full-text: https://hosppeds.aappublications.org/content/hosppeds/early/2020/04/06/hpeds.2020-0123.full.pdf – This is the first report about Kawasaki disease and concurrent SARS-CoV-2 infection. The authors describe the case of a a six-month-old baby girl with fever, rash and swelling characteristic of Kawasaki syndrom. The child had minimal respiratory symptoms. She was treated with a single dose of 2g/kg intravenous immunoglobulin (IVIG) and high dose acetylsalicylic acid (ASA 20mg/kg four times daily) according to treatment guidelines.

Jordan-Villegas A, Chang ML, Ramilo O, Mejias A. Concomitant respiratory viral infections in children with Kawasaki disease. Pediatr Infect Dis J. 2010 Aug;29(8):770-2. PubMed: https://pubmed.gov/20354462. Full-text: https://doi.org/10.1097/INF.0b013e3181dba70b

Kawaski T, Kosaki F, Okawa S, et al (1974) A new infantile acute febrile mucocutaneous lymph node syndrome (MCLS) prevailing in Japan. Pediatrics 54:271–276. Full-text: https://pediatrics.aappublications.org/content/pediatrics/54/3/271.full-text.pdf

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 Dec;55(12):470-3. PubMed: https://pubmed.gov/23300502. Full-text: https://doi.org/10.3345/kjp.2012.55.12.470

Kim GB. Reality of Kawasaki disease epidemiology. Korean J Pediatr. 2019 Aug;62(8):292-296. PubMed: https://pubmed.gov/31319643. Full-text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702118/

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. Circulation. 2017 Apr 25;135(17):e927-e999. PubMed: https://pubmed.gov/28356445. Full-text: https://doi.org/10.1161/CIR.0000000000000484

New York City’s Department of Health. 2020 Health Alert #13: Pediatric Multi-System Inflammatory Syndrome Potentially Associated with COVID-19. 4 May 2020 (accessed 6 May 2020). Document: https://www1.nyc.gov/assets/doh/downloads/pdf/han/alert/2020/covid-19-pediatric-multi-system-inflammatory-syndrome.pdf

New York Departement of Health. Healthadvisory: pediatric multi-system inflammatory syndrome potentially associated with coronavirus disease (covid-19) in children. 6 May 2020 (accessed 9 May 2020). Document: http://dmna.ny.gov/covid19/docs/all/DOH_COVID19_PediatricInflammatorySyndrome_050620.pdf

Paediatric Critical Care Society. PICS Statement: Increased number of reported cases of novel presentation of multi-system inflammatory disease. 27 April 2020 (accessed 7 May 2020). Document: https://picsociety.uk/wp-content/uploads/2020/04/PICS-statement-re-novel-KD-C19-presentation-v2-27042020.pdf

Rowley AH, Shulman ST. The Epidemiology and Pathogenesis of Kawasaki Disease. Front Pediatr. 2018 Dec 11;6:374. PubMed: https://pubmed.gov/30619784. Full-text: https://doi.org/10.3389/fped.2018.00374

Royal College of Paediatrics and Child Health. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. 1 May 2020 (accessed 4 May). Document: https://www.rcpch.ac.uk/resources/guidance-paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19

Turnier JL, Anderson MS, Heizer HR, Jone PN, Glode MP, Dominguez SR. Concurrent Respiratory Viruses and Kawasaki Disease. Pediatrics. 2015 Sep;136(3):e609-14. PubMed: https://pubmed.gov/26304824. Full-text: https://doi.org/10.1542/peds.2015-0950

Zhu H, Yu SF, Bai YX, Liang YY, Su XW, Pan JY. Kawasaki disease in children: Epidemiology, clinical symptoms and diagnostics of 231 cases in 10 years. Exp Ther Med. 2015 Jul;10(1):357-361. PubMed: https://pubmed.gov/26170962. Full-text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486877/