Multisystem inflammatory syndrome in children

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Background

  • In April 2020 during the SARS-CoV-2 outbreak UK pediatricians alerted the National Health Service of a new systemic inflammatory condition similar to Kawasaki disease in children testing positive for the virus
  • Cases were then reported worldwide with patients admitted to ICUs in the USA4,5,10, Canada10Italy11, and UK2,3
  • Thought to be an immunologically mediated inflammatory syndrome associated with previous SARS-CoV-2 infection1
    • Cases occur 3-5.5 weeks after patients tested positive for SARS-CoV-2
  • While Kawasaki disease has a predilection for children of Asian descent, MIS-C seems to affect African American children more often9
    • Compared to Kawasaki patients are generally older (median age 8.6 vs 2.5)1 and had a predominance of GI symptoms
  • Patients with MIS-C are significantly more likely to present with dyspnea, vomiting, diarrhea, lymphopenia, and elevated LDH and and D-dimer compared to patients with COVID-19 without MIS-C 6

Epidemiology

  • Occurs in 2/100,000 persons under 214
  • In a systematic review published June 2020, 11/7780 (0.14%) COVID-19 positive children met the CDC’s criteria for MIS-C6

Clinical Features

Differential Diagnosis

Evaluation

  • Labs
    • CBC
      • Lymphopenia
      • Neutrophilia
    • CMP
      • Low albumin
    • Inflammatory markers (elevated)
      • CRP
      • ESR
      • Fibrinogen
      • Procalcitonin
      • D-dimer
      • Ferritin
      • LDH
      • IL-6
    • BNP
    • Troponin
  • Imaging
    • Chest X-ray/CT
      • May show bilateral patchy infiltrates or ground glass opacities
    • Echocardiogram to evaluate for LV dysfunction, coronary aneurysm/dilation

Case Definition

  • CDC12
    • An individual aged <21 years presenting with feveri, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND
    • No alternative plausible diagnoses; AND
    • Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms
      • iFever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
      • iiIncluding, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin
    • Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C
    • Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection
  • WHO13
    • Children and adolescents 0–19 years of age with fever > 3 days
    • AND two of the following:
      • a) Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet).
      • b) Hypotension or shock.
      • c) Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP),
      • d) Evidence of coagulopathy (by PT, PTT, elevated d-Dimers).
      • e) Acute gastrointestinal problems (diarrhoea, vomiting, or abdominal pain).
    • AND
      • Elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin.
    • AND
      • No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes.
    • AND
      • Evidence of COVID-19 (RT-PCR, antigen test or serology positive), or likely contact with patients with COVID-19.

Management

Complications

' Study Capone et al.1 Davies et al.3 Dufort et al.4 Fields et al.5 Lee et al.7 Shekerdemian et al.10
Complication (%) ICU admission 79 100%i 80 80 61 100%i
Invasive mechanical ventilation 18 46 10 20 0 38
Vasopressor support 76 83 62 48 25 25
Coronary artery abnormalities 24 36 9 8 21 N/A
LV dysfunction 19 N/A 52 38 39 N/A
Acute kidney injury 70 N/A 10 5 21 N/A
RRT N/A 1 N/A N/A N/A 0
ECMO N/A 4 4 4 0 2
Death 0 3 2 2 0 4

iStudy contained only patients admitted to pediatric ICUs.

Disposition

  • Admission
  • Varied reports on proportion requiring ICU level of care (21-80)1,4


See Also

COVID-19

External Links


References

  1. Capone CA et al. Characteristics, cardiac involvement, and outcomes of multisystem inflammatory disease of childhood (MIS-C) associated with SARS-CoV-2 infection. J Pediatr. 2020. (Epub ahead of print).
  2. Chiotos K et al. Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series. J Pediatric Infect Dis Soc. 2020;9(3):393-398.
  3. Davies P et al. Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicenter observational study. doi: 10.1016/S2352-4642(20)30215-7
  4. Dufort EM et al. Multisystem Inflammatory Syndrome in Children in New York State. N Eng J Med. 2020;383(4):347-358.
  5. Feldstein LR et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Eng J Med. 2020;383(4):334-346.
  6. Hoang et al. COVID-19 in 7780 pediatric patients: A systemic review. EClinicalMedicine. 2020;24. Accessed August 1, 2020. DOI: https://doi.org/10.1016/j.eclinm.2020.100433
  7. Levin M. Childhood Multisystem Inflammatory Syndrome – A New Challenge in the Pandemic. N Eng J Med. 2020;383(4):393-395.
  8. Lee PY et al. Distinct clinical and immunological features of SARS-COV-2-induced multisystem inflammatory syndrome in children. J Clin Invest. 2020. https://doi.org/10.1172/JCI141113
  9. Miller J et al. Gastrointestinal symptoms as a major presentation component of a novel multisystem inflammatory syndrome in children (MIS-C) that is related to COVID-19: a single center experience of 44 cases. Gastroenterology. 2020. (Epub ahead of print). doi: 10.1053/j.gastro.2020.05.079
  10. Rowley A. Understanding SARS-CoV-2 related multisystem inflammatory syndrome in children. Nat Rev Immunol. 2020;20(453-454). https://doi.org/10.1038/s41577-020-0367-5
  11. Shekerdemian LS et al. Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. 2020. doi:10.1001/jamapediatrics.2020.1948
  12. Verdoni L 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: 1771-8.
  13. Center for Disease Control and Prevention. Health Alert Network (HAN). Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). Accessed July 2020. https://emergency.cdc.gov/han/2020/han00432.asp
  14. https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19

 

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