Skip to main content
SpringerLink
Log in

Diagnostic and Therapeutic Approach to Multisystem Inflammatory Syndrome and Similar Condition

  • Published:
Biology Bulletin Reviews Aims and scope Submit manuscript

Abstract—

Multisystem inflammatory syndrome in children (MIS-C) can occur in kids, who have severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Clinically, characteristics of MIS-C are manifested by two or more involved organ systems, fever, severe illness, laboratory-evidenced inflammation, and laboratory or epidemiologically evidenced infection with SARS-CoV-2. MIS-C has several traits with Kawasaki illness, subsequent hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and toxic shock syndrome. The association between MIS-C and infection with SARS-CoV-2 shows the cause of post-infectious immunological dysregulation. Given the likelihood of rapid clinical deterioration, it is recommended to handle MIS-C patients in a pediatric critical care unit. Depending on the clinical presentation, a certain immunomodulatory therapy is advised. More research is needed to determine the connection between MIS-C and the immunological reaction to SARS-CoV-2 vaccines that are currently being developed. Numerous therapeutic methods have been developed for the treatment of COVID-19-associated MIS in children (MIS-C), the full elucidation of its etiology requires further studies. Here, we carefully review and summarize the previously released management guidance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Belot, A., Antona, D., Renolleau, S., et al., SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May, Eurosurveillance, 2020, vol. 25, p. 2001010.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Burnham, J.P. and Kollef, M.H., Understanding toxic shock syndrome, Intensive Care Med., 2015, vol. 41, pp. 1707–1710.

    Article  PubMed  Google Scholar 

  3. Burns, J.C. and Franco, A., The immunomodulatory effects of intravenous immunoglobulin therapy in Kawasaki disease, Expert Rev. Clin. Immunol., 2015, vol. 11, pp. 819–825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Burns, J.C., Mason, W.H., Glode, M.P., et al., Clinical and epidemiologic characteristics of patients referred for evaluation of possible Kawasaki disease, J. Pediatr., 1991, vol. 118, pp. 680–686.

    Article  CAS  PubMed  Google Scholar 

  5. Burns, J.C., Kushner, H.I., Bastian, J.F., et al., Kawasaki disease: A brief history, Pediatrics, 2000, vol. 106, no. 2, p. E27.

    Article  CAS  PubMed  Google Scholar 

  6. Carter, M.J., Fish, M., Jennings, A., et al., Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection, Nat. Med., 2020, vol. 26, pp. 1701–1707.

    Article  CAS  PubMed  Google Scholar 

  7. Choi, N.H., Fremed, M., Starc, T., et al., MIS-C and cardiac conduction abnormalities, Pediatrics, 2020, vol. 146, no. 6, p. e2020009738.

    Article  PubMed  Google Scholar 

  8. Cirks, B.T., Rowe, S.J., Jiang, S.Y., et al., Sixteen weeks later: Expanding the risk period for multisystem inflammatory syndrome in children, J. Pediatr. Infect. Dis. Soc., 2021, vol. 10, pp. 686–690.

    Article  CAS  Google Scholar 

  9. Davies, P., Evans, C., Kanthimathinathan, H.K., et al., Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: A multicentre observational study, Lancet Child Adolesc. Health, 2020, vol. 4, pp. 669–677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dolhnikoff, M., Ferranti, J.F., de Almeida Monteiro, R.A., et al., SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome, Lancet Child Adolesc. Health, 2020, vol. 4, no. 10, pp. 790–794.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Domico, M., McCanta, A.C., Hunt, J.L., et al., High-grade heart block requiring transvenous pacing associated with multisystem inflammatory syndrome in children during the COVID-19 pandemic, HeartRhythm Case Rep., 2020, vol. 6, pp. 811–814.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dufort, E.M., Koumans, E.H., Chow, E.J., et al., Multisystem inflammatory syndrome in children in New York State, N. Engl. J. Med., 2020, vol. 383, pp. 347–358.

    Article  CAS  PubMed  Google Scholar 

  13. Eleftheriou, D., Levin, M., Shingadia, D., et al., Management of Kawasaki disease, Arch. Dis. Child., 2014, vol. 99, pp. 74–83.

    Article  CAS  PubMed  Google Scholar 

  14. Espitia, C., Cervera, I., González, R., and Mancilla, R., A 38-kD Mycobacterium tuberculosis antigen associated with infection. Its isolation and serologic evaluation, Clin. Exp. Immunol., 1989, vol. 77, pp. 373–377.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Feldstein, L.R., Rose, E.B., Horwitz, S.M., et al., Multisystem inflammatory syndrome in US children and adolescents, N. Engl. J. Med., 2020, vol. 383, pp. 334–346.

    Article  CAS  PubMed  Google Scholar 

  16. Feldstein, L.R., Tenforde, M.W., Friedman, K.G., et al., Characteristics and outcomes of US children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19, JAMA, 2021, vol. 325, pp. 1074–1087.

    Article  CAS  PubMed  Google Scholar 

  17. Gamez-Gonzalez, L.B., Moribe-Quintero, I., Cisneros-Castolo, M., et al., Kawasaki disease shock syndrome: Unique and severe subtype of Kawasaki disease, Pediatr. Int., 2018, vol. 60, pp. 781–790.

    Article  CAS  PubMed  Google Scholar 

  18. Gatterre, P., Oualha, M., Dupic, L., et al., Kawasaki disease: An unexpected etiology of shock and multiple organ dysfunction syndrome, Intensive Care Med., 2012, vol. 38, pp. 872–878.

    Article  PubMed  Google Scholar 

  19. Godfred-Cato, S., Bryant, B., Leung, J., et al., COVID-19-associated multisystem inflammatory syndrome in children, United States, March-July, 2020, Morb. Mortal. Wkly Rep., 2020, vol. 69, no. 32, pp. 1074–1080.

    Article  CAS  Google Scholar 

  20. Guidance: Paediatric Multisystem Inflammatory Syndrome Temporally Associated with COVID-19, London: Royal College of Paediatrics and Child Health, 2020.

  21. Hajjeh, R.A., Reingold, A., Weil, A., et al., Toxic shock syndrome in the United States: Surveillance update, 1979–1996, Emerging Infect. Dis., 1999, vol. 5, no. 6, pp. 807–810.

    Article  CAS  Google Scholar 

  22. Hanson, K.E., Caliendo, A.M., Arias, C.A., et al., Infectious Diseases Society of America guidelines on the diagnosis of COVID-19, Clin. Infect. Dis., 2020, p. ciaa760.

  23. Henter, J.-I., Horne, A., Aricó, M., et al., HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis, Pediatr. Blood Cancer, 2007, vol. 48, pp. 124–131.

    Article  PubMed  Google Scholar 

  24. Jiang, L., Tang, K., Levin, M., et al., COVID-19 and multisystem inflammatory syndrome in children and adolescents, Lancet Infect. Dis., 2020, vol. 20, pp. e276–e288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kanegaye, J.T., Wilder, M.S., Molkara, D., et al., Recognition of a Kawasaki disease shock syndrome, Pediatrics, 2009, vol. 123, no. 5, pp. e783–e789.

    Article  PubMed  Google Scholar 

  26. Lee, P.Y., Day-Lewis, M., Henderson, L.A., et al., Distinct clinical and immunological features of SARS–CoV-2–induced multisystem inflammatory syndrome in children, J. Clin. Invest., 2020, vol. 130, pp. 5942–5950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. McCrindle, B.W., Rowley, A.H., Newburger, J.W., et al., Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association, Circulation, 2017, vol. 135, no. 17, pp. e927–e999.

    Article  PubMed  Google Scholar 

  28. Molloy, E.J., Nakra, N., Gale, C., et al., Multisystem inflammatory syndrome in children (MIS-C) and neonates (MIS-N) associated with COVID-19: Optimizing definition and management, Pediatr. Res., 2023, vol. 93, no. 6, pp. 1499–1508.

  29. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19), Centers for Disease Control and Prevention, 2020.

  30. Nakra, N.A., Blumberg, D.A., Herrera-Guerra, A., and Lakshminrusimha, S., Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: Review of clinical presentation, hypothetical pathogenesis, and proposed management, Children, 2020, vol. 7, p. 69.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Nasrabadi, T., Ruegner, H., Sirdari, Z.Z., et al., Using total suspended solids (TSS) and turbidity as proxies for evaluation of metal transport in river water, Appl. Geochem., 2016, vol. 68, pp. 1–9.

    Article  CAS  Google Scholar 

  32. Newburger, J.W., Takahashi, M., Gerber, M.A., et al., Diagnosis, treatment, and long-term management of Kawasaki disease: A statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association, Circulation, 2004, vol. 110, pp. 2747–2771.

    Article  PubMed  Google Scholar 

  33. Pang, J., Boshier, F.A., Alders, N., et al., SARS-CoV-2 polymorphisms and multisystem inflammatory syndrome in children, Pediatrics, 2020, p. 146.

  34. Parthasarathy, P., Agarwal, A., Chawla, K., et al., Upcoming biomarkers for the diagnosis of Kawasaki disease: A review, Clin. Biochem., 2015, vol. 48, pp. 1188–1194.

    Article  CAS  PubMed  Google Scholar 

  35. Radia, T., Williams, N., Agrawal, P., et al., Multi-system inflammatory syndrome in children, adolescents (MIS-C): A systematic review of clinical features and presentation, Paediatr. Respir. Rev., 2021, vol. 38, pp. 51–57.

    PubMed  Google Scholar 

  36. Riphagen, S., Gomez, X., Gonzalez-Martinez, C., et al., Hyperinflammatory shock in children during COVID-19 pandemic, Lancet, 2020, vol. 395, pp. 1607–1608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rosenberg, J., Gokaldas, R., and Gualberto, G., Hemophagocytic lymphohistiocytosis (HLH)/macrophage activated syndrome (MAS) with CNS Aspergillus, Neurology, 2017, vol. 88, p. P2.372.

  38. Shulman, S.T., Pediatric Coronavirus disease-2019—Associated multisystem inflammatory syndrome, J. Pediatr. Infect. Dis. Soc., 2020, vol. 9, no. 3, pp. 285–286.

  39. Singh, S., Jindal, A.K., and Pilania, R.K., Diagnosis of Kawasaki disease, Int. J. Rheum. Dis., 2018, vol. 21, pp. 36–44.

    Article  PubMed  Google Scholar 

  40. Son, M.B.F. and Friedman, K., COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis, UpToDate, Waltham, 2021. Accessed August 19, 2021.

  41. Son, M.B.F., Friedman, K., Kaplan, S.L., et al., COVID-19: multisystem inflammatory syndrome in children (MIS-C) management and outcome, UpToDate, 2021.

  42. Sperotto, F., Friedman, K.G., Son, M.B.F., 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, vol. 180, pp. 307–322.

    Article  CAS  PubMed  Google Scholar 

  43. Talkington, D.F., Schwartz, B., Black, C.M., et al., Association of phenotypic and genotypic characteristics of invasive Streptococcus pyogenes isolates with clinical components of streptococcal toxic shock syndrome, Infect. Immun., 1993, vol. 61, pp. 3369–3374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Terpos, E., Gavriatopoulou, M., Ntanasis-Stathopoulos, I., et al., The neutralizing antibody response post COVID-19 vaccination in patients with myeloma is highly dependent on the type of anti-myeloma treatment, Blood Cancer J., 2021, vol. 11, p. 138.

  45. Whittaker, E., Bamford, A., Kenny, J., et al., Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2, JAMA, 2020, vol. 324, pp. 259–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wu, C.M.Y. and Noska, A., Intrauterine device infection causing concomitant streptococcal toxic shock syndrome and pelvic abscess with Actinomyces odontolyticus bacteraemia, BMJ Case Rep., 2016, p. bcr2015213236.

Download references

ACKNOWLEDGMENTS

The authors would like to thank the University of Medical Sciences for their support.

Author information

Authors and Affiliations

  1. Hamadan University of Medical Sciences, Hamadan, Iran

    A. Emami

  2. Neurosurgery Research Group, Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran

    S. A. Yeganeh & T. Shahbazi

  3. Student Research Committee, Hamadan University of Medical Sciences School of Medicine, Hamadan, Iran

    H. A. Mohammadi

Authors
  1. A. Emami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. A. Yeganeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. A. Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. Shahbazi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Shahbazi.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARTS

Conflict of interest. The authors declare that they have no conflicts of interest.

Statement of the welfare of humans or animals. The article does not contain any studies involving humans or animals in experiments performed by any of the authors.

AUTHORS’ CONTRIBUTIONS

Afsaneh Emami and Taha Shahbazi devised the main conceptual ideas. Soheil Abdollahi Yeganeh wrote the initial draft of the manuscript. Hossein Ali Mohammadi and Taha Shahbazi prepared the figure. All authers reviewed the manuscript and edited it critically for important intellectual content. Taha Shahbazi supervised the study. All of the authors have read and agreed to the published version of the manuscript.

AVAILABILITY OF DATA AND MATERIAL

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Emami, A., Yeganeh, S.A., Mohammadi, H.A. et al. Diagnostic and Therapeutic Approach to Multisystem Inflammatory Syndrome and Similar Condition. Biol Bull Rev 13, 301–309 (2023). https://doi.org/10.1134/S2079086423040035

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S2079086423040035

Keywords:

Search

Navigation