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Erschienen in: Current Allergy and Asthma Reports 5/2022

22.03.2022 | COVID-19 | Pediatric Allergy and Immunology (WK Dolen, Section Editor) Zur Zeit gratis

Multisystem Inflammatory Syndrome in Children (MIS-C)

verfasst von: Julisa M. Patel

Erschienen in: Current Allergy and Asthma Reports | Ausgabe 5/2022

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Abstract

Purpose of Review

The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed into a pandemic. A unique challenge of this pandemic has been the emergence of multisystem inflammatory syndrome in children (MIS-C), a rare post-infectious hyperinflammatory disorder associated with SARS-CoV-2. This syndrome is characterized by overwhelming systemic inflammation, fever, hypotension, and cardiac dysfunction. This disorder may also have features overlapping with Kawasaki disease (KD), macrophage activation syndrome (MAS), and toxic shock syndrome (TSS). The goal of this review is to outline the presenting features, presumed immunopathogenesis, management, and outcomes of patients with MIS-C.

Recent Findings

Patients with MIS-C present with characteristics that fall within a wide clinical spectrum. Main features include fever, gastrointestinal symptoms such as abdominal pain and diarrhea, and cardiac complications such as myocarditis and coronary artery aneurysms, although various other features have been reported. Younger children may present with features of Kawasaki-like disease, and older children are often admitted to the intensive care unit with cardiogenic shock. Current treatment guidelines recommend intravenous immunoglobulins (IVIG) and glucocorticoids, with utilization of biologics in refractory cases. Fortunately, the majority of patients recover, with resolution of the systemic inflammation and cardiac abnormalities. Mortality from MIS-C is rare.

Summary

This review provides an overview of the presenting features, proposed pathogenesis, suggested therapies, and outcomes of MIS-C. Clinicians must have a high clinical suspicion for this disorder in children who have had recent COVID-19 infection or exposure and present with a significant inflammatory response. Understanding of this disorder continues to evolve, and prompt diagnosis and treatment allow for the best possible outcome for patients with MIS-C.
Literatur
2.
Zurück zum Zitat Kaushik A, Gupta S, Sood M, Sharma S, Verma S. A systematic review of multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection. Pediatr Infect Dis J. 2020;39(11):e340–6. CrossRefPubMed Kaushik A, Gupta S, Sood M, Sharma S, Verma S. A systematic review of multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection. Pediatr Infect Dis J. 2020;39(11):e340–6. CrossRefPubMed
4.
Zurück zum Zitat Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, Wu C, Liu H, Liu D, Shao J, Peng X, Yang Y, Liu Z, Xiang Y, Zhang F, Silva RM, Pinkerton KE, Shen K, Xiao H, Xu S, Wong GWK; Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 infection in children. N Engl J Med. 2020;382(17):1663–1665.  https://​doi.​org/​10.​1056/​NEJMc2005073. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, Zhang W, Wang Y, Bao S, Li Y, Wu C, Liu H, Liu D, Shao J, Peng X, Yang Y, Liu Z, Xiang Y, Zhang F, Silva RM, Pinkerton KE, Shen K, Xiao H, Xu S, Wong GWK; Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 infection in children. N Engl J Med. 2020;382(17):1663–1665.  https://​doi.​org/​10.​1056/​NEJMc2005073.
6.
Zurück zum Zitat • Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020; 395(10237):1607–1608. https://​doi.​org/​10.​1016/​S0140-6736(20)31094-1. Early report describing a hyperinflammatory illness affecting children during the early part of the pandemic, later named MIS-C. • Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020; 395(10237):1607–1608. https://​doi.​org/​10.​1016/​S0140-6736(20)31094-1. Early report describing a hyperinflammatory illness affecting children during the early part of the pandemic, later named MIS-C.
7.
Zurück zum Zitat • 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. https://​doi.​org/​10.​1016/​S0140-6736(20)31103-X. One of the earliest reports of an increased number of Kawasaki-like disease cases during the early part of the pandemic. • 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. https://​doi.​org/​10.​1016/​S0140-6736(20)31103-X. One of the earliest reports of an increased number of Kawasaki-like disease cases during the early part of the pandemic.
8.
Zurück zum Zitat McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E; 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; and 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. Circulation. 2017;135(17):e927–e999. https://​doi.​org/​10.​1161/​CIR.​0000000000000484​. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, Baker AL, Jackson MA, Takahashi M, Shah PB, Kobayashi T, Wu MH, Saji TT, Pahl E; 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; and 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. Circulation. 2017;135(17):e927–e999. https://​doi.​org/​10.​1161/​CIR.​0000000000000484​.
9.
Zurück zum Zitat Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383(4):334–346. Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383(4):334–346.
10.
Zurück zum Zitat Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. 2020;383(4):347–358. Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. 2020;383(4):347–358.
14.
Zurück zum Zitat Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC, Herberg J, Bajolle F, Randanne PC, Salas-Mera D, Foldvari S, Chowdhury D, Munoz R, Bianco F, Singh Y, Levin M, Bonnet D, Fraisse A. Multisystem inflammatory syndrome in children: an international survey. Pediatrics. 2021;147(2):e2020024554. https://​doi.​org/​10.​1542/​peds.​2020-024554. Epub 2020 Nov 24. PMID: 33234669. Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC, Herberg J, Bajolle F, Randanne PC, Salas-Mera D, Foldvari S, Chowdhury D, Munoz R, Bianco F, Singh Y, Levin M, Bonnet D, Fraisse A. Multisystem inflammatory syndrome in children: an international survey. Pediatrics. 2021;147(2):e2020024554. https://​doi.​org/​10.​1542/​peds.​2020-024554. Epub 2020 Nov 24. PMID: 33234669.
17.
Zurück zum Zitat Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, Tan Z, Zicari S, Ruggiero A, Pascucci GR, Santilli V, Campbell T, Bryceson Y, Eriksson D, Wang J, Marchesi A, Lakshmikanth T, Campana A, Villani A, Rossi P; CACTUS Study Team, Landegren N, Palma P, Brodin P. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183(4):968–981.e7. https://​doi.​org/​10.​1016/​j.​cell.​2020.​09.​016. Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, Tan Z, Zicari S, Ruggiero A, Pascucci GR, Santilli V, Campbell T, Bryceson Y, Eriksson D, Wang J, Marchesi A, Lakshmikanth T, Campana A, Villani A, Rossi P; CACTUS Study Team, Landegren N, Palma P, Brodin P. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183(4):968–981.e7. https://​doi.​org/​10.​1016/​j.​cell.​2020.​09.​016.
23.
Zurück zum Zitat Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, et al. 2016 classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol. 2016;68(3):566–76. https://​doi.​org/​10.​1002/​art.​39332. CrossRefPubMed Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, et al. 2016 classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol. 2016;68(3):566–76. https://​doi.​org/​10.​1002/​art.​39332. CrossRefPubMed
24.
Zurück zum Zitat • Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiri H, Behrens EM, Ferris A, Kernan KF, Schulert GS, Seo P, Son MBF, Tremoulet AH, Yeung RSM, Mudano AS, Turner AS, Karp DR, Mehta JJ. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 3. Arthritis Rheumatol. 2022 Feb 3. https://​doi.​org/​10.​1002/​art.​42062. Epub ahead of print. Outlines clinical practice guidelines for the evaluation and management of patients with suspected or diagnosed MIS-C. • Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiri H, Behrens EM, Ferris A, Kernan KF, Schulert GS, Seo P, Son MBF, Tremoulet AH, Yeung RSM, Mudano AS, Turner AS, Karp DR, Mehta JJ. American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 3. Arthritis Rheumatol. 2022 Feb 3. https://​doi.​org/​10.​1002/​art.​42062. Epub ahead of print. Outlines clinical practice guidelines for the evaluation and management of patients with suspected or diagnosed MIS-C.
25.
Zurück zum Zitat Ouldali N, Toubiana J, Antona D, Javouhey E, Madhi F, Lorrot M, Léger PL, Galeotti C, Claude C, Wiedemann A, Lachaume N, Ovaert C, Dumortier M, Kahn JE, Mandelcwajg A, Percheron L, Biot B, Bordet J, Girardin ML, Yang DD, Grimaud M, Oualha M, Allali S, Bajolle F, Beyler C, Meinzer U, Levy M, Paulet AM, Levy C, Cohen R, Belot A, Angoulvant F; 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. JAMA. 2021;325(9):855–864. https://​doi.​org/​10.​1001/​jama.​2021.​0694. Ouldali N, Toubiana J, Antona D, Javouhey E, Madhi F, Lorrot M, Léger PL, Galeotti C, Claude C, Wiedemann A, Lachaume N, Ovaert C, Dumortier M, Kahn JE, Mandelcwajg A, Percheron L, Biot B, Bordet J, Girardin ML, Yang DD, Grimaud M, Oualha M, Allali S, Bajolle F, Beyler C, Meinzer U, Levy M, Paulet AM, Levy C, Cohen R, Belot A, Angoulvant F; 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. JAMA. 2021;325(9):855–864. https://​doi.​org/​10.​1001/​jama.​2021.​0694.
27.
Zurück zum Zitat Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, Oltolini C, Castiglioni B, Tassan Din C, Boffini N, Tomelleri A, Farina N, Ruggeri A, Rovere-Querini P, Di Lucca G, Martinenghi S, Scotti R, Tresoldi M, Ciceri F, Landoni G, Zangrillo A, Scarpellini P, Dagna L. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2(6):e325–31. https://​doi.​org/​10.​1016/​S2665-9913(20)30127-2. CrossRefPubMedPubMedCentral Cavalli G, De Luca G, Campochiaro C, Della-Torre E, Ripa M, Canetti D, Oltolini C, Castiglioni B, Tassan Din C, Boffini N, Tomelleri A, Farina N, Ruggeri A, Rovere-Querini P, Di Lucca G, Martinenghi S, Scotti R, Tresoldi M, Ciceri F, Landoni G, Zangrillo A, Scarpellini P, Dagna L. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2(6):e325–31. https://​doi.​org/​10.​1016/​S2665-9913(20)30127-2. CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, Bruzzi P, Boni F, Braglia L, Turrà C, Ballerini PF, Sciascia R, Zammarchi L, Para O, Scotton PG, Inojosa WO, Ravagnani V, Salerno ND, Sainaghi PP, Brignone A, Codeluppi M, Teopompi E, Milesi M, Bertomoro P, Claudio N, Salio M, Falcone M, Cenderello G, Donghi L, Del Bono V, Colombelli PL, Angheben A, Passaro A, Secondo G, Pascale R, Piazza I, Facciolongo N, Costantini M; RCT-TCZ-COVID-19 Study Group. Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. JAMA Intern Med. 2021;181(1):24–31. https://​doi.​org/​10.​1001/​jamainternmed.​2020.​6615. Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, Bruzzi P, Boni F, Braglia L, Turrà C, Ballerini PF, Sciascia R, Zammarchi L, Para O, Scotton PG, Inojosa WO, Ravagnani V, Salerno ND, Sainaghi PP, Brignone A, Codeluppi M, Teopompi E, Milesi M, Bertomoro P, Claudio N, Salio M, Falcone M, Cenderello G, Donghi L, Del Bono V, Colombelli PL, Angheben A, Passaro A, Secondo G, Pascale R, Piazza I, Facciolongo N, Costantini M; RCT-TCZ-COVID-19 Study Group. Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. JAMA Intern Med. 2021;181(1):24–31. https://​doi.​org/​10.​1001/​jamainternmed.​2020.​6615.
30.
Zurück zum Zitat Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, Skiest D, Aziz MS, Cooper N, Douglas IS, Savic S, Youngstein T, Del Sorbo L, Cubillo Gracian A, De La Zerda DJ, Ustianowski A, Bao M, Dimonaco S, Graham E, Matharu B, Spotswood H, Tsai L, Malhotra A. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med. 2021;384(16):1503–16. https://​doi.​org/​10.​1056/​NEJMoa2028700. CrossRefPubMed Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, Skiest D, Aziz MS, Cooper N, Douglas IS, Savic S, Youngstein T, Del Sorbo L, Cubillo Gracian A, De La Zerda DJ, Ustianowski A, Bao M, Dimonaco S, Graham E, Matharu B, Spotswood H, Tsai L, Malhotra A. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med. 2021;384(16):1503–16. https://​doi.​org/​10.​1056/​NEJMoa2028700. CrossRefPubMed
Metadaten
Titel
Multisystem Inflammatory Syndrome in Children (MIS-C)
verfasst von
Julisa M. Patel
Publikationsdatum
22.03.2022
Verlag
Springer US
Schlagwort
COVID-19
Erschienen in
Current Allergy and Asthma Reports / Ausgabe 5/2022
Print ISSN: 1529-7322
Elektronische ISSN: 1534-6315
DOI
https://doi.org/10.1007/s11882-022-01031-4

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