RSS-Feed abonnieren
DOI: 10.1055/a-1715-5027
Das Pädiatrische Inflammatorische Multisystem Syndrom (PIMS) in der COVID-19 Pandemie
Paediatric Inflammatory Multisystem Syndrome (PIMS) in the COVID-19 Pandemic
Zusammenfassung
Nach einer meist mild verlaufenden SARS-CoV-2-Infektion kommt es bei einem kleinen Teil der Kinder nach einem Zeitraum von ca. 6–8 Wochen zu einer ausgeprägten multisystemischen Hyperinflammation (Pediatriac multisystemic inflammatory syndrome (PIMS)). Klinisch präsentieren sich diese Patienten mit Zeichen eines Kawasaki-Syndroms bzw. eines toxischen Schocksyndroms. Gerade die kardiale Manifestation mit einer deutlichen Einschränkung der Herzfunktion erfordert in vielen Fällen eine intensivmedizinische Behandlung.
Die Pathophysiologie ist trotz des beeindruckenden Erkenntnisgewinns der letzten 1 ½ Jahre noch unklar. Möglicherweise spielen Superantigene eine wesentliche Rolle, die T-Zellen an einer bestimmten β-Kette des T-Zellrezeptors polyklonal stimulieren.
Neben den z.T. intensivmedizinischen supportiven Maßnahmen werden zur Kontrolle der Inflammation intravenöse Immunglobuline, Steroide und Biologika eingesetzt.
Abstract
Following a SARS-CoV-2 infection, usually mild, a small proportion of children develop multisystemic hyperinflammation (paediatric inflammatory multisystem syndrome (PIMS)) within approximately 6–8 weeks. Clinically, these patients present with signs of Kawasaki syndrome or toxic shock syndrome. The cardiac manifestation, in particular, with a marked limitation of cardiac function, requires intensive medical treatment in many individuals.
The pathophysiology is still unclear although tremendous knowledge has been gained over the past one and a half years. A key role may be played by superantigens which, by binding to a specific β-chain of T-cell receptors, lead to polyclonal stimulation of T cells.
In addition to intensive care management, intravenous immunoglobulins, steroids, and biologics are used to control inflammation.
Publikationsverlauf
Artikel online veröffentlicht:
07. April 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart,
Germany
-
Literatur
- 1 Riphagen S, Gomez X, Gonzalez-Martinez C. et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020; 395: 1607-1608
- 2 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: 1771-1778
- 3 Sorg A.L., H. M., Doenhardt M., Diffloth H., Schroten H., v. Kries R., Berner R., Armann J. Risk of Hospitalization, severe disease, and mortality due to COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany. https://www.medrxiv.org/content/10.1101/2021.11.30.21267048v1 (2021).
- 4 Loomba RS, Villarreal EG, Flores S. COVID-19 and Hyperinflammatory Syndrome in Children: Kawasaki Disease with Macrophage Activation Syndrome in Disguise?. Cureus 2020; 12: e9515
- 5 Abrams JY. et al. Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study. Lancet Child Adolesc Health 2021; 5: 323-331
- 6 Whittaker E. et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA 2020; 324: 259-269
- 7 Hoste L, Van Paemel R, Haerynck F. Multisystem inflammatory syndrome in children related to COVID-19: a systematic review. Eur J Pediatr 2021; 180: 2019-2034
- 8 WHO https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19
- 9 CDC https://emergency.cdc.gov/han/2020/han00432.asp
- 10 RCPCH https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf
- 11 Kaushik S. et al. Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Infection (MIS-C): A Multi-institutional Study from New York City. J Pediatr 2020; 224: 24-29
- 12 Yasuhara J, Watanabe K, Takagi H. et al. COVID-19 and multisystem inflammatory syndrome in children: A systematic review and meta-analysis. Pediatr Pulmonol 2021; 56: 837-848
- 13 Bastug A. et al. Multiple system inflammatory syndrome associated with SARS-CoV-2 infection in an adult and an adolescent. Rheumatol Int 2021; 41: 993-1008
- 14 Piekarski F, Steinbicker AU, Armann JP. The multisystem inflammatory syndrome in children and its association to SARS-CoV-2. Curr Opin Anaesthesiol 2021; 34: 521-529
- 15 Brumfiel CM, DiLorenzo AM, Petronic-Rosic VM. Dermatologic manifestations of COVID-19-associated multisystem inflammatory syndrome in children. Clin Dermatol 2021; 39: 329-333
- 16 Zhou C. et al. Laboratory parameters between multisystem inflammatory syndrome in children and Kawasaki disease. Pediatr Pulmonol 2021; 56: 3688-3698
- 17 Zhao Y, Patel J, Huang Y. et al. Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis. Am J Emerg Med 2021; 49: 62-70
- 18 Belot A, Levy-Bruhl D. French Covid-19 Pediatric Inflammation, C. Multisystem Inflammatory Syndrome in Children in the United States. N Engl J Med 2020; 383: 1793-1794
- 19 Belot A. et al. SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020. Euro Surveill 2020; 25
- 20 Dufort EM. et al. Multisystem Inflammatory Syndrome in Children in New York State. N Engl J Med 2020; 383: 347-358
- 21 Feldstein LR. et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med 2020; 383: 334-346
- 22 Toubiana J. et al. Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case-control study, Paris, France, April to May 2020. Euro Surveill 2020; 25
- 23 Ahmed M. et al. Multisystem inflammatory syndrome in children: A systematic review. EClinicalMedicine 2020; 26: 100527
- 24 Sancho-Shimizu V. et al. SARS-CoV-2-related MIS-C: A key to the viral and genetic causes of Kawasaki disease?. J Exp Med 2021; 218
- 25 Zhang Q. et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 2020; 370
- 26 Chou J. et al. Mechanisms underlying genetic susceptibility to multisystem inflammatory syndrome in children (MIS-C). J Allergy Clin Immunol 2021; 148: 732-738 e731
- 27 de Cevins C. et al. A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis. Med (N Y) 2021; 2: 1072-1092 e1077
- 28 Peart Akindele N. et al. Distinct Cytokine and Chemokine Dysregulation in Hospitalized Children With Acute Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome With Similar Levels of Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 Shedding. J Infect Dis 2021; 224: 606-615
- 29 Carter MJ. et al. Peripheral immunophenotypes in children with multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Nat Med 2020; 26: 1701-1707
- 30 Diorio C. et al. Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS-CoV-2. J Clin Invest 2020; 130: 5967-5975
- 31 Gruber CN. et al. Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C). Cell 2020; 183: 982-995 e914
- 32 Vella LA. et al. Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19. Sci Immunol 2021; 6
- 33 Toubiana J. et al. Distinctive Features of Kawasaki Disease Following SARS-CoV-2 Infection: a Controlled Study in Paris, France. J Clin Immunol 2021; 41: 526-535
- 34 Porritt RA. et al. The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children. J Clin Invest 2021;
- 35 Bartsch YC. et al. Humoral signatures of protective and pathological SARS-CoV-2 infection in children. Nat Med 2021; 27: 454-462
- 36 Yonker LM. et al. Pediatric Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Clinical Presentation, Infectivity, and Immune Responses. J Pediatr 2020; 227: 45-52 e45
- 37 Anderson EM. et al. Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) Antibody Responses in Children With Multisystem Inflammatory Syndrome in Children (MIS-C) and Mild and Severe Coronavirus Disease 2019 (COVID-19). J Pediatric Infect Dis Soc 2021; 10: 669-673
- 38 Ramaswamy A. et al. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021; 54: 1083-1095 e1087
- 39 Beckmann ND. et al. Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children. Nat Commun 2021; 12: 4854
- 40 Uzhachenko RV, Shanker A. CD8(+) T Lymphocyte and NK Cell Network: Circuitry in the Cytotoxic Domain of Immunity. Front Immunol 2019; 10: 1906
- 41 Krakauer T. Staphylococcal Superantigens: Pyrogenic Toxins Induce Toxic Shock. Toxins (Basel) 2019; 11
- 42 Cheng MH. et al. Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation. Proc Natl Acad Sci U S A 2020; 117: 25254-25262
- 43 Porritt RA. et al. HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children. J Clin Invest 2021; 131
- 44 Moreews M. et al. Polyclonal expansion of TCR Vbeta 21.3(+) CD4(+) and CD8(+) T cells is a hallmark of Multisystem Inflammatory Syndrome in Children. Sci Immunol 2021; 6
- 45 Tanaka Y. et al. Emerging Role of Fractalkine in the Treatment of Rheumatic Diseases. Immunotargets Ther 2020; 9: 241-253
- 46 Esteve-Sole A. et al. Similarities and differences between the immunopathogenesis of COVID-19-related pediatric multisystem inflammatory syndrome and Kawasaki disease. J Clin Invest 2021; 131
- 47 Guo T. et al. A Subset of Human Autoreactive CD1c-Restricted T Cells Preferentially Expresses TRBV4-1(+) TCRs. J Immunol 2018; 200: 500-511
- 48 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 multicentre observational study. Lancet Child Adolesc Health 2020; 4: 669-677
- 49 Cheung EW. et al. Multisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City. JAMA 2020; 324: 294-296
- 50 Belhadjer Z. et al. Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic. Circulation 2020; 142: 429-436
- 51 Ouldali N. et al. Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children. JAMA 2021; 325: 855-864
- 52 McArdle AJ. et al. Treatment of Multisystem Inflammatory Syndrome in Children. N Engl J Med 2021; 385: 11-22
- 53 Son MBF. et al. Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes. N Engl J Med 2021; 385: 23-34
- 54 Belhadjer Z. et al. Addition of Corticosteroids to Immunoglobulins Is Associated With Recovery of Cardiac Function in Multi-Inflammatory Syndrome in Children. Circulation 2020; 142: 2282-2284
- 55 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: e340-e346
- 56 Ter Haar NM. et al. Treatment to Target Using Recombinant Interleukin-1 Receptor Antagonist as First-Line Monotherapy in New-Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five-Year Follow-Up Study. Arthritis Rheumatol 2019; 71: 1163-1173
- 57 Abdel-Haq N. et al. SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment. Eur J Pediatr 2021; 180: 1581-1591
- 58 Radia T. et al. Multi-system inflammatory syndrome in children & adolescents (MIS-C): A systematic review of clinical features and presentation. Paediatr Respir Rev 2021; 38: 51-57
- 59 Cole LD. et al. IVIG Compared to IVIG Plus Infliximab in Multisystem Inflammatory Syndrome in Children. Pediatrics 2021;
- 60 Whitworth H. et al. Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C. Blood 2021; 138: 190-198
- 61 Schlapbach LJ. et al. Best Practice Recommendations for the Diagnosis and Management of Children With Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS; Multisystem Inflammatory Syndrome in Children, MIS-C) in Switzerland. Front Pediatr 2021; 9: 667507