View More View Less
  • 1 Semmelweis Egyetem, Általános Orvostudományi Kar, II. Gyermekgyógyászati Klinika, Budapest, Tűzoltó u. 7–9., 1094
  • | 2 Gottsegen György Országos Kardiológiai Intézet, Budapest
  • | 3 Semmelweis Egyetem, Általános Orvostudományi Kar, I. Gyermekgyógyászati Klinika, Budapest
  • | 4 Debreceni Egyetem, Általános Orvostudományi Kar, Gyermekgyógyászati Klinika, Debrecen
  • | 5 Pécsi Tudományegyetem, Általános Orvostudományi Kar, Gyermekgyógyászati Klinika, Pécs
  • | 6 Semmelweis Egyetem, Immunológiai Laboratórium, Budapest
  • | 7 Semmelweis Egyetem, Általános Orvostudományi Kar, Városmajori Szív- és Érgyógyászati Klinika, Budapest
  • | 8 Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház, Velkey László Gyermekegészségügyi Központ, Miskolc
  • | 9 University of Alabama, Department of Pediatrics, Birmingham, Alabama, USA
  • | 10 Debreceni Egyetem, Általános Orvostudományi Kar, Reumatológiai Tanszék, Debrecen
Open access

Összefoglaló. A SARS-CoV-2-fertőzés ritka gyermekkori szövődménye a sokszervi gyulladás, angol terminológiával paediatric inflammatory multisystem syndrome (PIMS). Két vagy több szerv érintettségével járó, súlyos tünetekkel induló betegségről van szó, amelynek tünetei átfedést mutatnak a Kawasaki-betegséggel, a toxikus sokk szindrómával és a makrofágaktivációs szindrómával. A PIMS-betegek intenzív terápiás osztályon vagy intenzív terápiás háttérrel rendelkező intézményben kezelendők, ahol biztosítottak a kardiológiai ellátás feltételei is. A szükséges immunterápia a klinikai prezentációtól függ. A jelen közleményben a szerzők a releváns nemzetközi irodalom áttekintését követően ajánlást tesznek a PIMS diagnosztikai és terápiás algoritmusára. Orv Hetil. 2021; 162(17): 652–667.

Summary. Pediatric inflammatory multisystem syndrome (PIMS) is a rare complication of SARS-CoV-2 infection in children. PIMS is a severe condition, involving two or more organ systems. The symptoms overlap with Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. PIMS patients should be treated in an intensive care unit or in an institution with an intensive care background, where cardiological care is also provided. The required specific immunotherapy depends on the clinical presentation. In this paper, after reviewing the relevant international literature, the authors make a recommendation for the diagnostic and therapeutic algorithm for PIMS. Orv Hetil. 2021; 162(17): 652–667.

  • 1

    Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS–CoV-2 and hyperinflammation in pediatric COVID-19. Version 1. Arthritis Rheumatol. 2020; 72: 1791–1805.

  • 2

    Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19. Version 2. Arthritis Rheumatol. 2020 Dec 5. . [Epub ahead of print]

    • Crossref
    • Export Citation
  • 3

    Harwood R, Allin B, Jones CE, et al. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process. Lancet Child Adolesc Health 2021; 5: 133–141. [Erratum: Lancet Child Adolesc Health 2021; 5: e5.]

  • 4

    Nijman RG, De Guchtenaere AD, Koletzko B, et al. Pediatric inflammatory multisystem syndrome: Statement by the Pediatric Section of the European Society for Emergency Medicine and European Academy of Pediatrics. Front Pediatr. 2020; 8: 490.

  • 5

    Kanegaye JT, Wilder MS, Molkara D, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics 2009; 123: e783–e789.

  • 6

    Dominguez SR, Friedman K, Seewald R, et al. Kawasaki disease in a pediatric intensive care unit: a case-control study. Pediatrics 2008; 122: e786–e790.

  • 7

    Ahmed M, Advani S, Moreira A, et al. Multisystem inflammatory syndrome in children: a systematic review. EClinicalMedicine 2020; 26: 100527.

  • 8

    Inciardi RM, Lupi L, Zaccone G, et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020; 5: 819–824.

  • 9

    Long B, Brady WJ, Koyfman A, et al. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020; 38: 1504–1507.

  • 10

    Belhadjer Z, Méot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation 2020; 142: 429–436.

  • 11

    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; 324: 259–269.

  • 12

    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; 69: 1074–1080.

  • 13

    Hoang A, Chorath K, Moreira A, et al. COVID-19 in 7780 pediatric patients: a systematic review. EClinicalMedicine 2020; 24: 100433.

  • 14

    Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the Covid-19 pandemic in Paris, France: prospective observational study. BMJ 2020; 369: m2094.

  • 15

    Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020; 383: 334–346.

  • 16

    Gruber CN, Patel RS, Trachtman R, et al. Mapping systemic inflammation and antibody responses in multisystem inflammatory syndrome in children (MIS-C). Cell 2020; 183: 982–995.e14.

  • 17

    Swann OV, Holden KA, Turtle L, et al. Clinical characteristics of children and young people admitted to hospital with Covid-19 in United Kingdom: prospective multicentre observational cohort study. BMJ 2020; 370: m3249.

  • 18

    Hanson KE, Caliendo AM, Arias CA, et al. Infectious Diseases Society of America guidelines on the diagnosis of COVID-19: serologic testing. Clin Infect Dis. 2020 Sep 12; ciaa1343. . [Epub ahead of print]

    • Crossref
    • Export Citation
  • 19

    Weisberg SP, Connors T, Zhu Y, et al. Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19. medRxiv 2020 Jul 14. Doi: 10.1101/2020.07.12.20151068.

  • 20

    Rostad CA, Chahroudi A, Mantus G, et al. Quantitative SARS-CoV-2 serology in children with multisystem inflammatory syndrome (MIS-C). Pediatrics 2020; 146: e2020018242.

  • 21

    Centers for Disease Control and Prevention. Options to reduce quarantine for contacts of persons with SARS-CoV-2 infection using symptom monitoring and diagnostic testing. CDC, Dec 2, 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-brief-options-to-reduce-quarantine.html [accessed: January 31, 2021].

  • 22

    Cheng HY, Jian SW, Liu DP, et al. Contact tracing assessment of COVID-19 transmission dynamics in Taiwan and risk at different exposure periods before and after symptom onset. JAMA Intern Med. 2020; 180: 1156–1163.

  • 23

    Kim MC, Cui C, Shin KR, et al. Duration of culturable SARS-CoV-2 in hospitalized patients with COVID-19. N Engl J Med. 2021; 384: 671–673.

  • 24

    Korea Centers for Disease Control and Prevention. Findings from investigation and analysis of re-positive cases. May 19, 2020. Available from: https://www.cdc.go.kr/board/board.es?mid=&bid=0030&act=view&list_no=367267& [accessed: January 31, 2021].

  • 25

    Li N, Wang X, Lv T. Prolonged SARS-CoV-2 RNA shedding: not a rare phenomenon. J Med Virol. 2020; 92: 2286–2287.

  • 26

    Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China. Pediatrics 2020; 145: e20200702.

  • 27

    Han MS, Choi EH, Chang SH, et al. Clinical characteristics and viral RNA detection in children with coronavirus disease 2019 in the Republic of Korea. JAMA Pediatr. 2021; 175: 73–80.

  • 28

    Denning DW, Kilcoyne A, Ucer C. Non-infectious status indicated by detectable IgG antibody to SARS-CoV-2. Br Dent J. 2020; 229: 521–524.

  • 29

    Iyer AS, Jones FK, Nodoushani A, et al. Dynamics and significance of the antibody response to SARS-CoV-2 infection. MedRxiv Prepr Serv Heal Sci. 2020 Jul 20. Doi: 10.1101/2020.07.18.20155374.

  • 30

    Melendez E, Whitney JE, Norton JS, et al. A pilot study of the association of amino-terminal pro-B-type natriuretic peptide and severity of illness in pediatric septic shock. Pediatr Crit Care Med. 2019; 20: e55–e60.

  • 31

    Lippi G, Salvagno GL, Guidi GC. Cardiac troponins in pediatric myocarditis. Pediatrics 2008; 121: 864.

  • 32

    Baker P, Leckie T, Harrington D, et al. Exercise-induced cardiac troponin elevation: an update on the evidence, mechanism and implications. Int J Cardiol Heart Vasc. 2019; 22: 181–186.

  • 33

    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; 135: e927–e999.

  • 34

    Capone CA, Subramony A, Sweberg T, et al. Characteristics, cardiac involvement, and outcomes of multisystem inflammatory syndrome of childhood (MIS-C) associated with SARS-CoV-2 infection. J Pediatrics 2020; 224: 141–145.

  • 35

    Tracewski P, Ludwikowska KM, Szenborn L, et al. The first case of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) in Poland, complicated by giant coronary artery aneurysms. Kardiol Pol. 2020; 78: 1064–1065.

  • 36

    Davies P, Evans C, Kanthimathinathan HK, 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.

  • 37

    Ramcharan T, Nolan O, Lai CY, et al. Paediatric inflammatory multisystem syndrome: temporally associated with SARS-CoV-2 (PIMS-TS): cardiac features, management and short-term outcomes at a UK tertiary paediatric hospital. Pediatr Cardiol. 2020; 41: 1391–1401.

  • 38

    Berg J, Kottwitz J, Baltensperger N, et al. Cardiac magnetic resonance imaging in myocarditis reveals persistent disease activity despite normalization of cardiac enzymes and inflammatory parameters at 3-month follow-up. Circ Heart Fail. 2018; 10: e004262.

  • 39

    Maron BJ, Udelson JE, Bonow RO, et al. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities. Task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis. Circulation 2015; 132: e273–e380.

  • 40

    Ripley DP, Musa TA, Dobson LE, et al. Cardiovascular magnetic resonance imaging: what the general cardiologist should know. Heart 2016; 102: 1589–1603.

  • 41

    Tschöpe C, Ammirati E, Bozkurt B, et al. Myocarditis and inflammatory cardiomyopathy: current evidence and future directions. Nat Rev Cardiol. 2021; 18: 169–193.

  • 42

    Grün S, Schumm J, Greulich S, et al. Long-term follow-up of biopsy-proven viral myocarditis predictors of mortality and incomplete recovery. J Am Coll Cardiol. 2012; 59: 1604–1615.

  • 43

    Banka P, Robinson JD, Uppu SC, et al. Cardiovascular magnetic resonance techniques and findings in children with myocarditis: a multicenter retrospective study. J Cardiovasc Magn Reson. 2015; 17: 96.

  • 44

    Kariyanna PT, Sutarjono B, Grewal E, et al. A systematic review of COVID-19 and myocarditis. Am J Med Case Rep. 2020; 8: 299–305.

  • 45

    Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020; 5: 1265–1273.

  • 46

    Vágó H, Szabó L, Dohy Z, et al. Cardiac magnetic resonance findings in patients recovered from COVID-19: initial experiences in elite athletes. JACC Cardiovasc Imaging 2020 Dec 16. . [Epub ahead of print]

    • Crossref
    • Export Citation
  • 47

    Halushka MK, Vander Heide RS. Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 postmortem examinations. Cardiovasc Pathol. 2021; 50: 107300.

  • 48

    Wilson MG, Hull JH, Rogers J, et al. Cardiorespiratory considerations for return-to-play in elite athletes after COVID-19 infection: a practical guide for sport and exercise medicine physicians. Br J Sport Med. 2020; 54: 1157–1161.

  • 49

    Ouldali N, Toubiana J, Antona D, 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.

  • 50

    Ameling S, Bhardwaj G, Hammer E, et al. Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution. Basic Res Cardiol. 2016; 111: 53.

  • 51

    Dandel M, Wallukat G, Englert A, et al. Long-term benefits of immunoadsorption in β1-adrenoceptor autoantibody-positive transplant candidates with dilated cardiomyopathy. Eur J Heart Fail. 2012; 14: 1374–1388.

  • 52

    Trimpert C, Herda LR, Eckerle LG, et al. Immunoadsorption in dilated cardiomyopathy: long-term reduction of cardiodepressant antibodies. Eur J Clin Invest. 2010; 40: 685–691.

  • 53

    Amabile N, Fraisse A, Bouvenot J, et al. Outcome of acute fulminant myocarditis in children. Heart 2006; 92: 1269–1273.

  • 54

    Wardle AJ, Connolly GM, Seager MJ, et al. Corticosteroids for the treatment of Kawasaki disease in children. Cochrane Database Syst Rev. 2017; 1: CD011188.

  • 55

    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: 1771–1778.

  • 56

    Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, et al. Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy. Circulation 2001; 104: 39–45.

  • 57

    Kraft L, Erdenesukh T, Sauter M, et al. Blocking the IL-1β signalling pathway prevents chronic viral myocarditis and cardiac remodeling. Basic Res Cardiol. 2019; 114: 11.

  • 58

    U. S. National Library of Medicine. RHAPSODY Phase 3 study to assess the efficacy and safety of rilonacept treatment in subjects with recurrent pericarditis. First posted: Nov 9, 2018. Available from: https://clinicaltrials.gov/ct2/show/NCT03737110 [accessed: January 30, 2021].

  • 59

    U. S. National Library of Medicine. Anakinra versus placebo for the treatment of acute myocarditis (ARAMIS). Last update: Dec 4, 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT03018834 [accessed: January 30, 2021].

  • 60

    Kone-Paut I, Cimaz R, Herberg J, et al. The use of interleukin 1 receptor antagonist (anakinra) in Kawasaki disease: a retrospective cases series. Autoimmun Rev. 2018; 17: 768–774.

  • 61

    Middeldorp S, Coppens M, van Haaps TF, et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020; 18: 1995–2002.

  • 62

    Wichmann D, Sperhake JP, Lütgehetmann M, et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med. 2020; 173: 268–277.

  • 63

    Tang N, Bai H, Chen X, et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020; 18: 1094–1099.

  • 64

    DeBiasi RL, Song X, Delaney M, et al. Severe COVID-19 in children and young adults in the Washington, DC Metropolitan Region. J Pediatr. 2020; 223: 199–203.e1.

  • 65

    Carpenter SL, Richardson T, Hall M. Increasing rate of pulmonary embolism diagnosed in hospitalized children in the United States from 2001 to 2014. Blood Adv. 2018; 2: 1403–1408.

  • 66

    Del Borrello G, Giraudo I, Bondone C, et al. SARS-CoV-2-associated coagulopathy and thromboembolism prophylaxis in children: a single-center observational study. J Thromb Haemost. 2021; 19: 522–530.

  • 67

    Lin KY, Kerur B, Witmer CM, et al. Thrombotic events in critically ill children with myocarditis. Cardiol Young 2014; 24: 840–847.

  • 68

    Goldenberg NA, Sochet A, Albisetti M, et al. Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness. J Thromb Haemost. 2020; 18: 3099–3105.

  • 69

    Biss TT, Brandão LR, Kahr WH, et al. Clinical probability score and D-dimer estimation lack utility in the diagnosis of childhood pulmonary embolism. J Thromb Haemost. 2009; 7: 1633–1638.

  • 70

    Children’s Hospital of Philadelphia. Multisystem inflammatory syndrome (MIS-C) – Differential diagnosis – Clinical pathway: emergency, ICU and inpatient. Available from: https://www.chop.edu/clinical-pathway/multisystem-inflammatory-syndrome-mis-c-differential-diagnosis [accessed: February 11, 2021].

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Jan 2021 0 0 0
Feb 2021 0 0 0
Mar 2021 0 0 0
Apr 2021 0 1431 2339
May 2021 0 285 864
Jun 2021 0 33 196
Jul 2021 0 0 0