Yıldız EKEMEN KELEŞ, Dilek YILMAZ ÇİFTDOĞAN

Çocuklarda Çoklu Sistemik İnflamatuvar Sendrom

2019 yılı Aralık ayında Çin’de nedeni bilinmeyen pnömoni salgını meydana geldi ve ciddi akut solunum yetmezliği sendromu koronavirüs 2’nin (SARSCoV- 2) neden olduğu hastalığa Koronavirüs hastalığı 2019 (COVID-19) adı verildi. Koronavirüs hastalığı 2019 çocuklarda erişkinlere kıyasla daha az sıklıkla görülmekte ve daha hafif bulgularla seyrettiği bilinmektedir. Fakat Avrupa’da Nisan 2020’nin sonlarında SARS-CoV-2 enfeksiyonu geçiren bazı çocuklarda ateş, karın ağrısı, şok, miyokardiyal yetmezlik ve yoğun bakımı ihtiyacı geliştiği görülmüştür. Bu yeni hastalığa Çoklu Sistemik İnflamatuvar Sendrom (MIS-C) adı verilmiştir. MIS-C’in patogenezi net olmamakla birlikte immün sistemin kontrolsüz inflamasyonu sonucunda çoklu organ tutulumuna ait bulgularla seyretmekte ve hatta ölüme neden olmaktadır. Bu nedenle MIS-C’li hastaların tanı ve tedavilerinin hızlıca yönetilmesi gerekmektedir. Bu derlemede MIS-C hastalığının patofizyolojisi, klinik ve laboratuvar bulguları, tanı yöntemleri ve tedavi rejimleri irdelenmiştir.

Anahtar Kelimeler:

COVID-19, çocuk, SARS-CoV-2, çoklu sistemik inflamatuvar sendrom, tanı, tedavi

Multisystem Inflammatory Syndrome in Children

An outbreak of pneumonia of unknown origin occurred in China in December 2019. The disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was named Coronavirus disease 2019 (COVID- 19). COVID-19, which is seen less frequently in children than adults, is known to have milder symptoms. However, at the end of April 2020 in Europe, it was observed that some children with SARS-CoV-2 infections developed fever, abdominal pain, shock, myocardial insufficiency, and the need for intensive care. This new disease has been called Multisystem Inflammatory Syndrome in Children (MIS-C). Although the pathogenesis of MIS-C is unclear, it progresses with signs of multi-organ involvement as a result of uncontrolled inflammation of the immune system and even causes death. Therefore, the diagnosis and treatment of patients with MIS-C should be managed quickly. In this review, the pathophysiology, clinical and laboratory findings, diagnostic methods, and treatment regimens of MIS-C were discussed.

Keywords:

COVID-19, child, SARS-CoV-2, multisystem inflammatory syndrome, diagnose, treatment,

PDF

___

Kaynaklar 1. World Health Organization (WHO). WHO Director-General's opening remarks at the media briefing on COVID-19 -- 11 March 2020. Available at: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-COVID-19---11-march-2020 (Accessed on May 01, 2020).
2. Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020;145(6):e20200702. doi 10.1542/peds.2020-0702.
3. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet. 2020;395(10239):1771-8. doi: 10.1016/S0140-6736(20)31103-X.
4. Viner RM, Whittaker E. Kawasaki-like disease: emerging complication during the COVID-19 pandemic. The Lancet. 2020;395(10239):1741-3. DOI10.1016/S0140-6736(20)31129-6.
5. Center for Disease Control and Prevention, Center for Preparedness and Response: Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19), Clinician Outreach and Communication (COCA) Webinar-19 May 2020. Available at: https://emergency.cdc.gov/coca/calls/2020/callinfo_051920.asp?deliveryName=USCDC_1052- DM28623.
6. Pediatric Intensive Care Society. PICS Statement: Increased number of reported cases of novel presentation of multi-system inflammatory disease. April 27, 2020. Available at https://picsociety.uk/wpcontent/uploads/2020/04/PICS-statement-re-novel-KD-C19- presentation-v2-27042020.pdf.
7. Perez-Toledo M, Faustini SE, Jossi SE, Shields AM, Kanthimathinathan HK, Allen JD, et al. Serology confirms SARS-CoV-2 infection in PCR-negative children presenting with Paediatric Inflammatory Multi-System Syndrome. MedRxiv. 2020. doi: 10.1101/2020.06.05.20123117.
8. Weisberg SP, Connors T, Zhu Y, Baldwin M, Lin W-H, Wontakal S, et al. Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19. medRxiv. 2020. doi: 10.1101/2020.07.12.20151068. Preprint.
9. Brodin P. Why is COVID-19 so mild in children? Acta Paediatr. 2020 Jun;109(6):1082-1083. doi: 10.1111/apa.15271. Epub 2020 Apr 15. PMID: 32212348.
10. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465-9. doi: 10.1038/s41586-020-2196-x.
11. Consiglio CR, Cotugno N, Sardh F, Pou C, Amodio D, Rodriguez L, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183(4):968-81. e7. doi: 10.1016/j.cell.2020.09.016.
12. Hamming I, Timens W, Bulthuis M, Lely A, Navis Gv, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. The Journal of Pathology: Rev Med Microbiol. 2004;203(2):631-7. doi: 10.1002/path.1570.
13. Kuba K, Imai Y, Rao S, Jiang C, Penninger JM. Lessons from SARS: control of acute lung failure by the SARS receptor ACE2. J mol med. 2006;84(10):814-20. doi: 10.1007/s00109-006-0094-9.
14. Chang L-Y, Lu C-Y, Shao P-L, Lee P-I, Lin M-T, Fan T-Y, et al. Viral infections associated with Kawasaki disease. J Formos Med Assoc. 2014;113(3):148-54. doi: 10.1016/j.jfma.2013.12.008.
15. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2. doi: 10.1016/S2213-2600(20)30076-X.
16. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation. 2020. doi: 10.1161/cırculatıonaha.120.048360.
17. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem inflammatory syndrome in US children and adolescents. N Engl J Med. 2020;383(4):334-46. doi: 10.1056/NEJMoa2021680.
18. Carlin RF, Fischer AM, Pitkowsky Z, Abel D, Sewell TB, Landau EG, et al. Discriminating MIS-C Requiring Treatment from Common Febrile Conditions in Outpatient Settings. J Pediatr. 2020. doi: 10.1016/j.jpeds.2020.10.013.
19. Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med. 2020;383(4):347-58. doi: 10.1056/NEJMoa2021756.
20. Toubiana J, Poirault C, Corsia A, Bajolle F, Fourgeaud J, Angoulvant F, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. bmj. 2020;369. doi: 10.1136/bmj.m2094.
21. Lishman J, Kohler C, De Vos C, Van Der Zalm MM, Itana J, Redfern A, et al. Acute Appendicitis in Multisystem Inflammatory Syndrome in Children With COVID-19. Pediatr Infect Dis J. 2020;39(12):e472-e3. doi: 10.1097/INF.0000000000002900.
22. Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiri H, et al. American College of Rheumatology Clinical Guidance for Pediatric Patients with Multisystem Inflammatory Syndrome in Children (MIS‐C) Associated with SARS‐CoV‐2 and Hyperinflammation in COVID‐19. Version 2. Arthritis Rheumatol. 2020. doi: 10.1002/art.41616.
23. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. Jama. 2020. doi: 10.1001/jama.2020.10369.
24. Mamishi S, Movahedi Z, Mohammadi M, Ziaee V, Khodabandeh M, Abdolsalehi MR, et al. Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran. Epidemiol Infec. 2020;148. doi: 10.1017/S095026882000196X.
25. Türkiye Cumhuriyeti COVID-19 Çocuk Hasta yönetimi ve Tedavi Rehberi.https://covid19bilgi.saglik.gov.tr/depo/rehberler/covid-19-rehberi/COVID-19_REHBERI_COCUK_HASTA_YONETIMI_VE_TEDAVI.pdf.
26. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet. 2020. doi: 10.1016/S0140-6736(20)31103-X.
27. Godfred-Cato S, Bryant B, Leung J, Oster ME, Conklin L, Abrams J, et al. COVID-19–associated multisystem inflammatory syndrome in children—United States, March–July 2020. Morbidity and Mortality Weekly Report. 2020;69(32):1074. doi: 10.15585/mmwr.mm6932e2.
28. Capone CA, Subramony A, Sweberg T, Schneider J, Shah S, Rubin L, et al. Characteristics, cardiac involvement, and outcomes of multisystem inflammatory syndrome of childhood associated with severe acute respiratory syndrome coronavirus 2 infection. J pediatr. 2020;224:141-5. doi: 10.1016/j.jpeds.2020.06.044.
29. Moraleda C, Serna-Pascual M, Soriano-Arandes A, Simó S, Epalza C, Santos M, et al. Multi-inflammatory syndrome in children related to SARS-CoV-2 in Spain. Clin Infec Dis. 2020. doi: 10.1093/cid/ciaa1042.
30. Shulman S. Pediatric COVID-associated Multi-system Inflammatory Syndrome (PMIS)[Editorial]. J Pediat Inf Disc Soc. 2020. doi: 10.1093/jpids/piaa062.
31. Lin K-H, Chang S-S, Yu C-W, Lin S-C, Liu S-C, Chao H-y, et al. Usefulness of natriuretic peptide for the diagnosis of Kawasaki disease: a systematic review and meta-analysis. BMJ open. 2015;5(4):e006703. doi: 10.1136/bmjopen-2014-006703.
32. Rowley AH. Multisystem inflammatory syndrome in children and Kawasaki disease: two different illnesses with overlapping clinical features. The Journal of Pediatrics. 2020;224:129-32. doi: 10.1016/j.jpeds.2020.06.057.
33. Rowley AH, Shulman ST. The epidemiology and pathogenesis of Kawasaki disease. Front Pediatr. 2018;6:374. doi: 10.3389/fped.2018.00374.
34. Gatterre P, Oualha M, Dupic L, Iserin F, Bodemer C, Lesage F, et al. Kawasaki disease: an unexpected etiology of shock and multiple organ dysfunction syndrome. Intensive Care Med. 2012;38(5):872-8. doi: 10.1007/s00134-012-2473-8.
35. Li Y, Luo C, Li W, Xu Z, Zeng C, Bi S, et al. Structure-based preliminary analysis of immunity and virulence of SARS coronavirus. Viral Immunol. 2004;17(4):528-34. doi: 10.1089/vim.2004.17.528.
36. Gaensbauer JT, Birkholz M, Smit MA, Garcia R, Todd JK. Epidemiology and clinical relevance of toxic shock syndrome in US children. Pediatr Infect Dis J. 2018;37(12):1223-6. doi: 10.1097/INF.0000000000002002.
37. Lin Y-J, Cheng M-C, Lo M-H, Chien S-J. Early differentiation of Kawasaki disease shock syndrome and toxic shock syndrome in a pediatric intensive care unit. Pediatr infect Dis J. 2015;34(11):1163-7. doi: 10.1097/INF.0000000000000852.
38. Grom AA, Horne A, De Benedetti F. Macrophage activation syndrome in the era of biologic therapy. Nat Rev Rheumatol. 2016;12(5):259-68. doi: 10.1038/nrrheum.2015.179.
39. Chesshyre E, Ramanan AV, Roderick MR. Hemophagocytic lymphohistiocytosis and infections: An update. Pediatr infect Dis J.2019;38(3):e54-e6. doi: 10.1097/INF.0000000000002248.
40. Schram AM, Campigotto F, Mullally A, Fogerty A, Massarotti E, Neuberg D, et al. Marked hyperferritinemia does not predict for HLH in the adult population. Blood. 2015;125(10):1548-52. doi: 10.1182/blood-2014-10-602607.
41. Henderson LA, Canna SW, Friedman KG, Gorelik M, Lapidus SK, Bassiri H, 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(11):1791-805. doi: 10.1002/art.41454.
42. 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-e6. doi: 10.1097/INF.0000000000002888.
43. Capra R, De Rossi N, Mattioli F, Romanelli G, Scarpazza C, Sormani MP, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J Intern Med. 2020;76:31-5. doi: 10.1016/j.ejim.2020.05.009.
44. Cheung EW, Zachariah P, Gorelik M, Boneparth A, Kernie SG, Orange JS, et al. Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City. Jama. 2020;324(3):294-6. doi: 10.1001/jama.2020.10374.