The challenges of multisystem inflammatory syndrome diagnosis and treatment

A two-year-old girl with fever, diarrhea and vomiting was presented to the Emergency Department (ED). A maculopapular rash on the face, cervical lymphadenopathy and 1st degree dehydration were being noted. Laboratory results showed leukocytosis, neutrophilia and a high level of C-reactive protein (CRP). Amoxicillin was prescribed, but the patient’s state did not improve. She returned to ED with rash all over her body and 2nd degree dehydration. Laboratory results revealed thrombocytopenia and a more increased level of CRP. It was found that her mother has been diagnosed with the coronavirus disease approximately two months ago. Extended laboratory results showed signs of mild anemia, increased levels of liver enzymes, procalcitonin, troponin, N-terminal prohormone of brain natriuretic peptide, D-dimers, ferritin. Anti-SARS-CoV-2 (severe acute respiratory syndrome-coronavirus) IgG (immunoglobulin G) were detected. Multisystem inflammatory syndrome was diagnosed. Pediatric echocardiography revealed 10 mm of fluids in pericardium, I degree mitral valve regurgitation, dilated left coronary artery. She was given a treatment with intravenous Immunoglobulin G, methylprednisolone and aspirin, but her state did not improve. A treatment with Tocilizumab was given, but it did not have a much more positive effect, laboratory results showed progressed leucocytosis and neutrophilia. As the last resort, biology treatment with a recombinant form of human interleukin-1 receptor antagonist Anakinra was started and after a week all symptoms changed, and laboratory results regressed.

Multisystem inflammatory syndrome; Coronavirus; Prolonged fever; Dilated coronary artery

[1] Mohan BS, Nambiar V. COVID-19: an insight into SARS-CoV-2 pandemic originated at Wuhan city in Hubei province of China. Journal of Infectious Diseases and Epidemiology. 2020; 6: 146.

[2] Kutsuna S. Clinical manifestations of coronavirus disease 2019. JMA Journal. 2021; 4: 76–80.

[3] Götzinger F, Santiago-García B, Noguera-Julián A, Lanaspa M, Lancella L, Calò Carducci FI, et al. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. The Lancet Child & Adolescent Health. 2020; 4: 653–661.

[4] European Centre for Disease Prevention and Control. Rapid risk assessment: paediatric inflammatory multisystem syndrome and SARS-CoV-2 infection in children. 2020. Available at: https: //www.ecdc.europa.eu/en/publications-data/paediatric-inflammatory-multisystem-syndrome-and-sars-cov-2-rapid-risk-assessment (Accessed: 17 December 2020).

[5] Ionescu MD, Taras R, Dombici B, Balgradean M, Berghea EC, Nicolescu A. The challenging diagnosis of pediatric multisystem inflammatory syndrome associated with Sars-Cov-2 infection-two case reports and literature review. Journal of Personalized Medicine. 2021; 11: 318.

[6] Esposito S, Principi N. Multisystem inflammatory syndrome in children related to SARS-CoV-2. Paediatric Drugs. 2021; 23: 119–129.

[7] Miller J, Cantor A, Zachariah P, Ahn D, Martinez M, Margolis KG. Gastrointestinal symptoms as a major presentation component of a novel multisystem inflammatory syndrome in children that is related to coronavirus disease 2019: a single center experience of 44 cases. Gastroenterology. 2020; 159: 1571–1574.e2.

[8] Rouva G, Vergadi E, Galanakis E. Acute abdomen in multisystem inflammatory syndrome in children: a systematic review. Acta Paediatrica. 2022; 111: 467–472.

[9] Gupta N, Talathi S. Factors differentiating multisystem inflammatory syndrome in children (MIS-C) from severe/critical COVID-19 infection in children. Indian Pediatrics. 2022; 59: 120–124.

[10] Gupta A, Gill A, Sharma M, Garg M. Multi-system inflammatory syndrome in a child mimicking Kawasaki disease. Journal of Tropical Pediatrics. 2021; 67: fmaa060.

[11] Greco A, De Virgilio A, Rizzo MI, Tombolini M, Gallo A, Fusconi M, et al. Kawasaki disease: an evolving paradigm. Autoimmunity Reviews. 2015; 14: 703–709.

[12] Godfred-Cato S, Abrams JY, Balachandran N, Jaggi P, Jones K, Rostad CA, et al. Distinguishing multisystem inflammatory syndrome in children from COVID-19, Kawasaki disease and toxic shock syndrome. The Pediatric Infectious Disease Journal. 2022; 41: 315–323.

[13] Mavrogeni SI, Kolovou G, Tsirimpis V, Kafetzis D, Tsolas G, Fotis L. The importance of heart and brain imaging in children and adolescents with multisystem inflammatory syndrome in children (MIS-C). Rheumatology International. 2021; 41: 1037–1044.

[14] Alsaied T, Tremoulet AH, Burns JC, Saidi A, Dionne A, Lang SM, et al. Review of cardiac involvement in multisystem inflammatory syndrome in children. Circulation. 2021; 143: 78–88.

[15] Hejazi OI, Loke YH, Harahsheh AS. Short-term cardiovascular complications of multi-system inflammatory syndrome in children (MIS-C) in adolescents and children. Current Pediatrics Reports. 2021; 9: 93–103.

[16] Aydın F, Çelikel E, Ekici Tekin Z, Coşkun S, Sezer M, Karagöl C, et al. Comparison of baseline laboratory findings of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis and multisystem inflammatory syndrome in children. International Journal of Rheumatic Diseases. 2021; 24: 542–547.

[17] Capone CA, Misra N, Ganigara M, Epstein S, Rajan S, Acharya SS, et al. Six month follow-up of patients with multi-system inflammatory syndrome in children. Pediatrics. 2021; 148: e2021050973.

[18] Farooqi KM, Chan A, Weller RJ, Mi J, Jiang P, Abrahams E, et al.; Columbia University Interdisciplinary MIS-C Follow-up Program and the CUIMC Pediatric/Adult Congenital Heart Research Collaborative. Longitudinal outcomes for multisystem inflammatory syndrome in children. Pediatrics. 2021; 148: e2021051155.