Pediatric Inflammatory Multisystem Syndrome: Statement by the Pediatric Section of the European Society for Emergency Medicine and European Academy of Pediatrics

Abstract

A rise in cases with a new hyperinflammatory disease in children has been reported in Europe and in the Unites States of America, named the Pediatric Inflammatory Multisystem Syndrome—temporally associated with SARS-CoV-2 (PIMS-TS). There appears to be a wide spectrum of signs and symptoms with varying degrees of severity, including a toxic shock like presentation with hypovolaemia and shock, and a Kawasaki-like presentation with involvement of the coronary arteries. Most of these children have evidence of a previous infection with SARS-CoV-2, or a history of significant exposure, but not all. Limited data exist on the incidence of PIMS-TS, but it remains a rare condition. Early recognition and escalation of care is important to prevent the development of serious sequelae, such as coronary artery aneurysms. Clinicians assessing febrile children in primary and secondary care should include PIMS-TS in their differential diagnoses. In children fulfilling the case definition, additional investigations should be undertaken to look for evidence of inflammation and multiorgan involvement. Suspected cases should be discussed with experts in pediatric infectious diseases at an early stage, and advice should be sought from critical care in more severe cases early. There is limited consensus on treatment; but most children have been treated with immunoglobulins or steroids, and with early consideration of biologicals such anti-TNF and anti-IL1 agents. Treatment should ideally be within the context of controlled treatment trials. Clinicians are encouraged to document and share their cases using research registries.

Vitamin D in Corona Virus Disease 2019 (COVID-19) Related Multisystem Inflammatory Syndrome in Children (MIS-C)

“…Since MIS-C generally occurs 3 to 4 weeks after a SARS-CoV-2 infection, consists a host-dependent reaction to a past infections ( 41 ), and this is compatible with antibody- and/or immunocomplex-mediated disease ( 42 ), we speculate that in this condition, vit D most likely plays an immunomodulatory role rather than an antiviral one. Furthermore, in the acute phase of MIS-C has been observed high levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-17, interferon-gamma (IFN-γ) and differential T and B cell subset lymphopenia ( 43 ).…”

Haemophagocytic syndrome and COVID-19

“…In April 2020, the Royal College of Paediatrics and Child Health in the UK described a paediatric syndrome that was called Paediatric Inflammatory Multisystem Syndrome—temporally associated with SARS-CoV-2 (PIMS-TS) [ 10 ]; in the USA, this syndrome was referred as Multisystem Inflammatory Syndrome in children (MIS-C) [ 11 ], and an additional definition was further provided by the World Health Organization [ 12 ]. The three case definitions are similar and describe a population of children with evidence of a preceding SARS-CoV-2 infection (or exposure to a suspected or confirmed case) presenting with persistent fever, clinical features and laboratory abnormalities reflecting ongoing inflammation, and systemic involvement (including especially cardiac involvement) in the absence of other reasonable aetiologies [ 13 ]. In a recently reported consensus, patients with MIS-C have been classified into two main phenotypes (nonspecific phenotype, and Kawasaki disease-like phenotype) [ 14 ], although the distinction was mainly based on expert opinion rather than in a clearly-proven differentiated clinical and biological profile [ 15 ].…”

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

“…At present, professionals remain confronted with substantial uncertainties regarding clinical phenotypes, long-term outcomes, and optimal management ( 20 ). In the absence of randomized trials, evidence for best treatment is minimal for the diagnostic, anti-inflammatory, anti-infectious, and supportive measures which have been proposed ( 9 , 21 ). Recommendations therefore are based primarily on expert opinion and similar recommendations in the United Kingdom.…”