key: cord-0797714-5a64thzi
authors: Kanthimathinathan, Hari Krishnan; Scholefield, Barnaby R
title: Pediatric Inflammatory Multisystem Syndrome: Time to Collaborate
date: 2020-09-18
journal: J Pediatric Infect Dis Soc
DOI: 10.1093/jpids/piaa105
sha: 620f598749f56ab6aa2e2a690862d4d6036c9a18
doc_id: 797714
cord_uid: 5a64thzi

There is significant variability in the names and case definition of pediatric inflammatory multisystem syndrome associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Such variability leads to adverse consequences in the quest for further knowledge and management strategies. It is time to collaborate to gain consensus.

A recently described hyperinflammatory syndrome in children with overlapping features of Kawasaki disease (KD) and toxic shock syndrome associated with the coronavirus disease 2019 (COVID-19) pandemic has caused significant concern in the pediatric medical community [1] . As a newly described condition, clarity in the name and case definition is important. However, in just over 2 months of being first described, there is already significant variability in both name and case definition (Table 1) [2] [3] [4] [5] [6] . Although "pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 pandemic (PIMS-TS)" and "multisystem inflammatory syndrome in children (MIS-C)" are the most commonly used names; another is "SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome (SCiKH syndrome)" [7] .

Using different nomenclature and case definitions for the same condition is not only confusing for healthcare professionals and the public but also introduces significant difficulties with case ascertainment, aggregation of medical literature, comparison of management strategies, and reporting outcomes. Moreover, introduction of a term such as "likeness" of an existing disease can inadvertently raise anxiety in patients already diagnosed and their families, for example, the eponymous KD, an already rare but important cause of acquired heart disease in children. Only relatively minor variations related to age ranges, characterization of fever, number of organ systems involved, and association with SARS-CoV-2 exposure or testing are evident from the different case definitions (Table 1) . However, a review of the literature highlights instances where only 58% of patients described in 1 case series would have also met an alternative case definition [8] . Hence, the differences cannot be considered trivial or insignificant. Using latent class analysis, Godfred-Cato et al were able to identify 3 distinct presentations among patients reported to have met the Centers for Disease Control and Prevention's case definition for MIS-C [9] . They highlighted that the broad inclusive case definition may have meant that at least some patients with acute COVID-19 and KD may have been reported as MIS-C. It is clear that the existing scenario aids confusion rather than clarity.

Treatment strategies for these children have ranged from intravenous immunoglobulins, a variety of steroids, anakinra, tocilizumab, rituximab, infliximab, and antiplatelets at a variety of doses [8, 9] . In order to improve care for children with this condition, further clarity about the best treatment modality is required. While clinical trials are being planned, a comparative effectiveness study-the "best available treatment study" has been proposed [10] . However, the utility of such initiatives would be adversely impacted by the differences in case definitions as the confusion regarding case ascertainment may lead to difficulties in analyzing the utility of therapies.

The World Health Organization has identified best practices for the naming of new infectious diseases [11] . These principles were applied when SARS-CoV-2 and COVID-19 were named early in the current pandemic. With current widespread availability of both SARS-CoV-2 antigen and antibody testing compared with availability in April 2020-May 2020 when many of the definitions were originally proposed, a clearer link to SARS-CoV-2 infection, rather than merely a temporal association, is often established. However, the usefulness of SARS-CoV-2 antibodies as part of diagnostic criteria may be limited as the pandemic spreads further [9] . The majority of children may acquire the infection and therefore the antibody in the months and years to come. We suggest that a uniform name and precise case definition are essential, urgent, and achievable immediately, perhaps using a consensus gathering process such as the Delphi. We call upon organizations, societies, clinicians, and pediatric researchers to collaborate to achieve much needed consensus. 

Hyperinflammatory shock in children during COVID-19 pandemic

Guidance-paediatric multisystem inflammatory syndrome temporally associated with COVID-19

Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease

Multisystem inflammatory syndrome in children and adolescents with COVID-19: scientific brief

British Paediatric Surveillance Unit team. BPSU study-multisystem inflammatory syndrome, Kawasaki disease and toxic shock syndrome

Canadian Paediatric Surveillance program. Case definition for COVID-19 study

SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome: a novel COVID phenotype in children

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

COVID-19-associated multisystem inflammatory syndrome in children-United States

Best available treatment study for inflammatory syndromes associated with SARS-CoV-2

Naming diseases: first do no harm