Paediatric Inflammatory Multisystem Syndrome Temporally-Associated with SARS-CoV-2 Infection: An Overview
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UNDERSTANDING THE DISEASE
Paediatric Inflammatory Multisystem Syndrome Temporally‑Associated with SARS‑CoV‑2 Infection: An Overview Michael J. Carter1,2* , Manu Shankar‑Hari3,4 and Shane M. Tibby1,2 © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
In spring 2020 paediatricians working across Europe and the USA [1] alerted colleagues to clusters of previously healthy children presenting with unremitting fever, multisystem inflammation and pancarditis. This syndrome, initially termed Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 infection (PIMS-TS), or by its US variation Multisystem Inflammatory Syndrome in Children (MIS-C; Table 1), appears to be a rare complication of (largely) asymptomatic SARSCoV-2 infection in children [8]. However, the overlap with other paediatric inflammatory syndromes such as Kawasaki disease (KD) and optimum treatments remain unknown. We provide a narrative overview of PIMS-TS and highlight important knowledge gaps.
What is PIMS‑TS? Cardinal signs of PIMS-TS include fever, stigmata of inflammation (rash, conjunctivitis, and oral mucosal changes), gastrointestinal symptoms, and cardiac dysfunction (Fig. 1A). These features are accompanied by laboratory evidence of significant inflammation: neutrophilia, lymphopaenia, elevated serum CRP and ferritin concentrations; hypercoagulable state; and non-ST elevation pancarditis. Echocardiograms typically reveal left ventricular dysfunction, and hyperechoic coronary arteries. Complications of PIMS-TS include systemic thrombosis [1] and coronary artery aneurysms in approximately 13% of children in published cohorts [4]. Nearly 2% of affected children have died [4]. *Correspondence: [email protected] 1 Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, UK Full author information is available at the end of the article
What are the differential diagnoses of PIMS‑TS? Children with PIMS-TS were initially treated as KD or presumed toxic shock syndrome (TSS) with broad spectrum antibiotics and intravenous immunoglobulins [1, 2]. KD, TSS, occult infection, acute abdominal conditions, and rare inflammatory conditions remain important differentials (Fig. 1 B). However, there are now clinical, microbiological and immunological data describing PIMS-TS as a novel immunopathogenic illness [5, 9, 10]. Similarities between PIMS-TS and KD include ubiquity of fever and high prevalence of oral mucositis, conjunctivitis and rash. In contrast, children with PIMS-TS are often older than 5 years of age (48%), compared with children with KD (18% > five years) [11, 12], and gastrointestinal symptoms, cardiac dysfunction and need for vasoactive infusions are considerably more prevalent. A rare subset of KD patients present with shock syndrome, but these children typically have lower ferritin, troponin and less disordered coagulation than children with PIMS-TS [5]. Approximately 45% of children with PIMS-TS have a positive PCR test for SARS-CoV-2 infection. In addition,
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