Challenges in diagnosing COVID-19 related disease in pediatric patients with rheumatic disease

Abstract

Objectives Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition associated with coronavirus disease 2019 (COVID-19). Here we aimed to raise awareness for the symptoms of MIS-C in patients with rheumatic diseases, emphasizing the challenges of the differential features. Methods We retrospectively evaluated the demographic and clinical characteristics, laboratory and imaging findings, treatments, and outcomes of six MIS-C patients with previous rheumatic disease. Results Three of the patients had familial Mediterranean fever (FMF), one had juvenile dermatomyositis (JDM), one had systemic juvenile idiopathic arthritis (JIA), and another patient had oligoarticular JIA. All FMF patients presented with fever and abdominal pain, two also had chest pain. The patient with systemic JIA presented with fever, rash, and myalgia. All patients had elevated inflammatory markers and high d-dimer levels. Chest imaging of two FMF patients showed infiltrations compatible with pneumonia. One FMF patient had mildly decreased systolic functions with a shortening fraction of 48% in his echocardiography. Intravenous immunoglobulin and methylprednisolone were administered to all patients. Anakinra was given to four patients. Conclusions Clinical and laboratory signs of MIS-C may overlap with the findings of various rheumatic diseases, and this may cause a delay in diagnosis.

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

“…Immune dysregulatory diseases were the fourth most-common IEIs in children who experienced COVID-19 (n = 95, 13.4%) [ 6 , 9 , 19 , 29 , 32 , 35 , 38 , 40 , 43 , 44 , 46 , 48 , 50 , 52 , 54 , 57 , 58 , 62 , 63 , 65 , 67 , 72 – 74 , 79 , 81 , 82 , 84 , 86 , 88 , 93 – 97 , 99 , 100 , 102 , 109 , 110 , 113 , 115 , 118 , 121 , 125 , 130 ] (see Additional file 2 : Table S3). Among them, 25 have familial hemophagocytic lymphohistiocytosis (26.3% of all immune dysregulatory diseases) [ 6 , 19 , 29 , 48 , 62 , 65 , 67 , 72 , 73 , 79 , 81 , 82 , 84 , 88 , 99 , 110 , 125 ], 19 have autoimmune polyendocrine syndromes type-1 (APS-1) (20%) [ 35 , 38 , 73 , 86 , 94 , …”

Overlapping clinical features of systemic juvenile idiopathic arthritis and SARS-CoV-2-related multisystem inflammatory syndrome in children

“…Due to the similar clinical presentation, it is also a challenge to diagnose other COVID-19-related diseases in children with rheumatic diseases, including JIA [ 27 ]. The main characteristics of studies that analysed overlapping clinical features of sJIA and KD or MIS-C are summarised in Table II .…”

“…In addition, the clinical course of MAS in MIS-C was milder, the prognosis better, and required treatment less aggressive than in MAS/sJIA [25]. Due to the similar clinical presentation, it is also a challenge to diagnose other COVID-19-related diseases in children with rheumatic diseases, including JIA [27]. The main characteristics of studies that analysed overlapping clinical features of sJIA and KD or MIS-C are summarised in Table II.…”

Central nervous system manifestations of monogenic autoinflammatory disorders and the neurotropic features of SARS-CoV-2: Drawing the parallels

“…Considering the associated innate immune cell activation with cytokine storm and the overlap in clinical features, MIS-C is often difficult to differentiate from relapse in AID patients. This was demonstrated in a recent case series of three FMF patients with MIS-C, of which all had fever and abdominal pain obscuring the diagnosis (113). Laboratory features that can aid in discriminating MIS-C from AID include thrombocytopenia, lymphocytopenia, and high n-terminal pro hormone B-type natriuretic peptide and D-dimer levels.…”