Multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome (PIMS) is an emerging pediatric disease occurring after prior SARS-CoV-2 infection and is therefore strongly associated with the ongoing COVID-19 pandemic. 

Terminology

The World Health Organization and the US Centers for Disease Control and Prevention both use the name multisystem inflammatory system in children (MIS-C) for this condition, and thus so will this article, but terminology varies. The UK Royal College of Pediatrics and Child Health uses the name pediatric multisystem inflammatory syndrome temporally associated with Covid-19 (abbreviated PIMS or PIMS-TS) ⁴.

Clinical presentation

MIS-C is typically defined by the following 6 key symptoms ¹: 

• pediatric age

• persistent fever

• raised inflammatory laboratory markers

• signs or symptoms of organ dysfunction

• no likely alternative diagnosis

• temporal relation to COVID-19 infection or exposure

Typically MIS-C occurs with at least 1 to 2 weeks delay after the triggering SARS-CoV-2 infection ². 

Vomiting and abdominal complaints are commonly observed in MIS-C. Neutrophilia and lymphocytopenia are also frequent findings. Among laboratory markers, the marked elevation of procalcitonin, IL-6, and troponin are common ¹.

Overweight children are considered to be particularly at risk of developing MIS-C. 

Pathology

Hyperinflammatory systemic shock due to the prior infection is considered to be the culprit behind MIS-C. The severity of the prior COVID-19 infection is not considered to be a strong predictor, as MIS-C can develop even after completely asymptomatic infections ¹. 

Radiographic features

MIS-C affects multiple anatomical structures; thus, in the following section, findings are summarized based on body regions: 

Cardiac

On echocardiography, decreased ejection fraction is the most frequent finding ¹. Pericardial effusions and pericarditis can also occur. On contrast-enhanced cardiac CT, coronary artery dilation and/or coronary artery aneurysms may be encountered ³.

Chest

Pulmonary involvement can manifest as consolidations, focal atelectasis, or, more rarely, as pleural effusions. On chest x-ray, perihilar interstitial involvement and peribronchial cuffing are the most common findings, with more pronounced perihilar airspace opacities and lung edema in severe cases.

Abdominal

Abdominal US may show ascites, signs of intestinal inflammation (predominantly distal ileal and cecal bowel wall thickening), or mesenteric adenopathy (primarily in the right iliac fossa). Increased periportal echogenicity, pericholecystic edema, moderate gallbladder wall thickening, sludge, hepatomegaly or splenomegaly, hypoechoic splenic lesions/infarcts are less common. Acute kidney injury, manifesting as increased echogenicity, occurs occasionally. On abdominal CT, mesenteric fat stranding, along with typical right lower quadrant lymphadenopathy, may be seen ³.

Neurologic

CT/MRI brain exams are typically normal. However, arterial infarction has been reported ³.  

Musculoskeletal

Musculoskeletal involvement occurs occasionally, primarily as myositis ^2,3. 

Treatment and prognosis

According to experience, prompt corticosteroid and intravenous immunoglobulin therapy are the mainstays in the management of MIS-C. Cardiovascular involvement is very common, with almost 50% of patients requiring vasopressor or vasoactive support according to one study ². Multiple studies put the risk of fatal outcome in the range of 1.7-1.8% ¹. 

Differential diagnosis

Kawasaki disease and toxic shock syndrome are considered to be the main clinical mimickers of MIS-C ¹.