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Multisystem Inflammatory Syndrome in Children (MIS-C)

Multisystem Inflammatory Syndrome in Children (MIS-C), also known as Paediatric Inflammatory Multisystem Syndrome (PIMS) or Systemic Inflammatory Syndrome in COVID-19 (SISCoV), is a rare but severe condition associated with SARS-CoV-2 infection. It involves persistent fever and extreme inflammation and can lead to medical emergencies such as shock and organ failure.

Transmission electron micrograph of SARS-CoV-2, the virus responsible for COVID-19.
Transmission electron micrograph of SARS-CoV-2, the virus responsible for COVID-19.

Overview

Children with MIS-C typically present with persistent fever. Initial symptoms often include acute abdominal pain, diarrhoea, and vomiting. Additionally, children may exhibit:

  • Low blood pressure and shock
  • Neurological disturbances
  • Pink eye (conjunctivitis)
  • Rashes
  • Enlarged lymph nodes
  • Swollen hands and feet
  • "Strawberry tongue"

A cytokine storm, where the immune system responds excessively, can also occur, leading to severe complications like heart failure, respiratory distress, and acute kidney injury.

Complications

MIS-C can lead to severe complications, including:

  • Cardiac dysfunction
  • Coronary artery abnormalities, such as aneurysms
  • Acute kidney injury
  • Coagulopathy (increased blood clotting)
Aneurysmal enlargement of the coronary arteries, a complication seen in Kawasaki Syndrome and MIS-C.
Aneurysmal enlargement of the coronary arteries, a complication seen in Kawasaki Syndrome and MIS-C.

Diagnosis

Early recognition and prompt specialist referral are very important. Diagnosis involves:

  • Clinical evaluation by paediatric specialists
  • Blood tests, chest x-ray, heart ultrasound (echocardiography), and abdominal ultrasound
  • Elevated markers of inflammation, such as ESR, C-reactive protein, and procalcitonin
  • Exclusion of other infectious/non-infectious causes, including bacterial sepsis and Kawasaki disease

Preliminary WHO Case Definition

  • Fever >3 days
  • Two of the following: rash or non-purulent conjunctivitis, hypotension/shock, myocardial dysfunction, coagulopathy, acute gastrointestinal problems
  • Elevated inflammatory markers
  • No other cause of inflammation
  • Evidence of COVID-19 (RT-PCR, antigen test, or serology positive)

Treatment

Treatment is tailored to each child and involves multidisciplinary care, including:

  • Anti-inflammatory medications: Intravenous immunoglobulin (IVIG) and corticosteroids
  • Supportive care: Oxygen therapy and mechanical ventilation if necessary
  • Cardiac and respiratory support
  • Anticoagulants and antiplatelet drugs like low-dose aspirin
  • Cytokine blockers (tocilizumab for IL-6, anakinra for IL-1)

Most children respond well to IVIG, with or without corticosteroids. Long-term prognosis remains unclear, and ongoing follow-up by a paediatric cardiology team is recommended to monitor for complications such as coronary artery aneurysms.

Epidemiology

MIS-C is rare, with a fatality rate of less than 2% among reported cases. It often affects children of African, Afro-Caribbean, and Hispanic descent more frequently than those of East Asian ancestry. Clusters of cases typically appear 2–6 weeks after local peaks in COVID-19 transmission.

Pathogenesis and Mechanism

The exact pathogenesis of MIS-C is not fully understood. It is hypothesised that SARS-CoV-2 may trigger a hyperinflammatory response in genetically predisposed children. Potential mechanisms include cytokine storms and antibody-dependent enhancement, where antibodies facilitate viral entry into host cells. Further research is needed to fully elucidate the underlying molecular mechanisms and genetic predispositions.

Note: The condition in adults, known as Multisystem Inflammatory Syndrome in Adults (MIS-A), has also been reported but remains less well-defined.


Self-assessment MCQs (single best answer)

What is another name for Multisystem Inflammatory Syndrome in Children (MIS-C)?



Which virus is associated with MIS-C?



What is a common initial symptom of MIS-C?



Which complication is NOT typically associated with MIS-C?



What is a key feature of the preliminary WHO case definition for MIS-C?



Which treatment is commonly used for MIS-C?



Which demographic is more frequently affected by MIS-C?



Which test is NOT mentioned as part of the diagnostic process for MIS-C?



What is a potential severe outcome of a cytokine storm in MIS-C?



Which of the following is a cytokine blocker that may be used in treating MIS-C?



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