Interim guidance on multisystem inflammatory syndrome in children by AAP

CDC issued a health advisory on multisystem inflammatory syndrome in children. Multisystem inflammatory syndrome in children is defined as 'an individual aged less than 21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with 2 or >2 multisystem organ involvement, no alternative plausible diagnoses and being positive for current or recent SARS-CoV-2 (COVID-19) infection by RT-PCR, serology, or antigen test or an exposure within the 4 weeks prior to the onset of symptoms.

Persistent fever, inflammation and evidence of organ dysfunction or shock are the main signs and symptoms of the disease. Other presentations are Kawasaki disease-like features with conjunctivitis, red eyes, red or swollen hands and feet, rash; red cracked lips, swollen glands. Sometimes, children presenting with Kawasaki disease-like syndrome have been found to have a broader age range and they presented with more gastrointestinal symptoms. Others like Toxic shock syndrome-like features, Cytokine storm/macrophage activation, Abnormal clotting, poor heart function, diarrhea and gastrointestinal symptoms, acute kidney injury, and Shortness of breath suggestive of congestive heart failure were also noted. Respiratory symptoms as seen in adults may not be seen in children.

Lab findings found are abnormal level of serum inflammatory markers, elevated B-type natriuretic peptide, hyponatremia, elevated D-dimers.

Initial evaluation should include measurement of vital signs, assessment of perfusion and oxygen saturation. Early consultation and coordination for optimal testing and management should be considered. Laboratory screening for systemic inflammation may also be considered. Severely ill-appearing patients and those in compensated shock or shock should be evaluated and treated in the emergency department/critical care setting. Multidisciplinary team managing the patient can prepare families for an expanded laboratory and cardiac workup which include Chest radiograph, echocardiogram, EKG, Expanded laboratory tests, COVID 19 RT-PCR assay and serologic testing.

Recommended treatment approach for MIS-C include:

• IVIG, 1 to 2 grams/kg(cardiac function and fluid status influence timing of therapy).

• steroid therapy (ranging from 2 to 30 mg/kg/day of methylprednisolone depending on severity of illness) and biologics (eg, anakinra, 2 to 10 mg/kg/day, subcutaneously or intravenously, divided every 6 to 12 hours).

• concurrent antibiotic therapy.

• Hematology consultation for assessment of clotting risk and treatment/prophylaxis is recommended

• Patients treated with steroids and/or biologics often go home with a 3-week taper of steroids and/or biologics.

Suspected MIS-C should be under investigation for COVID-19 regularly. Local infection control policies should be followed. They should have close outpatient pediatric cardiology follow-up starting 2 to 3 weeks after discharge.  

Recommended follow up

Patients in whom MIS-C has been diagnosed should have close outpatient pediatric cardiology follow-up starting 2 to 3 weeks after discharge.

1Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours.

2Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin.

References-

American College of Rheumatology. Clinical guidance for pediatric patients with multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 and hyperinflammation in COVID-19.

Centers for Disease Control and Prevention. Multisystem Inflammatory Syndrome (MIS-C).

Children's Hospital of Philadelphia. Emergency Department, ICU and Inpatient Clinical Pathway for Evaluation of Possible Multisystem Inflammatory Syndrome in Children (MIS-C).

Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York state. Published online ahead of print, June 29, 2020 Jun 29. N Engl J Med. 2020;10.1056/NEJMoa2021756. doi:10.1056/NEJMoa2021756.

Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. Published online ahead of print June 29, 2020. N Engl J Med. 2020;10.1056/NEJMoa2021680. doi:10.1056/NEJMoa2021680.

Whitaker E, Bamford A, Kenny J, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. Published online June 8, 2020. doi:10.1001/jama.2020.10369.