P2A285: A Neonate with Cytokine Storm Managed with Steroids, Plasmapheresis, and Tocilizumab

Introduction: Cytokine storm in neonates is a known but uncommon condition. There is an increased report of neonatal inflammatory conditions during the COVID-19 pandemic. An increase in interleukin-6 (IL-6) levels may lead to hyperinflammation in neonates leading to multiple organ failure. Tocilizumab is a humanized monoclonal antibody that can prevent systemic inflammatory responses by blocking IL-6-mediated proinflammatory signaling. We report a case of a neonate with hyper IL-6 treated with steroids, plasmapheresis, and tocilizumab that led to a favorable outcome.

Case Description: A male neonate born at 39 weeks gestation via elective C-section was transferred to the PICU for initiation of extracorporeal life support in the setting of persistent pulmonary hypertension, cardiogenic shock, transaminitis, and metabolic acidosis due to meconium aspiration syndrome. Upon arrival, the patient was started on extracorporeal membrane oxygenation (ECMO) support and was transitioned to conventional mechanical ventilation after 12 days. Due to worsening thrombocytopenia and oxygenation (decreasing S/F ratio) and elevated C-reactive protein and ferritin (851 micg/L), steroids and plasmapheresis were initiated 3 days after the ECMO run (Figure). Since the patient was showing signs of severe inflammation, including IL-6 levels of 400 pg/ml, 56 mg of tocilizumab was administered intravenously after 4 days of plasmapheresis. Microbiological cultures and Karius test were negative. He was treated with multiple courses of antibiotics and antifungals for presumed sepsis. Following the infusion of tocilizumab, there were marked improvements in platelet levels, S/F ratio, and CRP. COVID-19 testing was negative. Genetic and metabolic testing were normal. The patient was discharged home two months later in stable condition. Maternal history was significant for positive Group B Strep and negative COVID-19.

Discussion: We present a neonate who developed thrombocytopenia, worsening organ failure, and hyperinflammation and improved clinically with steroids, plasmapheresis, and tocilizumab. IL-6 level was measured before starting the plasmapheresis and was found to be elevated which prompted us to give a dose of tocilizumab. IL-6 is a known mediator of inflammation in neonates. It is also increased in fetal inflammatory response syndrome. Hyperinflammation may be due to sepsis, an autoimmune condition, or an innate response. We ruled out active infection leading to hyperinflammation in this neonate. Steroids act at various stages of inflammatory cascade. Plasmapheresis is an accepted therapy for thrombocytopenia-associated multiple organ failure in children. Tocilizumab, an IL-6 receptor blocker is approved for many conditions with elevated IL-6 levels and has been used in hyperinflammation associated with COVID-19.

Conclusion: Neonates with multiple organ failure should be evaluated for hyperinflammatory conditions. Potential therapeutic options in children with hyperinflammation such as steroids, plasmapheresis, and cytokine-blocking medications may be considered depending on the underlying cause and cytokine profile.