SARS-CoV-2-Triggered Hemophagocytic Lymphohistiocytosis with Complications of Posterior Reversible Encephalopathy SyndromeRoss M. Perry, M.D. a* | Scott D. Casey, M.D., M.S. b | Alex Q. Lee, M.D.a | Sylvia P. Bowditch, M.D.c | Mary A. Rasmussen, M.D.c | Viyeka Sethi, M.D. d| Arun R. Panigrahi, M.D. eaUniversity of California, Davis, School of Medicine, Sacramento, California, USA; bDepartment of Emergency Medicine, University of California, Davis, Sacramento, California, U.S.A.; cDepartment of Pediatrics, University of California, Davis, Sacramento, California, U.S.A;dDepartment of Pediatric Critical Care Medicine, University of California, Davis, Sacramento, California, U.S.A;eDepartment of Pediatric Hematology & Oncology, University of California, Davis, Sacramento, California, U.S.A*Correspondence to:Ross Perry, M.D., 14 Rock Lane, Berkeley, CA, 94708, Phone: (707) 331-4626, Fax: (510) 752-1571, E-mail: [email protected] Text Word Count: 850Tables: 1; Figures: 1Short Title: SARS-CoV-2-Triggered HLH Complicated by PRESKeywords: SARS-CoV-2, HLH, PRES, MIS-C, corticosteroids, anakinra

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome of immune dysregulation that is classified into primary and secondary forms. The standard of care is established with dexamethasone and etoposide, but there are currently no guidelines for refractory HLH or cases triggered by infection or malignancy. [1] We describe here a series of pediatric patients with malignancy-associated HLH (m-HLH) to discuss the complexities in the initial diagnostic considerations, the balance of therapeutic regimens and their toxicities, and the novel use of emapalumab and ruxolitinib in patients with refractory disease.