(479) Secondary Hemophagocytic Lymphohistiocytosis From Lymphocytic Choriomeningitis Virus Infection

Introduction: Lymphocytic Choriomeningitis Virus (LCMV) is a rodent-borne virus with 70.5% mortality mostly from multi-organ failure (MOF) in immunocompromised patients. We report a case of a heart recipient who developed Hemophagocytic Lymphohistiocytosis (HLH) and possible complement-mediated Thrombotic Microangiopathy (cmTMA), secondary to LCMV infection.

Description: A 65-year-old heart recipient was admitted for altered mental status (AMS), failure to thrive, and was found to have a urinary tract infection with sepsis on post-operative day 40. Brain imaging and cerebral spinal fluid (CSF) were normal. Hospital course was complicated with generalized tonic-clonic seizures, and respiratory arrest. Repeat brain MRI showed rhombencephalitis. Tacrolimus was discontinued because of possible posterior reversible encephalopathy syndrome. The patient further developed thrombocytopenia, polymicrobial bacteremia and fungemia, reactivation of CMV and EBV, and shock, despite broad-spectrum antibiotics and organ support. Workup for thrombocytopenia indicated elevated C5b-9, which could be suggestive of cmTMA. By day 60, additional workup noted LCMV disease, and the patient had fevers, pancytopenia, hypertriglyceridemia, elevated ferritin (34,715 ng/mL), and elevated soluble IL-2 receptor alpha levels, consistent with secondary HLH syndrome. Patient was treated with eculizumab for possible cmTMA, high dose steroids for HLH, and rituximab and intravenous immunoglobulins for EBV. Unfortunately, his clinical condition worsened and was transitioned to comfort care. Autopsy demonstrated subpial gliosis with macrophages in the leptomeninges and hemophagocytosis in the bone marrow.

Discussion: There have been five clusters of donor-derived LCMV transmissions reported with clinical features of sepsis, AMS, and progression to MOF. Our patient’s HLH was likely triggered by LCMV viremia, and complicated with EBV/CMV reactivation. Viral mediated complement activation resulted in additional possible cmTMA. Although the patient’s clinical markers started to show some improvement with treatment, the patient had profound MOF by then. As we continue to increase organ transplantation, it is important to keep LCMV infection and the MOF clinical syndromes (HLH and cmTMA) that result in intensive care treatment.