(520) HLH Secondary to EBV in a Patient With Sickle Cell Disease Treated With Anakinra Monotherapy

Introduction: Diagnosing hemophagocytic lymphohistiocytosis (HLH) in patients with sickle cell disease (SCD) is challenging given the many overlapping features seen in sepsis, HLH, and severe vaso-occlusive crises (VOC). Although scarce, there are case reports of patients with SCD diagnosed with secondary HLH.

Description: An 18-year-old male with hemoglobin (Hb) SS disease and asthma was admitted for fever and acute chest syndrome. He was transferred to our hospital and intubated for refractory shock with associated multiorgan failure, bone marrow suppression, liver dysfunction, rhabdomyolysis, and acute kidney injury requiring dialysis. Given the severity of his illness, he underwent an exchange transfusion to reduce sickling in VOC followed by three rounds of plasma exchange for thrombocytopenia-associated multiorgan failure and suspected hepatic sequestration. Despite initial improvements, his temperature remained above 39 degrees Celsius while on broad spectrum antibiotics and antipyretics, with negative cultures. Pertinent labs were an admission hemoglobin of 6.8 g/dL (baseline 10 g/dL), platelets 23x10^9/L, a rapidly rising ferritin (from 1,148 ng/mL to 8,081 ng/mL), and triglycerides 354 mg/dL. He met HLH-2004 diagnostic criteria after testing returned with significant elevations in both IL-2 (6,100 U/mL) and CXCL-9 (32,852 pg/mL). Infectious workup revealed positive EBV EBNA, IgM, and IgG antibodies with a viral load of 67,763 IU/mL, leading to a diagnosis of EBV-induced secondary HLH.  He defervesced and clinically improved following treatment with anakinra. His EBV titer downtrended, so common EBV-associated HLH treatment with steroids and rituximab was deferred.

Discussion: HLH should be considered in patients admitted for VOC and multiorgan failure unresponsive to typical therapies. There are limited case reports of HLH in SCD associated with viruses and bacterial sepsis. All cases were treated with steroids, some with the addition of intravenous immunoglobulin or etoposide. We describe a diagnostically challenging case of HLH secondary to primary EBV infection in a patient with Hb SS disease. Further unique to this case was the patient’s improvement on anakinra monotherapy, sparing him from the side effects of a prolonged steroid course and additional immunosuppression.