April Choi, Medical Student, Case Western Reserve University School of Medicine, Cleveland, OH
Prompt treatment with etoposide and dexamethasone should be initiated when there is high clinical suspicion for Hemophagocytic Lymphohistiocytosis (HLH) based on the recently validated HScore, even when the diagnostic criteria outlined by HLH-2004 is not met at the time of presentation.
A 54 year old Caucasian female initially presented to the ED with frequent falls and altered mental status. She stated that a physician has told her that her liver is failing. Patient was transferred to Cleveland Medical Center for workup of her liver failure. Subsequent labs performed over the course of two days found her to be pancytopenic (1.3>9.2/26.9<68), hyponatremic, and with elevated liver enzymes (AST 986, ALT 332, Alk Phos 970). Notably, she had significantly elevated ferritin (>9000 ug/L), elevated triglyceride (376 mg/dL), and low fibrinogen (53mg/dL). She was also found to be EBV positive. Preliminary results of the liver biopsy showed hemophagocytosis; she was promptly started on the treatment regime outlined in the HLH-94 protocol. With the initiation of etoposide, ferritin level dropped to 200 ug/L, and her overall health seemed to improve somewhat. Unfortunately, etoposide treatment was held after cycle 4 due to concern for low blood counts. Few days later, she developed a pulmonary embolism which led to severe and persistent tachypnea and tachycardia. She passed away few days after.
Hemophagocytic Lymphohistiocytosis (HLH) is a disease of abnormal immune activation leading to excessive inflammation and destruction. While it can affect patients of all ages, it is mostly found in infants up to 18 months old. The Histiocyte Society set forth an updated diagnostic guidelines for HLH which involves a molecular diagnosis consistent with HLH or 5 of 8 of the following: fever, splenomegaly, cytopenias affecting >2 lineages, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low NK cell activity, ferritin >5000 ug/L, sCD25 >2400 U/mL. However, in an acute setting, results of NK cell activity, sCD25, and molecular HLH diagnosis are difficult to obtain. This leads to us having to meet 5 out of merely 6 “feasible” criteria. During the first 13 days of hospitalization, she was only able to meet 4 of the criteria. However, HScore set forth in 2014 utilizes 9 weighted variables which relies less on the hard-to-obtain values. Our patient's HScore was calculated to be 265 which translates to 99.7% probability of having HLH. The HScore justified the use of etoposide despite not meeting the HLH-2004 criteria. While our patient did not survive, utilization of the HScore may aid the decision to start preemptive etoposide in other suspected HLH patients.