Case Presentation: A 45-year-old woman presented to the Emergency Room with complaints of influenza-like symptoms and neck stiffness for a duration of about one week. Initial laboratory data was significant for acute anemia, thrombocytopenia, transaminitis and elevated inflammatory markers (ferritin, LDH, and D-dimer). Physical exam was significant for a truncal, maculopapular rash with extension to her bilateral thighs and knees. Patient was admitted to the stepdown unit with diagnoses of sepsis due to presumed viral illness and acute hypoxic respiratory failure. Hematology was consulted the following morning for further evaluation of acute cytopenias. The clinical suspicion for HLH was high and a bone marrow biopsy was performed. Preliminary bone marrow results showed a hypercellular marrow with no evidence of hematological malignancy, although two foci of hemophagocytosis were seen. Based on these results, the decision was made to start treatment for presumed HLH with the HLH-94 protocol using dexamethasone followed by addition of etoposide. The morning after dexamethasone was started, patient experienced a witnessed ventricular fibrillation arrest and was intubated for airway protection. Her ICU course was complicated by acute renal failure requiring intermittent dialysis, progressive liver injury, and an acute drop in left ventricular ejection fraction attributed to reverse Takatsubos. The patient showed gradual clinical improvement, allowing for extubation and downgrade from ICU one week later. During her 44-day hospitalization, an extensive work-up was done to determine the underlying cause of her HLH. This work-up was significant for a recent prescription for Lamotrigine, which carries a black box warning for development of HLH as of April 2018. Patient met diagnostic criteria for HLH with hemophagocytosis, two cytopenias, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, acute hepatitis, and elevated interleukin-2 receptor.
Discussion: HLH is a rare hematological syndrome characterized by excessive activation of the immune system. The initial, nonspecific symptoms and potential of progressive multi-organ failure highlights the importance of early diagnosis. This interesting case illustrates the importance of reviewing a patients’ medication list in the setting of an acute illness, even when a syndrome as rare and severe as HLH is suspected. The initial workup for HLH typically includes infectious, malignant, autoimmune, and rheumatologic processes, but this case suggests a thorough medication history. This case also highlights the importance of establishing a diagnosis of HLH and promptly initiating treatment when clinical suspicion is high. Although this clinical syndrome typically presents with nonspecific symptoms, the presence of a constellation of clinical findings suggestive of excessive immune system activation can lead to an earlier diagnosis.
Conclusions: A thorough medication reconciliation is essential for all patients admitted to a hospital medicine service. In this case, a newly prescribed medication was the cause of a life-threatening disease with multi-organ failure.