Case Presentation: A 54-year old Caucasian man, with no significant past medical history presented to the Emergency Department with complaints of fever to 38.9°C, chills, night sweats and mild diffuse headaches which had progressed over the prior 5 days. Recent travel history included a trip to Puerto Vallarta 2 months prior to presentation. While on vacation the patient recalled getting mosquito bites and participation in water activities. He is a resident of East Altadena, CA. He denied any sick contacts and had no exposure to animals other than his pet dog. On presentation he was alert, oriented and in no acute distress. Physical exam was significant for hepatosplenomegaly and a maculopapular rash noted on the torso and thighs, which resolved later that day. Initial lab results were significant for thrombocytopenia (platelet count of 43k) and transaminitis (AST 260 and ALT 211). The patient was admitted and started on broad spectrum antibiotics. His hospital course was complicated by the onset of ARDS on day 2, which responded to supportive measures and BiPAP. Because he met 5 out of the 8 diagnostic criteria for HLH, including fever >38.5°C, splenomegaly, cytopenia (anemia and thrombocytopenia), ferritin level of 8,149, elevated IL2α, on day 3 he was started on oral Dexamethasone (per HLH-94 protocol). A bone marrow biopsy was done on day 6, which revealed Chronic Lymphocytic Leukemia without significant hemophagocytosis. During the dexamethasone taper, there was complete resolution of all symptoms and the patient was discharged home in stable condition on day 12. Labs ultimately revealed elevated titers for; EBV IgG, Mycoplasma IgM and Murine Typhus IgM. In addition to the patient’s occult malignancy these are also recognized potential HLH triggers.
Discussion: We identified multiple potential triggers for HLH in an adult. Our patient met 5 of the 8 HLH diagnostic criteria, intended for use in the pediatric population. If the diagnosis is suspected and 5 or more criteria are met, initiating treatment is advised. Of note, our differential diagnosis included Macrophage Activation Syndrome with features of HLH and Adult Onset Still’s Disease. This case also highlights the utility of the HLH-94 protocol with Dexamethasone in the prompt treatment of these patients. Given that the patient’s condition had improved while on Dexamethasone, Etanercept (from the HLH-94 protocol) was not started. HLH is a clinical diagnosis and not all criteria should be met before initiating treatment. Early recognition can potentially improve survival outcomes, as we have seen in this case.
Conclusions: Hemophagocytic lymphohistiocytosis (HLH) is a rare, rapidly progressive and potentially life-threatening syndrome of excessive immune system activation with subsequent hypercytokinemia. It is known to primarily affect the pediatric population and can be triggered by events that disrupt immune homeostasis, such as infection. Prompt diagnosis can facilitate early initiation of treatment and prevent potential multi-organ failure and morbidity.