Case Presentation: A 59-year-old female with medical history significant for depression/anxiety, CAD, hypothyroidism, and tobacco use, recently admitted for leukopenia and normocytic anemia thought to be secondary to Epstein Barr Virus (EBV), Parvovirus, and adverse drug event from cefdinir use, presents with persistent fatigue and weight loss to an outside hospital. She was noted to have pancytopenia with 3% blasts on a peripheral blood smear. With concern for a hematologic malignancy, she was transferred to our institution. On admission, the patient had pancytopenia, hypofibrinogenemia, elevated LDH, and significantly elevated ferritin. A cytokine panel demonstrated significant elevations, particularly soluble IL2 receptor (sCD25). Infectious workup revealed a positive EBV IgG and EBV PCR of 84,684 IU/mL (Table 1). Per hematology, with concern for myelodysplastic syndrome (MDS), a bone marrow biopsy was obtained and revealed 20-30% cellularity with trilineage hematopoiesis, mild-moderate erythroid and megakaryocytic dyspoiesis, no increase in blasts, and mild increase in polytypic plasma cells. Rheumatologic workup for autoimmune vasculitis yielded positive PR3, MPO, p-ANCA, and ANA, with hypocomplementemia. The patient was diagnosed with hemophagocytic lymphohistiocytosis (HLH) secondary to EBV infection. She was treated with IV steroids and ganciclovir. The patient also developed altered mental status from HLH, so received intrathecal methotrexate. Upon discharge, the patient’s EBV PCR was undetectable, blood counts stabilized, and she overall clinically improved. She followed closely as an outpatient with hematology.
Discussion: HLH is a disorder of cytotoxic T lymphocyte, natural killer cell, and macrophage overactivation that results in increased cytokine release. This process causes consumption of red blood cells and platelets, as well as immune-mediated injury to multiple organ systems (1). HLH can have primary causes from genetic mutations or secondary causes from malignancy, infections, or autoimmune diseases. Criteria for HLH clinical diagnosis includes five of eight of the following: fever, splenomegaly, cytopenia, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis on tissue biopsy, low NK cell activity, significantly elevated ferritin, and elevated sCD25 (2). Specifically for HLH secondary to infection, EBV has been found to be the most likely cause. Treatment guidelines entail a short course of corticosteroids (3). If concerned for CNS involvement of HLH, intrathecal chemotherapy is indicated (4).
Conclusions: This case demonstrates how HLH can manifest abstractly in patients with EBV infection and is essential to consider, though rare. While our patient was presenting with nonspecific symptoms resulting in a wide differential concerning for infectious, hematologic, and autoimmune etiologies, it is important to identify the criteria to clinically diagnose patients with HLH and treat appropriately with aggressive management to prevent poor outcomes.
