Babesia induced cytokine storm: A rare cause of secondary hemophagocytic lymphohistiocytosis Free

Background: Hemophagocytic Lymphohistiocytosis (HLH) is characterized by overactivation of cytotoxic T lymphocytes, natural killer cells, and macrophages, which can induce a cytokine storm (Ponnatt et al., 2022). The specific pathogenesis of acquisition of secondary HLH is unclear, but common triggers of HLH include infection, malignancy, and autoimmune disorders. This rare disorder is usually fulminant in immunocompromised adults and can mimic several other diagnoses (Mahija et al., 2023). We present a rare case of non-fulminant HLH in the context of babesiosis in an immunocompetent patient.

Case Presentation: A 72-year-old male with a history of coronary artery disease and no significant family history presented to the emergency department with generalized fatigue, exertional weakness, and 7-pound unintentional weight loss. His symptoms began when he moved to the United States from Poland 3 months earlier. He noted a possible tick bite 3-4 weeks prior to his presentation to the emergency department. Besides fever, the physical exam was unremarkable, with no visible tick bites, rashes, hepatomegaly, or lymphadenopathy. Upon initial presentation his bloodwork was remarkable for triple lineage pancytopenia and transaminitis. Initially, this was thought to be a tick-borne illness such as anaplasmosis and doxycycline was empirically started. Further bloodwork found ferritin >7,500, triglycerides 294, and D-dimer 17.5. Splenomegaly identified on imaging raised concerns for HLH. Bone marrow aspirate findings of hemophagocytosis and elevated soluble IL-2 receptor alpha led to 6 of the 8 diagnostic criteria for HLH to be met. Treatment with Dexamethasone and Etoposide was initiated per HLH-94 guidelines (Henter et al., 2007). The workup to rule out central nervous system (CNS) involvement via lumbar puncture and MRI brain were negative. The tick panel was positive for Babesia, and antibiotics were switched to Azithromycin and Atovaquone. Antibiotics were extended for an additional 2 weeks after cultures for Babesia cleared.

Discussion: Delayed diagnosis and management of HLH can cause end-organ damage and death (Akel et al., 2017). This case exemplifies the need for broad differentials in patients with a history of tick exposure and pancytopenia. The lack of improvement of thrombocytopenia after 48 hours of antibiotics should raise suspicion for a secondary cause of pancytopenia. Early identification can prevent further spread including CNS spread and prevent the need for hematopoietic stem cell transplants. Screening tools like HScore distinguish hemophagocytic syndromes such as HLH from sepsis or acute hematologic malignancies, allowing for earlier HLH diagnosis and improved outcomes (Fardet et al., 2014).