A Fatal Case of Hemophagocytic Lymphohistiocytosis Triggered By Babesiosis

Introduction:

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by hyperactivation of macrophages and T lymphocytes. While HLH is primarily inherited in a recessive manner among children, in adults, it is more commonly associated with underlying infections, autoimmune disorders, and malignancies. However, the association between HLH and Babesia infection remains exceptionally uncommon, with only a few reported cases in the medical literature. In this report, we present a unique case of HLH in the context of babesiosis, shedding light on the crucial clinical features and risk factors. By raising awareness of this rare differential diagnosis, we aim to contribute to early recognition and timely treatment, potentially reducing mortality from this treatable illness.

Case Presentation:

A 77-year-old male with history of deep vein thrombosis (DVT), Parkinson's disease, and lumbar radiculopathy on chronic prednisone, presented for progressive generalized weakness, leg pain, and confusion. Initial labs showed normocytic anemia, thrombocytopenia, low fibrinogen and elevated INR and liver enzymes (Table 1). Multiple ischemic signs were noted including acute on chronic DVT, as well as findings of marked splenomegaly with wedge infarcts and periportal lymphadenopathy on abdominal ultrasound and CT (Figure 1). The underlying etiology of these findings was unclear and broad differential work up was pursued. Given the anemia and thrombocytopenia on presentation, the patient received multiple blood products including platelets, red blood cells, fresh frozen plasma and cryoprecipitate, in addition to vitamin K. No schistocytes were seen peripherally, and DIC/TTP workup was negative. Multidisciplinary teams evaluated the risk versus benefit of anticoagulation with heparin drip considering evidence of multi-organ ischemic damage. It was briefly initiated, but later held due to persistent thrombocytopenia and abnormal liver function. Further work up only revealed hemolysis with a low haptoglobin and elevated LDH (Table 1). However, the follow up Coombs test was negative, ruling out immune mediated hemolysis. While symptomatic management continued, blood parasite screen obtained on admission indicated Babesia microti infection. Upon repeat testing, no evidence of babesia was identified on labs or blood smear. However, this finding was skewed by the multiple transfusions the patient received. Unfortunately, the clinical course rapidly declined, and the patient's family elected a transition to comfort care measures whereby the patient expired within two days of presentation. Remaining work up resulted posthumously, with CD25 levels elevated at 38,354.0 pg/mL. Coupled with the previously established splenomegaly, pancytopenia, hypertriglyceridemia, and elevated ferritin, these findings indicate a diagnosis of HLH, likely triggered by Babesia microti infection.

Conclusion:

HLH should be strongly suspected in patients from endemic regions, especially with additional risk factors such as age, genetics, and immunosuppression. Tools such as the HScore and the HLH-2004 criteria can aid in further patient risk stratification. Urgent treatment with steroids and addressing underlying babesiosis with atovaquone, azithromycin, and potentially red blood cell exchange transfusion, remains crucial for preventing decompensation and improving outcomes.