Ehrlichia chaffeensis-associated Hemophagocytic Lymphohistiocytosis: A Case Series and Literature Review

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon condition characterized by abnormal, excessive immune activation resulting in severe cytopenias from an uncontrolled inflammatory response. It can be primary/ familial or secondary/sporadic. Infections, particularly viral infections are a common cause of secondary HLH. HLH due to Human monocytic ehrlichiosis (HME) is very rare, hence we are reporting our cases. Objective: To review cases of Ehrlichia-associated HLH at our institution and perform a literature review regarding this entity. Methods: We reviewed cases of Ehrlichia-associated HLH for the previous two years at our institution (Carilion Clinic). We then performed a review of the published literature on it, using Pubmed. Results: Over the past two years, five cases of Ehrlichia-associated HLH were diagnosed at our hospital. The average age of the patients was 67 years with predominantly males. All the patients were pancytopenic, and a majority had abnormal liver function tests. Diagnosis of ehrlichiosis was made by serum polymerase chain reaction (PCR) assay on blood. Patients had further testing done because of lack of clinical improvement. All patients had significantly elevated ferritin levels. Bone marrow biopsy samples of all patients showed findings of hemophagocytosis. All, but one, patients were treated with doxycycline and a combination of etoposide and dexamethasone. Three patients recovered while two died. On review of medical literature, we found a total of only 36 cases of Ehrlichia-associated HLH, including our five cases. There were 19 adults and 17 children. Both population groups showed varying degrees of pancytopenia. Splenomegaly was relatively uncommon, seen in less than one-third of the patients. Ferritin and triglyceride levels were routinely elevated. Bone marrow biopsy showing hemophagocytosis was the confirmatory test in all patients. A significant number of patients, both adults and children, required a combination of doxycycline and chemotherapy (etoposide and dexamethasone) to achieve clinical cure. Children had a better prognosis than adults, with one child and four adults succumbing to their illness. Conclusions: Ehrlichia-associated HLH is a rare but emerging disease entity. In endemic areas, a high degree of suspicion is required to diagnose ehrlichiosis and HLH resulting from it. Early diagnosis and prompt initiation of treatment for HLH is key to a favorable outcome.