Case Presentation: We present a 70-year-old female with a past medical history of heart failure, atrial fibrillation, COPD, and type-2 diabetes mellitus who was admitted with subjective fevers, vomiting, diarrhea, and intermittent cough for five days. On admission, the patient was alert and oriented but febrile (39C) and tachycardic (112 beats/min). Laboratory tests were significant for leukopenia (1.8 x 103/μL), thrombocytopenia (58 x103/μL), hyponatremia (128 mmol/L), hypercreatininemia (1.38 mg/dL), elevated aspartate aminotransferase (101 U/L) and lactic acid (1.8 mmol/L). She became progressively somnolent with shock physiology, leading to vasopressor initiation. Family discussions revealed that the patient was employed at a campground, raising concern for zoonotic illnesses. Tick-borne disease and arbovirus laboratory panels were ordered, and antibiotics (meropenem and doxycycline) were initiated. Follow-up laboratory studies showed lymphocytosis, elevated proteins in CSF, serum pancytopenia, and bone marrow suppression on peripheral blood smear. Increasing concern for HLH elicited a bone marrow biopsy, and steroids were started. On day 10, negative tick-borne panel antibody results and enduring encephalopathy prompted the discontinuation of doxycycline and the patient’s transfer to a tertiary medical center for the management of suspected HLH. Due to clinical improvement, steroids were discontinued, and chemotherapy was held while awaiting bone marrow biopsy and CD25 results. Results from the outside hospital laboratory department yielded a negative bone marrow biopsy, monocytosis, positive E. Chaffeensis polymerase chain reaction (PCR) results, and elevated CD25 values. The patient was restarted on a 7-day course of oral doxycycline for the treatment of ehrlichiosis.

Discussion: This case reinforces the importance of temporal considerations of diagnostics. While indirect immunofluorescence antibody (IFA) testing is the gold standard for definitive diagnosis of HME, it can take weeks for a significant rise in antibody titers. PCR testing is most sensitive in the acute stages of illness. This patient’s negative HME antibody results in their first week of illness, non-specific clinical symptoms, and pancytopenia increased suspicions for HLH secondary to an infection or leukemic disease, similar to previous rare cases reported in the literature. Despite an H-score of 177 and meeting 5 out of 9 diagnostic criteria for HLH (elevated ferritin and CD25, hypertriglyceridemia, peripheral blood cytopenias, and fever), negative bone marrow biopsy results and rapid clinical improvement eliminated the need for chemotherapy. Ultimately, positive HME-specific PCR results facilitated appropriate antibiotic treatment and full recovery.

Conclusions: Human monocytic ehrlichiosis (HME) has become increasingly endemic in the northeastern and midwestern United States. Non-specific clinical symptoms such as fever, headache, myalgias, nausea, vomiting, and rash usually present 7-14 days after exposure to a Lone Star tick, making HME challenging to diagnose. This case report presents HME in an elderly patient with negative antibody testing for tick-borne illness. Suspicion for leukemic disease or hemophagocytic lymphohistiocytosis (HLH) coupled with deferred reporting of PCR results after transfer to a tertiary care center delayed diagnosis and treatment.