Case Presentation: An 18-year-old male with no significant past medical history presented with four days of worsening fever, sore throat, nausea, vomiting, headache, and difficulty swallowing. One month prior, he presented to an urgent care with an enlarged tender lump below his chin and swollen lymph nodes. He was diagnosed with infectious mononucleosis (IM) and discharged with prednisone 20mg for five days followed by a two-day taper. The patient was evaluated at an ED two days prior to his current presentation and diagnosed with viral pharyngitis. He declined strep and monospot testing.On the day of admission, the patient presented to an ED and was found to be febrile at 103 F, tachycardic to 135 bpm, and had a positive monospot test. ED work-up was notable for WBC count (500/μL), hemoglobin (8.8 g/dL), ANC (10/μL), and platelet count (6000/μL), prompting transfer to our ED for admission. The patient was hyponatremic (Na of 131 mmol/L) likely due to poor intake and had acute kidney injury (Cr of 1.4 mg/dL), but no transaminitis. He was positive for both EBV IgM and IgG. Adenovirus, COVID, CMV, Hep B, Hep C, HIV, strep, direct antiglobulin test, paroxysmal nocturnal hemoglobinuria, histoplasma, and blastomyces testing were negative. Abdominal ultrasound showed no hepatosplenomegaly. Chest X-Ray was unremarkable. The patient was started on cefepime and later switched to levofloxacin, fluconazole, and acyclovir for neutropenic fever prophylaxis. Immune thrombocytopenia was unlikely as platelet count was not affected by dexamethasone 40 mg daily for four days but did improve with two irradiated units of platelets. He received several days of Neupogen, a G-CSF agonist, and Promacta, an EPO agonist, to stimulate bone marrow recovery. Prolonged pancytopenia prompted bone marrow biopsy which revealed hypocellular bone marrow with trilineage hypoplasia, negative for a hematolymphoid neoplasm. These findings may also indicate marrow recovery following an aplastic anemia associated with Epstein-Barr virus (EBV). CT of head/neck was performed on day five of admission due to dysphagia and neck pain to rule out neck abscess given leukopenia. Imaging revealed moderate swelling of the pharyngeal and palatine tonsils, likely secondary to IM, as well as possible bronchitis. This patient was diagnosed with EBV-IM resulting in a rare complication of severe pancytopenia and neutropenic fever. He was discharged after symptomatic improvement on Cyclosporine 200mg BID for 30 days and Promacta 150mg daily for 30 days for full recovery of blood counts and continued infection prophylaxis. He responded favorably and avoided the need for bone marrow transplant.

Discussion: Our findings demonstrate an unusual presentation of EBV-IM. Patients commonly have sore throat, fatigue, myalgias, and lymphadenopathy. Patients can experience splenomegaly, nausea, vomiting, palatal petechiae, and rash [3]. While mild neutropenia has been associated with EBV, pancytopenia is a rare presentation in immunocompetent patients with potentially fatal consequences [4-6]. Our patient presented with a severity of thrombocytopenia rarely seen with EBV bone marrow suppression.

Conclusions: Diagnosing EBV-IM can be complicated by presentations of pancytopenia and neutropenic fever. A thorough workup, as well as early detection and treatment are crucial to prevent superinfections and ensure a prompt recovery.