Case Presentation: A 68 year old man with past medical history of rheumatoid arthritis with recent travel to Mexico was admitted after clinically worsening at home roughly a week after a previous 10 day admission for intermittent high fevers. The patient had had a prostate biopsy 2 weeks prior to his first admission and he claimed that that is when “all the trouble began.” He had presented previously with jaundice and complaining of high fevers. The patient had had an extensive workup including serological testing, repeated negative blood cultures, a negative TTE, and an abdominal CT that showed no intra-abdominal abscesses though showed hepatosplenomegaly. He was treated empirically with broad-spectrum antibiotics which were subsequently discontinued due to concern for drug fever. At discharge, he was given a presumed diagnosis of Felty syndrome due to his history of rheumatoid arthritis. Upon admission to our institution for FUO, he had no appreciable lymphadenopathy and his complete repeat infectious workup was negative including HIV, HCV, EBV, and CMV. He had a normal chemistry panel, mildly elevated transaminases, slight thrombocytopenia with platelet count of 130 and a normocytic anemia (Hgb 8.9), but with leukocytes within normal limits at 5.5. He underwent an abdominal ultrasound and abdominal MRI, which revealed liver hemangiomas and splenomegaly. A peripheral smear was obtained due to the patient’s history of international travel, which ruled out malaria, but incidentally showed atypical lymphocytes that were identified to be Diffuse Large B-cell Lymphoma on subsequent flow cytometry and bone marrow biopsy. The patient began appropriate chemotherapy treatment to which he has responded well.

Discussion: Fever of unknown origin (FUO) is a fever higher than 38.3 degrees celsius persisting for more than three weeks without an obvious source despite a comprehensive and step-wise investigation. The workup for FUO includes many serological studies including standard labs and blood cultures as well as basic imaging studies but does not include/specify a peripheral smear. While a complete blood count (CBC) with a differential has the potential to identify atypical cell types and quantities, it is not equivalent to a peripheral smear that has been reviewed by a trained pathologist. Etiology of FUO is roughly infectious 30%, connective tissue diseases 30%, neoplasms 20%, and other causes 20% of the time.

Conclusions: Our case demonstrates the importance of avoiding anchoring and premature closure. Hospitalists may feel in similar cases compelled to find an infectious source based on patient history, however, FUO is infectious only 30% of the time. It is our belief that the incorporation of a peripheral smear into the FUO workup, as opposed to solely a CBC with a differential, is a high value, low cost test that has the potential to diagnose the cause of fever, prevent further unnecessary testing, and expedite appropriate treatment.