Fever of Unknown Origin: A Rare Diagnosis Requiring High Suspicion

Fever is a classic reason for hospital visits, sometimes requiring admission. Its etiologies are numerous, ranging from simple and relatively common conditions to rare and complex pathologies, for which the differential diagnosis can present a true challenge for internists. A 78-year-old healthy female is referred to the emergency department due to marked fatigue for the past four months, with no other symptoms. Physical examination revealed fever, significant lower limb edema, and low blood pressure. Laboratory results revealed anemia and thrombocytopenia, associated with high ferritin and lactate dehydrogenase levels (1924 U/L and 1519 U/L, respectively) and mild hyponatremia (133 mEq/L). A thoracic-abdominal-pelvic CT scan showed only a splenomegaly of 17 cm without other significant findings. No microorganisms were found in multiple cultural samples, and fever persisted despite two courses of antibiotics. Viral serologies and zoonosis panel were negative. A bone marrow study was conducted to help explain the cytopenias, which revealed hemophagocytic cells, confirming the diagnosis of hemophagocytic syndrome. She started with systemic corticosteroid therapy, which improved her symptoms, and a few days later, it was confirmed a diffuse large B-cell lymphoma was the etiology. Because of its mostly unspecific manifestations, hemophagocytic syndrome requires a high degree of suspicion for timely diagnosis and treatment.