S5380 Fever of Unknown Origin With Severe Hepatosplenomegaly in an Immunocompetent Woman

Introduction: Disseminated histoplasmosis is a rare fungal infection that can present with non-specific symptoms, making the diagnosis challenging. We report a case of 46-year-old woman presenting with hepatosplenomegaly and undergoing workup for fever of unknown origin. Case Description/Methods: A 46-year-old woman with diabetes mellitus who lives in the New England area was admitted for influenza pneumonia. She had a prolonged hospital course complicated by 8 weeks of recurrent fever (100-103°F) despite continuous, uninterrupted broad-spectrum antibiotics coverage. She was HIV negative and had multiple negative infectious workups. Physical examination was unremarkable and labs were only significant for a normocytic anemia (Hb 8.7 g/dL). Computed tomography (CT) abdomen and pelvis revealed severe hepatosplenomegaly (HSM) with no focal lesions. CT thorax with contrast showed left lower lobe and upper lobe bronchial inflammation, and reactive mediastinal lymphadenopathy but no evidence of pulmonary emboli. Rheumatological workup, bone marrow biopsy, and liver biopsy were all negative. Further infectious disease investigation excluded viral hepatitis, Epstein-Barr virus or cytomegalovirus infection, and tick-borne illness. Interestingly, the urine histoplasmosis antigen returned strongly positive while the serum histoplasmosis antigen and antibody were negative. Disseminated histoplasmosis was diagnosed based on positive urine antigen and exclusion of other causes. The patient was started on liposomal amphotericin B and her fever resolved within 3 days of treatment. She was switched to oral itraconazole therapy after 2 weeks and there has been no recurrence of fever. A retrospective history review identified a recent endemic outbreak of histoplasmosis in her living area due to construction activities. Discussion: We presented an extremely rare case of disseminated histoplasmosis characterized by fever of unknown origin and HSM without significant pulmonary involvement. Our case also featured the discordance between serum and urine histoplasmosis antigen, which accounts for only 2% of cases reported in the literature. Urine histoplasma antigen has a high sensitivity of 94%. Activities that disturb the soil and bird droppings is the major environmental risk factor in patients from non-endemic areas. Clinicians should have high suspicion for histoplasmosis in patients with both fever of unknown origin and HSM. Thorough history-taking should include exposure to soil and bird droppings.