Fever of Unknown Origin in a Young Woman With Multiple Comorbidities: A Diagnostic Challenge

Fever of unknown origin (FUO) presents a diagnostic challenge, requiring detailed evaluation of infectious, autoimmune, inflammatory, and neoplastic causes. We report the case of a 28-year-old female patient with a history of polycystic ovary syndrome, pituitary microadenoma, and prior thromboembolic events, who presented with two months of persistent fever, abdominal pain, and diarrhea. The patient recently traveled to Europe and reported freshwater swimming and walking barefoot on beaches. Initial imaging showed multifocal hepatic abscesses and colitis which prompted empiric antimicrobial therapy which showed minimal improvement. Extensive infectious workup, including malaria, HIV, viral hepatitis, and parasitic testing, was negative. In terms of laboratory evaluation, the patient's complement C3 was elevated (176 mg/dL), C4 was normal (29 mg/dL), and ANA, p-ANCA, and c-ANCA were negative. Karius testing detected HHV-7 and parvovirus B19 exposure, with equivocal Brucella IgM. Liver biopsy demonstrated non-necrotizing granulomas and abscesses, but cultures were negative. The patient ultimately responded well to therapy with corticosteroids with her fever resolving and showing signs of significant clinical improvement. This case presentation highlights the rarity of lupus-associated granulomatous hepatitis as FUO showing the importance of considering autoimmune diseases in the differential diagnosis and utilizing liver biopsy to uncover uncommon etiologies.