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A 59-year-old woman with epilepsy was admitted to hospital with a 6-year history of fever of unknown origin (FUO). Computed tomography (CT) showed extensive low-attenuation mesenteric and retroperitoneal lymphadenopathy. Investigations for malignancy and infection were negative, including two separate excisional biopsies of lymph nodes. An ascending aortic aneurysm was seen on CT, and a diagnosis of large vessel vasculitis (LVV) was considered. A trial of prednisone for presumed LVV was initiated and then discontinued when positron emission tomography (PET) failed to show vasculitis. Repeat core biopsy of a mesenteric lymph node revealed non-necrotizing granulomatous inflammation and histiocytes with periodic acid–Schiff (PAS)-positive intracellular material. Electron microscopy and polymerase chain reaction (PCR) of the tissue confirmed Tropheryma whipplei. She was treated with ceftriaxone for 2 weeks, followed by long-term combination doxycycline and hydroxychloroquine. The patient's seizure control improved on therapy, raising the suspicion that the seizure disorder was due to Whipple's disease.

An atypical case of Whipple’s disease presenting as fever of unknown origin: A brief review