Referral of patients with fever of unknown origin to an expertise center has high diagnostic and therapeutic value

up to 50% of patients with fever of unknown origin (FUO) remain undiagnosed despite extensive evaluation. In expertise centers, at least 25-63% of these patients are referred after evaluation in another hospital. The diagnostic and therapeutic yields of referral to an expertise center are currently unknown.To determine the diagnostic and therapeutic yield of referral of patients with fever of unknown origin (FUO) that remain undiagnosed in non-expertise hospitals.Data on workup, outcome, treatment and prognosis were extracted from medical records of all 236 patients referred to the Radboud university medical center's department of internal medicine because of FUO between January 2005 and June 2014.A final diagnosis could be made in 110 of 192 tertiary referred FUO patients. The rate of diagnosis did not differ between patients referred for first opinion or after tertiary referral (68.2 vs. 57.3%, P = 0.234). Over half of undiagnosed tertiary referred patients were treated, and fever resolved in half of these patients. Of 96 undiagnosed patients, two died (2.1)% and in both death was considered unrelated to the febrile disease.The diagnostic rate in patients with FUO does not differ between patients that are tertiary referred and patients that have not been previously evaluated in another hospital. With a total diagnostic value of 57.3% and an additional therapeutic yield of 10.9% in undiagnosed patients, tertiary referral should therefore be considered in patients that remain undiagnosed in a non-expertise center.