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69333.pdf (publisher's version ) (Closed access)Nowadays, fever of unknown origin (FUO) is generally defined as a fever higher than 38-3 degrees C lasting for a period of at least three weeks, in which no definitive diagnosis has been made after a number of obligatory tests. A diagnostic algorithm is proposed in which history taking, physical examination and the obligatory tests are the most important steps in the search for potentially diagnostic clues (PDCs). Next, factitious fever and drug fever should be ruled out. Further diagnostic procedures should be guided by the PDCs. If this does not lead to diagnosis or if there are no useful PDCs, further screening, including 18F-fluorodeoxyglucose positron emission tomography, should be performed. In 30 to 50% of the patients with FUO no diagnosis can be reached. If their clinical condition is stable, waiting to see if new PDCs develop is recommended. Most patients in whom no diagnosis can be made, have a good prognosis. Supportive treatment with NSAIDs can be helpful. Only if patients deteriorate, should other therapeutic trials be considered