In human medicine, fever of unknown origin (FUO) is defined as pyrexia of greater than two to three weeks duration (i.e. sufficient time for self-limiting infections to resolve) during which repeat physical examinations and standard diagnostic testing have failed to reveal an underlying cause. Additional criteria are also occasionally suggested, such as presence of non-specific signs of illness, or hospitalization to ensure patient compliance with antibiotic administration. Similar specific criteria have not been accepted by veterinary internists; however, using similar guidelines, most internists will define patients as having a fever of unknown origin if pyrexia persists beyond one to two weeks, physical examination prior to referral does not reveal any abnormalities, and the minimum data base fails to localize an underlying disease process to a particular organ system.
In theory, any inflammatory disease, including infectious, immune-mediated, and neoplastic diseases, may stimulate sufficient tumor necrosis factor-α and interleukin-1 and -6 production to result in persistent fevers. However, diseases which result in the official diagnosis of FUO are typically indolent, slowly progressive, or relatively occult. Two retrospective studies, published ten years apart, have reviewed the final diagnoses ultimately made in dogs referred to veterinary teaching hospitals for fever of unknown origin using approximately the same criteria as those mentioned above. Selected results in these populations of dogs included:
It is important to mention that both of these studies were performed in the United Kingdom, so the relative prevalence of various infectious diseases would be expected to alter results of similar studies in the United States; in truth, results from different sites even within North America would likely vary widely as well. Nevertheless, despite the variation in time and geography between these sites and the dog and cat populations most of the audience members here evaluate, it is clear that when a diagnosis can be made, the most likely causes of fever of unknown origin are most likely immune mediated diseases (with joint and CNS diseases predominating) or infectious diseases (with no single occult site of infection being more likely. Neoplasia accounts for less than 10% of fever of unknown origin, with leukemia being most likely.