Fever of unknown origin (FUO) refers to the presence of a documented fever for a specified time, for which a cause has not been found after a basic medical evaluation. The classic criteria developed in 1961 included: temperature greater than 101°F (38.3°C), for at least three weeks, and inability to find a cause after one week of study. Within the past decade, a revision has been proposed that categorizes FUO into classic, hospital acquired FUO, FUO associated with low white blood counts, and HIV associated FUO (AIDS related). The most frequent cause of FUO is still infection, though the percentage has decreased in recent years. Tuberculosis remains an important cause, especially when it occurs outside the lungs. The decrease in infections as a cause of FUO is due in part to improved culture techniques. In addition, technological advances have made it easier to diagnose non-infectious causes. For example, tumors and autoimmune diseases in particular are now easier to diagnose. (An autoimmune disease is one that arises when the body tolerance for its own cell antigenic cell markers disappears.)
Few symptoms in medicine present such a diagnostic challenge as fever. Nonetheless, if a careful, logical, and thorough evaluation is performed, a diagnosis will be found in most cases. The patient’s past medical history as well as travel, social, and family history should be carefully searched for important clues.
Usually the first step is to search for an infectious cause. Skin and other screening tests for diseases such as tuberculosis, and examination of blood, urine, and stool, are generally indicated. Antibody levels to a number of infectious agents can be measured; if these are rising, they may point to an active infection.Various x-ray studies are also of value. In addition to standard examinations, recently developed radiological techniques using ultrasound, computed tomography scan (CT scan) and magnetic resonance imaging (MRI) scans are now available. These enable physicians to examine areas that were once accessible only through surgery. Furthermore, new studies using radioactive materials (nuclear medicine), can detect areas of infection and inflammation previously almost impossible to find, even with surgery.Biopsies of any suspicious areas found on an x-ray exam can be performed by either traditional or newer surgical techniques. Material obtained by biopsy is then examined by a pathologist to look for clues as to the cause of the fever. Evidence of infection, tumor or other diseases can be found in this way. Portions of the biopsy are also sent to the laboratory for culture in an attempt to grow and identify an infectious organism.Patients with HIV are an especially difficult problem, as they often suffer from many unusual infections. HIV itself is a potential cause of fever.
Tumor markers are not an accepted part of FUO workup. More recently, PET scan is being utilized to find the primary source of fever.
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