Fever of Unknown Origin

Etiology:FUO is more commonly caused by an atypical presentation of a common disease than by a very rare disease. The most common causes of FUO can be categorized as infections, neoplasms, or noninfectious inflammatory diseases (NIIDs; e.g., “collagen or rheumatic diseases,” vasculitis syndromes, and granulomatous disorders). The frequency of each category differs between Western countries and countries in other parts of the world: infections, neoplasms, and NIIDs account for 19%, 12%, and 24% of Western cases, respectively, and for 43%, 20%, and 14% of cases in other geographic regions.
- Atypical presentations of endocarditis, diverticulitis, vertebral osteomyelitis, and extrapulmonary tuberculosis represent the more common infectious-disease diagnoses.
- The most common NIIDs that result in FUO are large-vessel vasculitis, polymyalgia rheumatica, sarcoidosis, familial Mediterranean fever, and adult-onset Still's disease.
- Among the neoplasms, malignant lymphoma is by far the most common cause of FUO. Fever occasionally precedes lymphadenopathy detectable by physical examination.

APPROACH TO THE PATIENT
FUO A structured approach to the pt with FUO is shown in Fig. 30-1. Structured Approach to Pts with Fever of Unknown Origin (FUO). The most important step in the diagnostic workup is the search for potentially diagnostic clues (PDCs) through complete and repeated history taking and physical examination. ¹⁸ F-fluorodeoxyglucose positron emission tomography combined with low-dose CT (FDG-PET/CT) can be used to guide additional diagnostic tests (e.g., targeted biopsies and culture) and aids in final diagnosis of FUO in ∼50% of cases.


FUO Empirical therapeutic trials with antibiotics, glucocorticoids, or antituberculous agents should be avoided in FUO except when a pt's condition is rapidly deteriorating after diagnostic tests have failed to provide a definitive result. Hemodynamic instability and neutropenia may prompt earlier empirical anti-infective therapies. Use of glucocorticoids and NSAIDs should be avoided unless infection and malignant lymphoma have been largely ruled out and unless inflammatory disease is both probable and debilitating or life-threatening. Anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, blocks the activity of both IL-1α and IL-1β and is extremely effective in the treatment of many autoinflammatory syndromes. A therapeutic trial with anakinra can be considered in pts whose FUO has not been diagnosed after later-stage diagnostic tests.

Prognosis: When no underlying source of FUO is identified after prolonged observation (>6 months), the prognosis is generally good.