- 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 22%, 11%, and 23% of Western cases, respectively, and for 43%, 16%, and 23% 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. 28-1. 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. 18F-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 54% of cases. |
Treatment: 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.
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Prognosis: When no underlying source of FUO is identified after prolonged observation (>6 months), the prognosis is generally good.