Fever of Unknown Origin: Focused Diagnostic Approach Based on Clinical Clues from the History, Physical Examination, and Laboratory Tests
Section snippets
Fever of unknown origin: classic and current causes
FUOs fall into four general categories. The relative frequency of the causes of FUO in each category is the basis for a phased diagnostic approach. Phase I of an FUO evaluation consists of a FUO relevant history, physical examination, and nonspecific laboratory tests. The phase I evaluation provides the basis for determining the course of the FUO work-up. Features in the history, physical findings, and laboratory abnormalities in the initial FUO evaluation suggest which general category of
Overview
After the initial FUO-relevant evaluation most of the common causes of FUOs in each category may be readily diagnosed. Combining the relevant FUO features on physical examination with selected nonspecific laboratory test abnormalities limits diagnostic possibilities and eliminates other causes from further diagnostic consideration. The diagnostic significance of selected nonspecific tests cannot be overemphasized. The clinical significance of nonspecific laboratory abnormalities is enhanced
Fever of unknown origin: diagnostic usefulness of the Naprosyn test
The Naprosyn test was first developed by Chang [32], an oncologist. Using Naprosyn (naproxen) over a 3-day period (375 mg orally twice daily) he was able to differentiate neoplastic from infectious FUOs. The Naprosyn test is considered positive when there is a rapid or sustained defervescence during the 3 days of the test period. Fever in patients with neoplastic disorders recurs after cessation of the Naprosyn test. Those with infectious diseases undergo little or no drop in their temperatures
Fever of unknown origin: definitive evaluation
Definitive diagnostic testing is done in the third or final phase of diagnostic FUO evaluation. In patients with an appropriate epidemiologic history, serologic tests for visceral leishmaniasis should be obtained. Most infectious, rheumatic-inflammatory, neoplastic, and miscellaneous disorders should be diagnosed after an initial and focused diagnostic FUO evaluation. The disorders not diagnosed to this point are uncommon causes of FUO and require special testing or tissue biopsy for diagnosis
Liver biopsy
If there are signs and symptoms in a presenting FUO syndrome complex that suggest liver involvement, then liver biopsy may be diagnostically helpful. Liver biopsy is most useful in granulomatous hepatitis where the differential diagnosis may be useful in differentiating granulomas caused by infections, rheumatic-inflammatory disorders, or neoplastic causes. A liver biopsy may be useful in diagnosing suspected miliary tuberculosis as a cause of FUO [4], [39].
Lymph node biopsy
Lymph node biopsy is most useful to
Fever of unknown origin: approach to undiagnosed and recurrent disorders after a focused evaluation
Even some rare disorders may be potentially diagnosed during the initial and focused FUO evaluation. The serum protein electrophoresis may suggest otherwise unsuspected sarcoidosis, hyperimmunoglobulinemia D syndrome, or Schnitzler's syndrome. The serum protein electrophoresis with increase in IgD accompanied by a decrease in IgA should suggest hyperimmunoglobulinemia D syndrome. Schnitzler's syndrome is suggested by a monoclonal increase in IgM antibodies. Polyclonal gammopathy seen on the
Summary
FUOs usually are limited by their progression and are self-terminating or are terminated with effective therapy. Some causes of FUO are prone to recurrence. In the main, recurrent FUOs are most often caused by rheumatic-inflammatory etiologies. Patients with infectious FUOs usually resolve with or without therapy in less than a year. Neoplastic disorders usually present themselves in less than 1 year but some disorders may recur episodically over a prolonged period of time (eg, preleukemias,
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