After the initial evaluation, it is often necessary to reassess the patient to ascertain the evolution of the fever and the emergence of new symptoms or physical signs. Additional laboratory tests should be performed. The clinician should give consideration to thyroid function testing. Other endocrinologic causes of fever, including adrenal insufficiency; and pheochromocytoma, should be sought out if the history, vital signs, or serum electrolytes are suggestive. Multiple myeloma can manifest subtly with fever, and serum protein and urine protein electrophoresis might be worthwhile. Tooth abscesses can be occult, and teeth radiographs may be revealing. If TEE has not been performed, it should be considered. Additionally, if cross-sectional imaging has already been performed and found to be unrevealing, one should consider performing a nuclear medicine study in an attempt to locate a region of inflammation. This may be useful early in the course of work-up. Lower extremity ultrasonography to examine the deep leg veins is revealing in some cases.
Both rheumatologic and infectious serologies can occasionally be illuminating. DeKleijn et al found diagnostic utility in determining serum mixed cryoglobulins during the reevaluation for an FUO. Other tests may provide additional clues to rheumatologic diseases, such as systemic lupus erythematosus and vasculitis. These include the antineutrophil cytoplasmic antibody, serum complements (C3, C4, and CH50), anti-double-stranded DNA. Additional serologic testing to evaluate for infectious causes might include hepatitis antibodies, antistreptolysin О antibody, and antibodies against Coxiella burnettii and Brucella, Borrelia, or Bartonella species. Mycoplasma species and Chlamydia psittaci rarely cause a culture-negative endocarditis, and serologic studies for these organisms may be helpful.
Consideration should also be given to bone marrow biopsy. This could have significant utility in discovering occult malignancy or infection, and biopsy proves more useful than aspirate. Cultures taken alone have little diagnostic yield.
In the absence of additional clues, colonoscopy, liver biopsy, and, in patients older than 55 years of age, temporal artery biopsy may be helpful. Colonoscopy or sigmoidoscopy can provide biopsy samples for histology as well as bacterial, mycobacterial, and fungal cultures and can screen for occult colon malignancy. Since symptoms of temporal arteritis can be subtle, and the erythrocyte sedimentation rate need not be elevated, blind temporal biopsy has been shown to have diagnostic utility.
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