Chapter 019. Fever of Unknown Origin
(Part 4)

Specialized Diagnostic Studies
Classic FUO
A stepwise flow chart depicting the diagnostic workup and therapeutic
management of FUO is provided in Fig. 19-1. In this flow chart, reference is made
to "potentially diagnostic clues," as outlined by de Kleijn and colleagues; these
clues may be key findings in the history (e.g., travel), localizing signs, or key
symptoms. Certain specific diagnostic maneuvers become critical in dealing with
prolonged fevers. If factitious fever is suspected, electronic thermometers should
be used, temperature-taking should be supervised, and simultaneous urine and
body temperatures should be measured. Thick blood smears should be examined
for Plasmodium; thin blood smears, prepared with proper technique and quality
stains and subjected to expert microscopy, should be used to speciate Plasmodium
and to identify Babesia, Trypanosoma, Leishmania, Rickettsia, and Borrelia. Any
tissue removed during prior relevant surgery should be reexamined; slides should
be requested, and, if need be, paraffin blocks of fixed pathologic material should
be reexamined and additional special studies performed. Relevant x-rays should be
reexamined; reviewing of prior radiologic reports may be insufficient. Serum
should be set aside in the laboratory as soon as possible and retained for future
examination for rising antibody titers.
Figure 19-1

Approach to the patient with classic FUO.
a
"Potentially diagnostic
clues," as outlined by de Kleijn and colleagues (1997, Part II), may be key
findings in the history, localizing signs, or key symptoms. ANA, antinuclear
antibody; CBC, complete blood count; CMV, cytomegalovirus; CRP, C-reactive
protein; CT, computed tomography; Diff, differential; EBV, Epstein-Barr virus;

reaction (PCR) to amplify and detect viral nucleic acid (Chap. 172). A recent
report described a highly multiplexed oligonucleotide microarray using PCR
amplification and containing probes for all recognized vertebrate virus species and
for 135 bacterial, 73 fungal, and 63 parasitic genera and species. The eventual
clinical validation of such microarrays will further diminish rates of undiagnosed
FUO of infectious etiology.