Causes of FUO

The three major categories of causes of FUO--infections, collagen

vascular and granulomatous diseases, and tumors--remain unchanged
from the classic studies of Petersdorf and Beeson (1) (table 1)
!o"ever, the t#$es of diseases that are noted in these categories have
changed over the last %& #ears ('-() For e)am$le, s#stemic lu$us
er#thematosus, a common cause of FUO in the $ast, is no" more
easil# diagnosed b# serologic tests and rarel# *ualifies as an FUO
+iseases that "ere un,no"n or not "ell described several decades
ago, such as !-. and c#tomegalovirus (/0.) infections, are causes of
FUO toda# -n contrast, rheumatic fever has all but disa$$eared 0an#
diseases that $reviousl# caused FUO no longer attain this status
because of dramatic im$rovements in diagnostic imaging in the last
several decades
The causes of FUO differ among various $atient grou$s For e)am$le,
self-limited viral s#ndromes are an uncommon cause of FUO in older
adults, but tem$oral arteritis, tumors, and tuberculosis are more li,el#
in older $ersons than #ounger ones (1,1&) 2mong $ersons "ith !-.
infection, FUO is almost al"a#s due to an infectious cause (11) -n
addition, travelers ma# be e)$osed to unusual infectious agents that
the# carr# "ith them "hen the# return home, thus e)$anding the
differential diagnosis for FUO (1')
Infections
-nfections remain the most common cause of FUO, constituting about
a third of cases in various case series over the last five decades (3)
The infections noted most often are abscesses, endocarditis,
tuberculosis, and /0. infection (4-5) 2bscesses are diminishing in
im$ortance, because the# are discovered earlier in the "or,u$ for
fever, before the definition of FUO is met (6,5) 0ost cases of t#$ical
sta$h#lococcal or stre$tococcal endocarditis are easil# diagnosed FUO
is more li,el# to be encountered in $atients "ho have culture-negative
endocarditis due to ina$$ro$riate $rior antibiotic use or difficult-to-
culture organisms
Tuberculosis, although less common no" than half a centur# ago,
must al"a#s be considered as a cause of FUO 0iliar# and
e)tra$ulmonar# tuberculosis are the most li,el# forms to $resent as
FUO 7everal viral infections can $roduce $rolonged fevers and $resent
as FUO8 of these, /0. infection is the most common, but 9$stein-Barr
virus (9B.) and !-. infections are also causes of FUO
Tumors
Tumors have classicall# been the second most common cause of FUO
in adults (3) !o"ever, in recent re$orts, the# have accounted for onl#
5: to 14: of FUO cases (6,5) The routine use of com$uted
tomogra$h# (/T) has led to earlier diagnosis of man# tumors, and
the# are not as common a cause of FUO as the# once "ere
Tumors that $resent most often as FUO are hematologic malignancies,
es$eciall# !odg,in;s disease and other l#m$homas Pel-9bstein
fevers--those that occur dail# for da#s to "ee,s then disa$$ear, onl#
to rea$$ear later in the same $attern--are no" rarel# seen Other
hematologic malignancies, such as multi$le m#eloma and leu,emias,
are less common causes of FUO
2mong solid tumors, renal cell carcinoma is most often noted to cause
FUO8 much less commonl#, he$atomas and cancer of the colon and
gastrointestinal tract, lung, and breast can cause FUO 2trial m#)omas
are mentioned less fre*uentl# as enigmatic causes of fever, $robabl#
because of the earlier use of transeso$hageal echocardiogra$h# than
in the $ast
Collagen vascular diseases, granulomatous diseases
<ecent revie"s of FUO that have grou$ed collagen vascular diseases
and granulomatous diseases together have found this categor# to be a
more common cause of FUO than tumors (6,5) 7till;s disease is the
most fre*uent diagnosis in adults #ounger than %& #ears (4,%-5)8 in
older adults "ith FUO, tem$oral arteritis is the most common diagnosis
((,1) Other causes of FUO include $ol#arteritis nodosa,
cr#oglobulinemia, $ol#m#ositis, =egener;s granulomatosis, and
sarcoidosis -nflammator# bo"el disease ma# $resent as FUO "ith fe"
abdominal or gastrointestinal com$laints
Other causes of FUO
/ommon entities, such as $ulmonar# emboli and hematomas, can
manifest as FUO $rimaril# 0an# different drugs can cause fever (table
'), and h#$erth#roidism and th#roiditis can also $resent as FUO
Periodic fevers, such as familial 0editerranean fever, are rare and
occur in select $o$ulations Factitious and fraudulent fevers--
interesting diagnostic dilemmas that a$$ear in ever# series of FUO--
are uncommon8 the# occur almost entirel# in #oung "omen lin,ed to
the healthcare $rofession
Table 2. Commonly used medications that can cause fever of
unknown origin
ntimicrobial agents
/arba$enems
/e$halos$orins
0inoc#cline !/l
>itrofurantoin
Penicillins
<ifam$in
7ulfonamides
nticonvulsants
Barbiturates
/arbama?e$ine
Phen#toin
ntihistamines
Cardiovascular drugs
!#drala?ine !/l
Procainamide !/l
@uinidine
!istamine2 "!2# blockers
/imetidine
<anitidine !/l
Iodides
!erbal remedies
$onsteroidal anti%inflammatory drugs
-bu$rofen
7ulindac
&henothia'ines
(alicylates