Chapter 17 - Fever of Unknown Origin Flashcards
any febrile illness without an initially
obvious etiology
fever of unknown origin (FUO)
prolonged febrile illnesses without an established etiology
despite intensive evaluation and diagnostic testing
fever of unknown origin (FUO)
Definition of FUO
- Fever ≥38.3°C (≥101°F) on at least two occasions
- Illness duration of ≥3 weeks
- No known immunocompromised state
- Diagnosis that remains uncertain after a thorough history-taking,
physical examination, and the following obligatory investigations:
determination of erythrocyte sedimentation rate (ESR) and Creactive
protein (CRP) level; platelet count; leukocyte count and
differential; measurement of levels of hemoglobin, electrolytes, creatinine,
total protein, alkaline phosphatase, alanine aminotransferase,
aspartate aminotransferase, lactate dehydrogenase, creatine kinase,
ferritin, antinuclear antibodies, and rheumatoid factor; protein electrophoresis;
urinalysis; blood cultures (n = 3); urine culture; chest
x-ray; abdominal ultrasonography; and tuberculin skin test (TST) or
interferon γ release assay (IGRA).
accounts for about one-fifth of cases of FUO in Western countries
infection
common causes of FUO
infection
noninfectious inflammatory diseases (NIIDS)
neoplasms
diseases under NIIDS
collagen or rheumatic diseases, vasculitis
syndromes, granulomatous disorders, and autoinflammatory syndromes
50% of cases caused by infections in patients with FUO outside Western
nations are due what?
tuberculosis
repeated episodes
of fever interspersed with fever-free intervals of at least 2 weeks and
apparent remission of the underlying disease
recurrent fever
more common infectious
disease diagnoses that serves as differential diagnosis for FUO
Atypical
presentations of endocarditis, diverticulitis, vertebral osteomyelitis,
and extrapulmonary tuberculosis
quite rare but
should always be kept in mind as a cause of FUO since the presenting
symptoms can be nonspecific
Q fever and Whipple’s disease
results from exposure to animals or animal products, should be performed
when the patient lives in a rural area or has a history of heart
valve disease, an aortic aneurysm, or a vascular prosthesis.
Q fever
perform serologic testing
patients
with unexplained symptoms localized to the central nervous system,
gastrointestinal tract, or joints
Tropheryma whipplei (whipplei’s disease)
perform polymerase chain reaction test
diseases that could obtained when you travel to or (former) residence
in tropical countries or the American Southwest
infectious diseases such as malaria, leishmaniasis,
histoplasmosis, or coccidioidomycosis
disease that may be due to difficult-to-culture bacteria
such as nutritionally variant bacteria, HACEK organisms (including
Haemophilus parainfluenzae, H. paraphrophilus, Aggregatibacter actinomycetemcomitans,
A. aphrophilus, A. paraphrophilus, Cardiobacterium hominis,
C. valvarum, Eikenella corrodens, and Kingella kingae
Culture-negative endocarditis
sterile thrombotic disease that occurs as a paraneoplastic
phenomenon, especially with adenocarcinomas
Marantic endocarditis
seen in the context of systemic lupus erythematosus and antiphospholipid
syndrome
Sterile endocarditis
Of the NIIDs, these diseases are the common diagnoses in patients with FUO
large-vessel vasculitis, polymyalgia rheumatica, sarcoidosis,
familial Mediterranean fever, and adult-onset Still’s disease
of the NIIDs, this disease very is very rare and usually present in
young patients.
hereditary
autoinflammatory syndromes
HAS
can present at any age, is
uncommon but can often be diagnosed easily in a patient with FUO
who presents with urticaria, bone pain, and monoclonal gammopathy
Schnitzler syndrome
most common diagnosis of FUO among the neoplasms.
malignant lymphoma
miscellaneous causes of fever
drug-induced fever and exercise-induced hyperthermia
often accompanied by eosinophilia and also by lymphadenopathy,
which can be extensive
Drug-induced fever, including DRESS
(drug reaction with eosinophilia and systemic symptoms
More common causes of drug-induced fever
allopurinol, carbamazepine, lamotrigine, phenytoin, sulfasalazine,
furosemide, antimicrobial drugs (especially sulfonamides, minocycline,
vancomycin, β-lactam antibiotics, and isoniazid), some cardiovascular
drugs (e.g., quinidine), and some antiretroviral drugs (e.g., nevirapine)
characterized by an
elevated body temperature that is associated with moderate to strenuous
exercise lasting from half an hour up to several hours without an
increase in CRP level or ESR; typically these patients sweat during the
temperature elevation
Exercise-induced hyperthermia
fever artificially induced by the
patient—for example, by IV injection of contaminated water
more common among young women
in health care professions
Factitious fever
patient is normothermic
but manipulates the thermometer.
dissociation between
pulse rate and temperature.
fraudulent fever
FUO
in the elderly results from an atypical manifestation of a common disease, such as?
giant cell arteritis and polymyalgia rheumatica
most common infectious
disease associated with FUO in elderly patients, occurring much more
often than in younger patients.
Tuberculosis
most important step in the diagnostic workup in FUO
search for potentially diagnostic clues (PDCs)
through complete and
repeated history-taking and physical examination and the obligatory
investigations
blood and other cultures are not reliable
when samples are obtained during when
during antibiotic treatment
size
of enlarged lymph nodes usually decreases during when
glucocorticoid
treatment
low-cost
diagnostic tests remains obligatory in all patients with FUO in order
to separate cases that are caused by easily diagnosed diseases from
those that are not.
ultrasounds and chest xrays
preferred to abdominal
CT as an obligatory test because of relatively low cost, lack of radiation
burden, and absence of side effects.
Abdominal ultrasound
Given the absence of specific
symptoms in many patients and the relatively low cost of the test,
investigation of _________ appears to be a valuable screening
test in patients with FUO.
cryoglobulins
Specialized media should
be used when the history suggests uncommon microorganisms, such as _________
Histoplasma or Legionella
when is repeating blood or urine cultures useful?
previously cultured samples were collected during antibiotic treatment
or within 1 week after its discontinuation
FUO with headache
should prompt microbiologic examination of cerebrospinal fluid
(CSF) for organisms including ____________
herpes simplex virus (especially
type 2), Cryptococcus neoformans, and Mycobacterium tuberculosis
In
central nervous system tuberculosis, the CSF typically has _________
-elevated protein -lowered glucose concentrations -mononuclear pleocytosis
CSF protein level in CNS TB
100 to 500 mg/dL
CSF glucose concentration level in CNS TB
<45 mg/dL in 80% of
cases
usual CSF cell count
between 100 and 500 cells/μL.
should not be included in the diagnostic
workup of patients without PDCs for specific infections
Microbiologic serology
included in the obligatory investigations, but it may yield falsenegative
results in patients with miliary tuberculosis, malnutrition,
or immunosuppression.
TST
diseases that could yield false-negative result
miliary tuberculosis, malnutrition,
or immunosuppression
less influenced by
prior vaccination with bacille Calmette-Guérin or by infection with
nontuberculous mycobacteria, its sensitivity is similar to that of the
TST
IGRA
Granulomatous disease in liver or bone marrow biopsy
samples, for example, should always lead to a (re)consideration of
this diagnosis.
Miliary tuberculosis
diagnostics to be done to have highest diagnostic yield for miliary tuberculosis
liver biopsy for
acid-fast smear, culture, and polymerase chain
One of the first steps in diagnosing FUO, particularly in patients without signs of inflammation in
laboratory tests.
rule out factitious or fraudulent
fever
should be discontinued early in the
evaluation to exclude drug fever
medications, including nonprescription drugs
and nutritional supplements
If fever persists beyond _____ after
discontinuation of the suspected drug, it is unlikely that this drug is
the cause
72 hr
In patients without PDCs or with only misleading PDCs,
__________ may be useful in the early stage
of the diagnostic workup.
funduscopy
When the first-stage diagnostic tests do
not lead to a diagnosis, ________ should be performed, especially
when the ESR or the CRP level is elevated.
scintigraphy
In patients with recurrent fever lasting ______,
it is very unlikely that the fever is caused by infection or malignancy
> 2 years
noninvasive method
allowing delineation of foci in all parts of the body on the basis
of functional changes in tissues.
Scintigraphic imaging
Conventional scintigraphic methods used in clinical practice
67Ga-citrate scintigraphy and 111In- or 99mTc-labeled leukocyte scintigraphy.
diagnostic test that routinely
provide information on only part of the body
CT and MRI
diagnostic test that readily allows whole-body imaging
scintigraphy
established imaging procedure in FUO
18F-Fluorodeoxyglucose
(FDG) positron emission tomography (PET) combined
with CT
accumulates in tissues with a high rate of glycolysis, which
occurs not only in malignant cells but also in activated leukocytes
and thus permits the imaging of acute and chronic inflammatory
processes
FDG
Normal uptake may obscure pathologic foci in the ________________
brain,
heart, bowel, kidneys, and bladder
FDG uptake in the heart, which
obscures endocarditis, may be prevented by consumption of a
___________ before the PET investigation
low-carbohydrate diet
offers the advantages of higher resolution,
greater sensitivity in chronic low-grade infections, and
a high degree of accuracy in the central skeleton.
FDG-PET/CT
they often identify the anatomic location of a particular
ongoing metabolic process and, with the help of other techniques
such as biopsy and culture, facilitate timely diagnosis and treatment
scintigraphic techniques
Abnormalities
found with scintigraphic techniques often need to be confirmed
by ____________
pathology and/or culture of biopsy specimens
If no diagnosis is reached despite scintigraphic and PDC-driven
histologic investigations or culture, ____________________ should be considered
second-stage screening diagnostic
tests
may be used as screening procedures at a later
stage of the diagnostic protocol because of their noninvasive nature
and high sensitivity.
chest
and abdominal CT
Several studies
have shown a high prevalence of _________ among patients
with FUO, with rates up to 17% among elderly patients
giant cell arteritis
recommended for patients ≥55 years of age in a later stage of the
diagnostic protocol
temporal artery biopsy
will not be useful in vasculitis
limited to the temporal arteries because of the small diameter of
these vessels and the high levels of FDG uptake in the brain
FDG-PET/CT
good indication
for empirical antibiotic therapy
hemodynamic instability or neutropenia
when does trial of therapy for TB should be started?
TST or IGRA is positive
granulomatous disease is present with anergy and sarcoidosis
seems unlikely
If the fever does not respond after ______ of
empirical antituberculous treatment, another diagnosis should be
considered.
6 weeks
highly effective in preventing attacks of familial Mediterranean
fever but is not always effective once an attack is well
under way.
Colchicine
If the fever persists and the source remains
elusive after completion of the later-stage investigations, supportive
treatment with _______ can
be helpful
NSAIDS
their use should be avoided unless infectious diseases and malignant
lymphoma have been largely ruled out and inflammatory
disease is probable and is likely to be debilitating or threatening
NSAIDs and glucocorticoids
a recombinant
form of the naturally occurring IL-1 receptor antagonist (IL-1Ra),
blocks the activity of both IL-1α and IL-1β
Anakinra
extremely
effective in the treatment of many autoinflammatory syndromes,
such as familial Mediterranean fever, cryopyrin-associated periodic
syndrome, tumor necrosis factor receptor–associated periodic syndrome,
mevalonate kinase deficiency (hyper IgD syndrome), and
Schnitzler syndrome
Anakinra
A therapeutic
trial with _____ can be considered in patients whose FUO has
not been diagnosed after later-stage diagnostic tests.
Anakinra
can
provide improved control without the metabolic, immunologic, and
gastrointestinal side effects of glucocorticoid administration.
monotherapy with IL-1 blockade
