Fever of Unknown Origin in Children

Organisms
Hx we dont want to miss
Workup approach
Empiric Abx
-Why we use cefataxin not ceftriaxone
Fever without a source vs Fever without an origin
Most are self limited viral infections. Symptomatic tx.
Sometimes due to common bacterial infections. Dx by hx and Phys exam and
require antibiotics without lab evaluation
Few situations, cause of fever is not easily identified. Categorized according
to duration of fever
-Fever without a source: <1 week of fever without known cause.
Further evaluation that includes lab tests or imaging.
-Fever of unknown origin:
>1week of fever without a clear source.
Infants and young children maintain higher temperatures than older children
and adults, primarily because of increased metabolic rate and body surface
to weight ratio
Fever: Core temperature of at least 38C (100.4F)
Fever is a natural defense mechanism against invading pathogens:
-Bacteria and viruses are heat sensitive
-Increasing metabolic rate accelerates immune system mobilization,
lymphocyte transformation, lysosome and neutrophil activity, and
phagocytosis.
-Increases lipolysis and proteolysis to reduce free glucose that can
used by invading organsims
-Body removes iron, zinc, and copper, which are critical cofactors in
viral and bacterial replication
FUO:
-Difficult to distinguish between benign and potentially life threatening
causes
-Causes include infectious, autoimmune, oncologic, neurologic, genetic,
factitious, and iatrogenic.
1990s
20-44% infectious
0-7% collagen-vascular

2-3% oncologic
67% undiagnosed.
Due to advent of PCR, improved culture techniques, better understanding of
atypical viral and bacterial pathogenesis and autoimmune processes: Earlier
diagnosis of FWS and few advancing to FUO category.

90% of cases had an identifiable cause:

50% infectious
10-20% collagen-vascular
10% oncologic
Most causes of undiagnosed FUO appear to be benign with spontaneous
resolution
Possibly due to prolonged viral syndromes or difficult to confirm atypical
bacterial infections.
EVALUATION:
I. Most important for evaluating FUO is a thorough, repeated history taking
and encouraging the patient and family to report any new, different, or
unusual signs or symptoms regardless of how trivial they may seem.
a. Most cases of FUO are diagnosed because important historical
information guides the direction of further evaluation.
1. Confirm and document fever
a. Parents typically report tactile or subjective fevers.
b. Ask if temperature was checked using a thermometer
2. Fever pattern:
a. Intermittent i.e. TB
b. recurrent i.e periodic fever disorders
c. relapsing i.e rat bite fever
d. remittent i.e. endocarditis, juvenile idiopathic arthritis
e. sustained i.e. pyogenic abscess
3. Frequency and timing
a. determine the fever curve and ability to document the fever in the
medical setting
4. History of:
a. repeated infections, diarrhea, or abnormal physical findings such as
a rash i.e. fever is the intital presentation of certain immunodeficiency
syndromes
b. atropy or autoimmune disease- fever is a result of autoimmune or
rhematologic cause
5. Ethnicity, race, family history, and genetic background

a. Periodic fever disorders run in the family and more common in

certain ethnicities
6. Geographic location and corresponding endemic pathogens known to
cause FUO should be taken into consideration. Including travel history.
a. Coccidioidomycosis in SW
b. Rocky Mountain Spotted fever- N. Carolina, Oklahoma, Arkansas,
Missouri, and Tennessee
7. Travel history
a. Animal exposure, unusual foods, insect bites, and sick contacts
8. Patients overall exposure to animals domestic or wild to evaluate for
zoonoses
9. Sick contacts or high risk exposures (i.e. recent travel to foreign countries,
prisons, the homeless)

Pseudo FUO:
-Successive episodes of benigh, self resolving infections with fever that is
perceived as one prolonger fever episode.
-Starts with an apparent infection (most often viral) which resolves by
proceeded by other febrile illness that is less well defined
Careful history, focused on afebrile periods between febrile episodes, and
keeping a fever diary if patient does not appear ill.
II Thorough physical exam should be performed that documents vital signs
and any reported weight loss

Management and Empiric treatment:

Pediatric FUO is often overtreated
Many FUO cases resolve without a diagnosis and empiric treatment may
mask the diagnosis of oncologic, infectious, and autoimmune diseases.
Steps:
1. Discontinue all nonessential pharmacologic agents including antipyretic
medications
a. Drug fever is a common source of FUO
b. Overall incidence of up to 5%
c. It can manifest itself at any time from start of medication
d. Inciting agents include antibiotics, ibuprofen, and acetaminophen
e. After discontinuation, fever is reduced in 24 hours or 2 half lives.
Resolves in 72-96 hours.
f. if drug fever is suspected and patient is taking multiple meds then
discontinue 1 drug at a time may identify the

Common causes of drug fever- TABLE

2. In an otherwise healthy, well-appearing child with FUO, empiric antibiotics
or anti-inflammatory agents are not recommended
a. Empiric antibiotics can delay the diagnosis of common infections of
FUO i.e. endocarditis, osteomyelitis, CNS infection, or abscesses.
b. Empiric anti-inflammatory agents i.e. Corticosteroids
1. It can be empriric treatment for autoimmune diseases
2. Also decreases the immune system, which increases
susceptibility to infection or worsen an underlying infection, and can impair
the diagnostic tests for oncologic testing and staging.
3. No contraindication in short term use. Immune suppression
manifests after 14-21 daily use.
4. Corticosteroid use if high suspicion for autoimmune and
inflammatory conditions, such as SLE or JIA, but not until oncologic causes
have been ruled out.
Prognosis and Outcome
-More favorable than adult population
-1970s, mortality rate of 6-9%
-Further study is needed to determine the mortality and overall
outcomes associated with pediatric FUO
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