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Fever
Assit. Prof. Dr. Suat Biçer
Yeditepe University, Faculty of Medicine
Child Health and Pediatrics Department
AMAÇLAR
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Çocukluk çağında ateş nedenleri konusunda bilgi
sahibi olabilmek,
Ne zaman ateş ciddi hastalık belirtisidir sorusunu
yanıtlayabilmek,
Ateşli çocuğa yaklaşım konusunda bilgi sahibi
olmak,
Yineleyen ateşte etiyolojik faktörler ve tedavi
yöntemleri konusunda bilgi sahibi olmak,
Ateşli çocuğa müdahale yöntemleri ve
antipiretikler konusunda bilgi sahibi olmak.
What is the definition of fever in
children?
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≥ 39°C
> 39°C
≥ 40°C
≥ 38°C
> 38°C
> 37.9°C
> 37°C
≥ 36.5°C
> 36.5°C
What is the definition of
hyperpyrexia in children?
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The same definition for
fever,
≥ 38°C
> 39°C
> 37.9°C
> 37°C
≥ 36.5°C
> 36.5°C
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≥ 39°C
> 38°C
> 37.9°C
> 37°C
≥ 36.5°C
> 36.5°C
> 40°C
> 41°C
Definition
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Fever is defined as a rectal temperature
≥38°C, and a value >40°C is called
hyperpyrexia.
Body temperature fluctuates in a defined
normal range (36.6°C-37.9°C rectally), so
that the highest point is reached in early
evening and the lowest point is reached in
the morning.
Any abnormal rise in body temperature
should be considered a symptom of an
underlying condition.
Where is regulated the body
temperature?
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Body temperature is regulated by thermosensitive
neurons located in the supraoptic and posterior
hypothalamus that respond to changes in blood
temperature as well as cold and warm receptors
located in capillary and venous vessels.
Body temperature is regulated by thermosensitive
neurons located in the preoptic or anterior
hypothalamus that respond to changes in blood
temperature as well as cold and warm receptors
located in skin and muscles.
Pathogenesis
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Thermoregulatory responses include redirecting blood
to or from cutaneous vascular beds, increased or
decreased sweating, regulation of extracellular fluid
volume via arginine vasopressin, and behavioral
responses, such as seeking a warmer or cooler
environmental temperature.
FEVER RESPONSE
Infection, toksins,
injury,
inflamation,
immunolojic reactions,
Vasomotor area
Monocyt, neutrophil,
lymphocyt,
endotel, glial,
mesenchimal cells
Increased set point
Monoamins and
Calcium
cAMP
Prostoglandin E2
Pyrojenic cytokins,
IL-1, TNF, IFN,
IL-6
Endotel
Circulation
Circumventricular area
Which mechanisms can produce
fever?
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Pyrogens,
Heat production exceeding loss,
Defective heat loss
The first mechanism involves endogeneous and
exogenous pyrogens that raise the
hypothalamic temperature set point.
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Endogenous pyrogens include the cytokines
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interleukin 1 (IL)-1 and IL-6,
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tumor necrosis factor-α (TNF-α), and
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interferon (IFN)-β and IFN-γ.
Stimulated leukocytes and other cells produce lipids that
also serve as endogenous pyrogens.
The best-studied lipid mediator is ................., which attaches to the
................. receptors in the ................. to produce the new
temperature set point.
The best-studied lipid mediator is prostaglandin (PG)E2, which attaches to
the prostaglandin receptors in the hypothalamus to produce the new
temperature set point.
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Exogenous pyrogens or substances that come
from outside the body include mainly infectious
pathogens and drugs.
Microbes, microbial toxins, or other products of
microbes are the most common exogenous
pyrogens and stimulate macrophages and other
cells to produce endogenous pyrogens.
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Some substances produced within the body are
not pyrogens but are capable of stimulating
endogenous pyrogens.
Such substances include antigen-antibody
complexes in the presence of complement,
complement components, lymphocyte products,
bile acids, and androgenic steroid metabolites.
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Endotoxin is one of the few substances that can
directly affect thermoregulation in the
hypothalamus as well as stimulate endogenous
pyrogen release.
Many drugs cause fever, and the mechanism for
increasing body temperature varies with the class
of drugs.
Drugs that are known to cause fever include
vancomycin, amphotericin B, and allopurinol.
Along with infectious diseases and drugs,
malignancy and inflammatory diseases can cause
fever through the production of endogenous
pyrogens.
Second and third mechanisms
that leads to fever:
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Heat production exceeding heat loss is the
second mechanism that leads to fever, with
examples including salicylate poisoning and
malignant hyperthermia.
Defective heat loss is the third mechanism of
fever genesis, for example, in children with
ectodermal dysplasia or victims of severe heat
exposure.
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What are the causes of fever? (organized into 4
main categories)
1- Infections
Etiology
2- Inflammatory diseases
3- Neoplastic diseaes
4- Miscellaneous
What are the most common causes of acute
fever and hyperpyrexia?
1- Self-limited viral infections (common cold,
gastroenteritis)
2- Uncomplicated bacterial infections (otitis
media, pharyngitis, sinusitis)
What is the limit of fever?
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40°C
41°C
42°C
43°C
45°C
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The body temperature should not rise above
potentially lethal levels (41.7°C) in the
neurologically intact child unless extreme
hyperthermic environmental conditions are
present or other extenuating circumstances exist,
such as underlying malignant hyperthermia or
thyrotoxicosis.
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The pattern of the fever can provide clues to the
underlying etiology.
Viral infections typically are associated with a
slow decline of fever over a week, whereas
bacterial infections are associated with a prompt
resolution of fever after effective antimicrobial
treatment is employed.
Although administration of antimicrobial agents
can result in a very rapid elimination of bacteria,
if tissue injury has been extensive, the
inflammatory response and fever can continue
for days after all microbes have been eradicated.
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Intermittent fever is an exaggerated circadian
rhythm that includes a period of normal
temperatures on most days; extremely wide
fluctuations may be termed septic or hectic
fever.
Sustained fever is persistent and does not vary
by more than 0.5°C/day.
Remittent fever is persistent and varies by more
than 0.5°C/day.
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Relapsing fever is characterized by febrile
periods that are separated by intervals of normal
temperature; tertian fever occurs on the first and
third days (malaria caused by Plasmodium vivax),
and quartan fever occurs on the first and fourth
days (malaria caused by Plasmodium malariae).
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Diseases characterized by relapsing fevers
should be distinguished from infectious diseases
that have a tendency to relapse.
Biphasic fever indicates a single illness with 2
distinct periods (camelback fever pattern);
poliomyelitis is the classic example. A biphasic
course is also characteristic of other enteroviral
infections, leptospirosis, dengue fever, yellow
fever, Colorado tick fever, spirillary rat-bite fever
(Spirillum minus), and the African hemorrhagic
fevers (Marburg, Ebola, and Lassa fevers).
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The term periodic fever is used narrowly to describe
fever syndromes with a regular periodicity (cyclic
neutropenia and PFAPA [periodic fever, aphthous
stomatitis, pharyngitis, and adenopathy]) or more
broadly to include disorders characterized by recurrent
episodes of fever that do not follow a strictly periodic
pattern (familial Mediterranean fever, Hibernian fever,
TNF-receptor–associated periodic syndrome
[TRAPS], hyper-IgD syndrome, the Muckle-Wells
syndrome).
Factitious fever, or self-induced fever, may be caused
by intentional manipulation of the thermometer or
injection of pyrogenic material.
INFECTIOUS CAUSES
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Relapsing fever (Borrelia recurrentis)
Acute rheumatic fever
Q fever (Coxiella burnetii)
Visceral leishmaniasis
Typhoid fever (Salmonella typhi)
Lyme disease (Borrelia burgdorferi)
Syphilis (Treponema pallidum)
Malaria
Tuberculosis
Babesiosis
Histoplasmosis
Respiratory viral infections
Coccidioidomycosis
Blastomycosis
Melioidosis (Pseudomonas pseudomallei)
Lymphocytic choriomeningitis (LCM) infection
Dengue fever
Yellow fever
Leptospirosis
Brucellosis
NONINFECTIOUS CAUSES
Behçet disease
Crohn disease
Weber-Christian disease (panniculitis)
Leukoclastic angiitis
Sweet syndrome
Systemic lupus erythematosus
PERIODIC FEVER SYNDROMES
Familial Mediterranean fever
Cyclic neutropenia
Periodic fever, aphthous stomatitis, pharyngitis,
adenopathy (PFAPA)
Hyper IgD syndrome
Hibernian fever (tumor necrosis factor super-family IgAassociated syndrome [TRAPS])
Muckle-Wells syndrome
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The double quotidian fever (or fever that peaks
twice in 24 hours) is classically associated with
inflammatory arthritis. In general, a single isolated
fever spike is not associated with an infectious
disease. Such a spike can be attributed to the
infusion of blood products and some drugs, as
well as to some procedures, or to manipulation of
a catheter on a colonized or infected body surface.
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Temperatures in excess of 41°C are most often
associated with a noninfectious cause.
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Causes for very high temperatures (>41°C)
include central fever (resulting from central
nervous system (CNS) dysfunction involving the
hypothalamus), malignant hyperthermia,
malignant neuroleptic syndrome, drug fever, or
heatstroke.
Hypothermia
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Temperatures that are lower than normal
(<36°C) can be associated with sepsis but
are more commonly related to cold
exposure, hypothyroidism, or overuse of
antipyretics.
Clinical Features
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The clinical features of fever can range from no
symptoms at all to extreme malaise.
Children might complain of feeling hot or cold,
display facial flushing, and experience shivering.
Fatigue and irritability may be evident.
Parents often report that the child looks ill or
pale and has a decreased appetite.
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The underlying etiology also produces
accompanying symptoms.
Although the underlying etiologies can manifest
in varied ways clinically, there are some
predictable features.
For instance, fever with petechiae in an illappearing patient indicates the high possibility
of life-threatening conditions such as
meningococcemia, Rocky Mountain spotted
fever, or acute bacterial endocarditis.
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Changes in heart rate, most commonly
tachycardia, accompany fever. Relative
tachycardia, when the pulse rate is elevated out
of proportion to the temperature, is usually due
to noninfectious diseases or infectious diseases
in which a toxin is responsible for the clinical
manifestations.
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Relative bradycardia (temperature-pulse
dissociation), when the pulse rate remains low in the
presence of fever, can accompany typhoid fever,
brucellosis, leptospirosis, or drug fever.
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Bradycardia in the presence of fever also may be a
result of a conduction defect resulting from cardiac
involvement with acute rheumatic fever, Lyme
disease, viral myocarditis, or infective endocarditis.
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Evaluation
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Most acute febrile episodes in a normal host can be
diagnosed by a careful history and physical
examination and require few, if any, laboratory tests.
Because infection is the most likely etiology of the
acute fever, the evaluation should initially be geared
to discovering an underlying infectious cause.
The details of the history should include the
onset and pattern of fever and any
accompanying signs and symptoms.
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The patient often displays signs or symptoms that
provide clues to the cause of the fever. Exposures to
other ill persons at home, daycare, and school should
be noted, along with any recent travel or medications.
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The past medical history should include information
about underlying immune deficiencies or other major
illnesses and receipt of childhood vaccines.
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In the acutely febrile child, the physical examination
should focus on any localized complaints, but a
complete head-to-toe screen is recommended, because
clues to the underlying diagnosis may be found.
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For example, palm and sole lesions may be discovered
during a thorough skin examination and provide a clue
for infection with coxsackievirus.
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Vital signs should include pulse oximetry, because
hypoxia indicates lower respiratory tract disease.
EVALUATION OF ACUTE
FEVER
Thorough history: onset, other symptoms, exposures (daycare,
school, family, pets, playmates), travel, medications, other
EVALUATION
OF ACUTE FEVER
underlying
disorders, immunizations
Physical examination: complete, with focus on localizing symptoms
Laboratory studies on a case-by-case basis:
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Rapid antigen testing
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Nasopharyngeal: respiratory viruses
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Throat: group A streptococcus
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Stool: rotavirus
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Throat culture
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Blood: complete blood count, blood culture, C-reactive protein,
sedimentation rate
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Urine: urinalysis, culture
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Stool: hemocult, culture
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Cerebrospinal fluid: cell count, glucose, protein, Gram stain, culture
Chest radiograph or other imaging studies on a case-by-case basis
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If a fever has an obvious cause, then the evaluation is
complete, no further testing is advised, and care is
tailored to the underlying diagnosis with as-needed
re-evaluation.
If the cause of the fever is not apparent, then further
diagnostic testing should be considered on a caseby-case basis.
The history of presentation and abnormal physical
examination findings guide the evaluation. The child
with respiratory symptoms and hypoxia can require a
chest radiograph or rapid antigen testing for RSV or
influenza.
The child with pharyngitis can benefit from rapid
antigen detection testing for group A Streptococcus and
a throat culture.
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Dysuria, back pain, or history of vesicoureteral
reflux should prompt a urinalysis and urine
culture, and bloody diarrhea should prompt a
stool culture.
A complete blood count and blood culture should
be considered in the ill-appearing child, along
with cerebrospinal fluid studies if the child has
neck stiffness.
Well-defined high-risk groups require a moreextensive evaluation on the basis of age,
associated disease, or immunodeficiency status
and might warrant prompt antimicrobial therapy
before a pathogen is identified.
Treatment
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Although fear of fever is a common parental worry,
evidence is lacking to support the belief that high fever
can result in brain damage or other bodily harm, except
in rare instances of febrile status epilepticus and heat
stroke.
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Treating fever in self-limiting illnesses for the sole reason
of bringing the body temperature back to normal is not
necessary in the otherwise healthy child.
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Most evidence suggests that fever is an adaptive response
and should be treated only in selected circumstances.
In humans, increased temperatures are associated with
decreased microbial replication and an increased
inflammatory response.
• Increases neutrophil migration,
• Antibacterial agents such as released from neutrophils superoxide anion
production increases.
• Increases the production of interferon
• Enhances the antiviral and antitumor activity of interferon.
• Activation of T-helper cells, and cytotoxic activity of expression increases.
• Promotes the release of lactoferrin.
Accelerate the killing of intracellular bacteria.
Increases the bactericidal activity of antimicrobial agents.
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Although fever can have beneficial effects, it also
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- increases
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Fever can exacerbate;
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- cardiac insufficiency in patients with heart disease or
- oxygen consumption,
- carbon dioxide production,
- cardiac output
chronic anemia (e.g., sickle cell disease),
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- pulmonary insufficiency in patients with chronic lung
disease,
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- metabolic instability in patients with diabetes mellitus
or inborn errors of metabolism.
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Basal metabolic rate leads to a six-fold increase,
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Body temperature increase from 38 to 41 ⁰ C with
increasing oxygen consumption by 20%,
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The oxygen affinity of hemoglobin is reduced,
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Degrees above the normal body temperature of a need to
keep the increase in the basal metabolic rate of 10-12.5%.
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Children between the ages of 6 mo and 6 yr are
at increased risk for simple febrile seizures.
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Children with idiopathic epilepsy also often have
an increased frequency of seizures associated
with a fever.
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Fever with temperatures <39°C in healthy children
generally does not require treatment.
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However, as temperatures become higher, patients tend to
become more uncomfortable, and treatment of fever is
then reasonable.
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If a child is included in one of the high-risk groups or if
the child's caregiver is concerned that the fever is
adversely affecting the child's behavior and causing
discomfort, treatment may be given to hasten the
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Other than providing symptomatic relief,
antipyretic therapy does not change the course of
infectious diseases.
Encouraging good hydration is the first step to
replace fluids that are lost related to the increased
metabolic demands of fever.
Antipyretic therapy is beneficial in high-risk
patients who have chronic cardiopulmonary
diseases, metabolic disorders, or neurologic
diseases and in those who are at risk for febrile
seizures.
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Hyperpyrexia (>40°C) indicates greater risk of
hypothalamic disorders or CNS hemorrhage and
should be treated with antipyretics.
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Some studies have shown that hyperpyrexia may be
associated with a significantly increased risk of
serious bacterial infection, but other studies have
not substantiated this relationship.
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High fever during pregnancy may be teratogenic.
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Acetaminophen at a dose of 10-15 mg/kg/dose every
4 hr and ibuprofen in children older than 6 months at
a dose of 5-10 mg/kg/dose every 8 hours are the
most commonly employed antipyretics.
Antipyretics reduce fever by reducing production of
prostaglandins. If used appropriately, antipyretics are
safe; potential adverse effects include liver damage
(acetaminophen) and gastrointestinal or kidney
disturbances (ibuprofen).
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To reduce fever most safely, the caregiver
should choose one type of medication and
clearly record the dose and time of
administration, so overdosage does not occur,
especially if multiple caregivers are involved in
the management.
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Physical measures such as tepid baths and cooling
blankets are not considered effective to reduce fever.
Evidence is also scarce for the use of complementary
and alternative medicine interventions.
Fever due to specific underlying etiologies resolves
when the condition is properly treated.
Examples include administration of intravenous
immunoglobulin to treat Kawasaki disease or the
administration of antibiotics to treat bacterial
infections.
Fever without a Focus
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Fever without a focus refers to a rectal
temperature of 38°C or higher as the sole
presenting feature.
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The terms “fever without localizing signs”
and “fever of unknown origin” (FUO) are
subcategories of fever without a focus.
Fever without Localizing Signs
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Fever of acute onset, with duration of <1 wk
and without localizing signs, is a common
diagnostic dilemma in children <36 mo of age.
The etiology and evaluation of fever without
localizing signs depends on the age of the child.
Traditionally, 3 age groups are considered:
neonates or infants to 1 mo of age, infants >1
mo to 3 mo of age, and children >3 mo to 3 yr
of age.
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In 1993, practice guidelines were published to aid the
clinician in evaluating the otherwise healthy 0 to 36
mo old with fever without a source.
However, with the advent and extensive use of the
conjugate Haemophilus influenzae type b (Hib) and
Streptococcus pneumoniae vaccines, the rates of infections
with these 2 pathogens have decreased substantially.
As a consequence, modifications to the 1993
guidelines have been advocated as described later.
Children in high-risk groups require a moreaggressive approach and consideration of a broader
differential diagnosis.
FEBRILE PATIENTS AT INCREASED RISK FOR SERIOUS
BACTERIAL INFECTIONS
RISK GROUP
DIAGNOSTIC CONSIDERATIONS
IMMUNOCOMPETENT PATIENTS
Neonates (<28 days)
Sepsis and meningitis caused by group B streptococcus,
Escherichia coli, Listeria monocytogenes; neonatal herpes simplex
virus infection, enteroviruses
Infants 1-3 mo
Serious bacterial disease in 10-15%, including bacteremia in 5%;
urinary tract infection
Occult bacteremia in <0.5% of children immunized with both
Infants and children 3-36
Haemophilus influenzae type b and pneumococcal conjugate
mo
vaccines; urinary tract infections
Hyperpyrexia (>40°C)
Meningitis, bacteremia, pneumonia, heatstroke, hemorrhagic
shock-encephalopathy syndrome
Fever with petechiae
Bacteremia and meningitis caused by Neisseria meningitidis, H.
influenzae type b, and Streptococcus pneumoniae
IMMUNOCOMPROMISED PATIENTS
Sickle cell disease
Sepsis, pneumonia, and meningitis caused by S.
pneumoniae, osteomyelitis caused by Salmonella and
Staphylococcus aureus
Asplenia
Bacteremia and meningitis caused by N. meningitidis, H.
influenzae type b, and S. pneumoniae
Complement or
properdin deficiency
Sepsis caused by N. meningitidis
Agammaglobulinemia Bacteremia, sinopulmonary infections
AIDS
S. pneumoniae, H. influenzae type b, and Salmonella
infections
Congenital heart
disease
Infective endocarditis; brain abscess with right-to-left
shunting
Central venous line
Staphylococcus aureus, coagulase-negative staphylococci,
Candida
Malignancy
Bacteremia with gram-negative enteric bacteria, S. aureus,
and coagulase-negative staphylococci; fungemia with
Candida and Aspergillus
Neonates
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Neonates who experience fever without focus are a
challenge to evaluate because they display limited
signs of infection, making it difficult to clinically
distinguish between a serious bacterial infection and
self-limited viral illness.
Immature immune responses in the first few
months of life also increase the significance of fever
in the young infant.
In general, neonates who have a fever and do not
appear ill have a 7% risk of having a serious
bacterial infection.
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Serious bacterial infections include occult
bacteremia, meningitis, pneumonia, osteomyelitis,
septic arthritis, enteritis, and urinary tract
infections.
Although neonates with serious infection can
acquire community pathogens, they are mainly at
risk for late-onset neonatal bacterial diseases
(group B streptococci, Escherichia coli, and Listeria
monocytogenes) and perinatally acquired herpes
simplex virus (HSV) infection.
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Practice guidelines recommend that if a neonate
has had a fever recorded at home by a reliable
parent, the patient should be treated as a febrile
neonate.
If excessive clothing and blankets encasing the
infant are suspected of falsely elevating the body
temperature, then the excessive coverings should
be removed and the temperature retaken in 15 to
30 minutes.
If body temperature is normal after the covers are
removed, then the infant is considered afebrile.
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Owing to the unreliability of physical findings and
the presence of an immature immune system, all
febrile neonates should be hospitalized; blood,
urine, and cerebrospinal fluid (CSF) should be
cultured, and the child should receive empirical
intravenous antibiotics.
CSF studies should include cell counts, glucose and
protein levels, Gram stain, and culture; HSV and
enterovirus polymerase chain reaction should be
considered.
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Stool culture and chest radiograph may also be
part of the evaluation.
Combination antibiotics such as ampicillin and
cefotaxime are recommended.
Acyclovir should be included if HSV infection is
suspected owing to the presence of CSF
pleocytosis or known maternal history of genital
HSV, especially at the time of delivery.
1 Month to 3 Months
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The large majority of children with fever without
localizing signs in the 1-3 mo age group likely have a
viral syndrome.
In contrast to bacterial infections, most viral diseases
have a distinct seasonal pattern: respiratory syncytial
virus and influenza A virus infections are more
common during the winter, whereas enterovirus
infections usually occur in the summer and fall.
Although a viral infection is the most likely etiology,
fever in this age group should always suggest the
possibility of serious bacterial disease.
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Organisms to consider include group B
streptococcus, L. monocytogenes, Salmonella enteritis,
E. coli, Neisseria meningitidis, S. pneumoniae, Hib, and
Staphylococcus aureus.
Pyelonephritis is more common in uncircumcised
infant boys and infants with urinary tract
anomalies.
Other potential bacterial diseases in this age group
include otitis media, pneumonia, omphalitis,
mastitis, and other skin and soft tissue infections.
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Ill-appearing (toxic) febrile infants ≤3 mo of age require
prompt hospitalization and immediate parenteral
antimicrobial therapy after cultures of blood, urine, and
CSF are obtained.
Ampicillin (to cover L. monocytogenes and
enterococcus) plus either ceftriaxone or cefotaxime is an
effective initial antimicrobial regimen for ill-appearing
infants without focal findings.
This regimen is effective against the usual bacterial
pathogens causing sepsis, urinary tract infection, and
enteritis in young infants.
However, if meningitis is suspected because of CSF
abnormalities, vancomycin should be included to treat
possible penicillin-resistant S. pneumoniae until the
results of culture and susceptibility tests are known.
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Many academic institutions have investigated the
optimal management of low-risk patients in this age
group with fever without a focus.
The use of viral diagnostic studies (enteroviruses,
respiratory viruses, rotavirus, and herpesvirus) in
combination with the Rochester Criteria or similar
criteria can enhance the ability to determine which
infants are at high risk for serious bacterial infections.
Febrile infants in whom a virus has been detected are at
low or no risk of a serious bacterial infection.
Well-appearing infants 1-3 mo of age can be managed
safely using low-risk laboratory and clinical criteria as
indicated in Table, if reliable parents are involved and
close follow-up is assured.
LOW RISK CRITERIA IN 1-3 MONTHS OLD WITH
FEVER
BOSTON CRITERIA
nfants are at low risk if they appear well, have normal
physical examination, have a caretaker reachable by
elephone, and laboratory tests are as follows:
•
•
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CBC: <20,000 WBC/mm3
Urine: negative leukocyte esterase
CSF: leukocyte count less than 10 × 106/L,
•
CBC: <15,000 WBC/mm3; band: total neutrophil
ratio <0.2
Urine: <10 WBC/HPF; no bacteria on Gram stain
CSF: <8 WBC/mm3; no bacteria on Gram stain
Chest radiograph: no infiltrate
Stool: no RBC; few to no WBC
PHILADELPHIA PROTOCOL
nfants are at low risk if they appear well, have a normal
physical examination, and laboratory tests are as follows:
•
•
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PITTSBURGH GUIDELINES
Infants are at low risk if they appear well, have a
normal physical examination, and laboratory tests are
as follows:
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CBC: 5,000-15,000 WBC; peripheral absolute
band count <1500/mm3
Urine (enhanced urinalysis): 9 WBC/mm3
and no bacteria on Gram stain
CSF: 5 WBC/mm3 and negative Gram stain;
if bloody tap, then WBC : RBC ≤ 1 : 500
Chest
radiograph: no infiltrate
Stool: 5 WBC/HPF with diarrhea
ROCHESTER CRITERIA
Infants are at low risk if they appear well, have a
normal physical examination, and laboratory findings
are as follows:
•
•
•
CBC: 5,000-15,000 WBC/mm3; absolute
band count ≤1500/mm3
Urine: <10 WBC/HPF at 40×
Stool: <5 WBC/HPF if diarrhea


Infants 1-3 mo of age with fever who appear
generally well; who have been previously healthy;
who have no evidence of skin, soft tissue, bone,
joint, or ear infection; and who have a peripheral
white blood cell (WBC) count of 5,000-15,000
cells/µL, an absolute band count of <1,500
cells/µL, and normal urinalysis and negative culture
(blood and urine) results are unlikely to have a
serious bacterial infection.
The negative predictive value with 95% confidence
of these criteria for any serious bacterial infection is
>98% and for bacteremia is >99%.


Among serious bacterial infections,
pyelonephritis is the most common and may be
seen in well-appearing infants who have fever
without a focus or in those who appear ill.
Urinalysis may be negative in infants <2 mo of
age with pyelonephritis.
Bacteremia is present in <30% of infants with
pyelonephritis.




The decision to obtain CSF studies in the wellappearing 1-3 mo old infant depends on the
decision to administer empirical antibiotics.
If close observation without antibiotics is planned,
a lumbar puncture may be deferred.
If the child deteriorates clinically, a full sepsis
evaluation should be performed, and intravenous
antibiotics should be administered.
If empirical antibiotics are initiated, CSF studies
should be obtained, preferably before administering
antibiotics.
3 Months to 36 Months of Age




Approximately 30% of febrile children in the 3-36 mo age
group have no localizing signs of infection.
Viral infections are the cause of the vast majority of fevers in
this population, but serious bacterial infections do occur and
are caused by the same pathogens listed for patients 1-3 mo of
age, except for the perinatally acquired infections.
S. pneumoniae, N. meningitidis, and Salmonella account for most
cases of occult bacteremia.
Hib was an important cause of occult bacteremia in young
children before universal immunization with conjugate Hib
vaccines and remains common in underdeveloped countries
that have not implemented these vaccines.


Risk factors indicating increased probability of occult
bacteremia include temperature ≥39°C, WBC count
≥15,000/µL, and elevated absolute neutrophil count,
band count, erythrocyte sedimentation rate, or Creactive protein.
The incidence of bacteremia and/or pneumonia or
pyelonephritis, among infants 3-36 mo of age
increases as the temperature (especially >40°C) and
WBC count (especially >25,000) increase.




However, no combination of laboratory tests or
clinical assessment is completely accurate in predicting
the presence of occult bacteremia.
Socioeconomic status, race, sex, and age (within the
range of 3-36 mo) do not appear to affect the risk for
occult bacteremia.
Without therapy, occult bacteremia due to
pneumococcus can resolve spontaneously without
sequelae, can persist, or can lead to localized
infections such as meningitis, pneumonia, cellulitis,
pericarditis, osteomyelitis, or suppurative arthritis.
The pattern of sequelae may be related to host factors
and the offending organism.




In some children, the occult bacteremic illness can
represent the early signs of serious localized infection
rather than a transient disease state.
Hib bacteremia is characteristically associated with a
higher risk for localized serious infection than is
bacteremia due to S. pneumoniae.
Hospitalized children with Hib bacteremia often develop
focal infections, such as meningitis, epiglottitis,
cellulitis, pericarditis, or osteoarticular infection, and
spontaneous resolution of bacteremia is rare.
Among patients with pneumococcal bacteremia (occult
or focal), spontaneous resolution occurs in 30-40%, with
a higher rate of spontaneous resolution among wellappearing children.

Important bacterial infections among children 336 mo of age with localizing signs include otitis
media, sinusitis, pneumonia (not always evident
without a chest x-ray), enteritis, urinary tract
infection, osteomyelitis, and meningitis.


Treatment of toxic-appearing febrile children 3-36
mo of age who do not have focal signs of infection
includes hospitalization and prompt institution of
antimicrobial therapy after specimens of blood,
urine, and CSF are obtained for culture.
Consensus practice guidelines published in 1993
recommended that children 3-36 mo of age who
have a temperature of <39°C and do not appear
toxic be observed as outpatients without performing
diagnostic tests or administering antimicrobial agents.

For nontoxic-appearing infants with a rectal
temperature of ≥39°C, options include obtaining a
blood culture and administering empirical antibiotic
therapy (ceftriaxone, a single dose of 50 mg/kg, not to
exceed 1 g); if the WBC count is >15,000/µL,
obtaining a blood culture and beginning empirical
antibiotic therapy; or obtaining a blood culture and
observing as outpatients without empirical antibiotic
therapy, with return for re-evaluation within 24 hr.



Guidelines for managing febrile children 3-36 mo of age who
have received both Hib and S. pneumoniae conjugate vaccines
have not been established, but careful observation without
empirical administration of antibiotic therapy is generally
prudent.
Because fully vaccinated young children are at a much lower
risk of occult bacteremia and meningitis as the cause of acute
fever without localizing signs, some advocate that the only
laboratory tests needed in this age group when temperature is
>39°C are a urinalysis and urine culture for circumcised boys
<6 mo of age and uncircumcised boys and all girls <24 mo of
age.
Regardless of the management option , the family should be
instructed to return immediately if the child's condition
deteriorates or new symptoms develop.
GROUP
MANAGEMENT
MANAGEMENT
OF FEVER WITHOUT
LOCALIZING SIGNS
Any toxic-appearing child 0-36 mo
and temperature ≥38°C
Hospitalize, broad cultures plus other tests,*
parenteral antibiotics
Child <1 mo and temperature ≥38°C
Hospitalize, broad cultures plus other tests,*
parenteral antibiotics
Child 1-3 mo and temperature ≥38°C
Two-step process







1) Determine risk based on history, physical
examination, and laboratory studies.
Low risk:
Uncomplicated medical history, Normal physical
examination, Normal laboratory studies
Urine: negative leukocyte esterase, nitrite and <10
WBC/HPF
Peripheral blood: 5,000-15,000 WBC/mm3; <1,500 bands
or band : total neutrophil ratio <0.2
Stool studies if diarrhea (no RBC and <5 WBC/HPF)
CSF cell count (<8 WBC/mm3) and negative Gram stain
Chest radiograph without infiltrate
2) If child fulfills all low-risk criteria, administer no
antibiotics, ensure follow-up in 24 hr and access to
emergency care if child deteriorates.
Daily follow-up should occur until blood, urine, and CSF
cultures are final. If any cultures are positive, child returns
for further evaluation and treatment.
If child does not fulfill all low-risk criteria, hospitalize and
administer parenteral antibiotics until all cultures are final
and definitive diagnosis determined and treated.
GROUP
Child 3-36 mo
Reassurance that diagnosis is likely self-limiting viral infection, but
and temperature advise return with persistence of fever, temperatures >39°C, and
38-39°C
new signs and symptoms
Child 3-36 mo
and temperature
>39°C
Two-step process:
1) Determine immunization status
2) If received conjugate pneumococcal and H. influenzae type b
vaccines, obtain urine studies (urine WBC, leukocyte esterase,
nitrite, and culture) for all girls, all boys <6 mo old, all
uncircumcised boys <2 yr, all children with recurrent urinary tract
infections
If did not receive conjugate pneumococcal and H. influenzae type
b vaccines, manage according to the 1993 Guidelines (see Baraff et
al. Pediatrics 1993;92:1-12)



Empirical antibiotic therapy for well-appearing
children <36 mo of age who have not received Hib
and S. pneumoniae conjugate vaccines and who have a
rectal temperature of >39°C and a WBC count of
>15,000/µL is strongly recommended.
If blood cultures are obtained and S. pneumoniae is
isolated from the blood, the child should return to the
physician as soon as possible after the culture results
are known.
If the child appears well, is afebrile, and has a normal
physical exam, a second blood culture should be
obtained and the child should be treated with 7-10
days of oral antimicrobial therapy.


If the child appears ill and continues to have
fever with no identifiable focus of infection at
the time of follow-up, or if H. influenzae, or N.
meningitidis is present in the initial blood culture,
the child should have a repeat blood culture, be
evaluated for meningitis (including lumbar
puncture), and receive treatment in the hospital
with appropriate intravenous antimicrobial
agents.
If the child develops a localized infection,
therapy should be directed toward the likely
pathogens.
Fever of Unknown Origin

The classification of FUO is best reserved
for children with fever documented by a
health care provider and for which the cause
could not be identified after 3 wk of
evaluation as an outpatient or after 1 wk of
evaluation in the hospital
We apologize for any inconvenience to the environment.
(Çevreye verdiğimiz rahatsızlık nedeniyle özür dileriz)
SUMMARY OF DEFINITIONS AND MAJOR FEATURES OF
THE FOUR SUBTYPES OF FEVER OF UNKNOWN ORIGIN
FEATURE
CLASSIC FUO
HEALTH CARE–
ASSOCIATED IMMUNE-DEFICIENT FUO HIV-RELATED FUO
FUO
Definition
>38.0°C, >3 wk, ≥38.0°C, >1 wk, not
≥38.0°C, >1 wk, negative
>2 visits or 1 wk in present or incubating
cultures after 48 hr
hospital
on admission
≥38.0°C, >3 wk for
outpatients, >1 wk for
inpatients, HIV infection
confirmed
Patient location
Community, clinic,
Acute care hospital Hospital or clinic
or hospital
Community, clinic, or
hospital
HIV (primary infection),
typical and atypical
Cancer, infections,
Health care–
mycobacteria, CMV,
inflammatory
associated infections, Majority due to infections, but lymphomas,
conditions,
postoperative
cause documented in only 40- toxoplasmosis,
Leading causes
undiagnosed,
complications, drug 60%
cryptococcosis, immune
habitual
reconstitution
fever
hyperthermia
inflammatory syndrome
(IRIS)
FEATURE CLASSIC FUO
History
emphasis
HEALTH
CARE–
ASSOCIATED
FUO
Travel, contacts,
animal and insect
Operations and
exposure,
procedures,
medications,
devices, anatomic
immunizations,
considerations,
family history,
drug treatment
cardiac valve
disorder
Fundi,
oropharynx,
temporal artery,
abdomen, lymph Wounds, drains,
Examination
nodes, spleen,
devices, sinuses,
emphasis
joints, skin, nails, urine
genitalia, rectum
or prostate, lower
limb deep veins
IMMUNE-DEFICIENT
FUO
HIV-RELATED
FUO
Stage of chemotherapy,
drugs administered,
underlying
immunosuppressive
disorder
Drugs, exposures, risk
factors, travel,
contacts, stage of
HIV infection
Skin folds, IV sites, lungs,
perianal area
Mouth, sinuses, skin,
lymph nodes, eyes,
lungs, perianal area
FUO Etiology





The many causes of FUO in children are infections and
rheumatologic (connective tissue or autoimmune) diseases .
Neoplastic disorders should also be seriously considered,
although most children with malignancies do not have fever
alone.
The possibility of drug fever should be considered if the
patient is receiving any drug.
Drug fever is usually sustained and not associated with other
symptoms.
Discontinuation of the drug is associated with resolution of
the fever, generally within 72 hr, although certain drugs, such
as iodides, are excreted for a prolonged period with fever that
can persist for as long as 1 mo after drug withdrawal.


Most fevers of unknown or unrecognized origin
result from atypical presentations of common
diseases.
In some cases, the presentation as an FUO is
characteristic of the disease, such as juvenile
idiopathic arthritis, but the definitive diagnosis can
be established only after prolonged observation
because initially there are no associated or specific
findings on physical examination and all laboratory
results are negative or normal.


In general, the systemic infectious diseases most
commonly implicated in children with FUO are
salmonellosis, tuberculosis, rickettsial diseases,
syphilis, Lyme disease, cat-scratch disease, atypical
prolonged presentations of common viral diseases,
infectious mononucleosis, cytomegalovirus (CMV)
infection, viral hepatitis, coccidioidomycosis,
histoplasmosis, malaria, and toxoplasmosis.
Less common infectious causes of FUO include
tularemia, brucellosis, leptospirosis, and rat-bite fever.
AIDS alone is not usually responsible for FUO,
although febrile illnesses often occur in patients with
AIDS as a result of opportunistic infections



Juvenile idiopathic arthritis (JIA) and systemic lupus
erythematosus (SLE) are the connective tissue diseases
associated most commonly with FUO.
Inflammatory bowel disease, rheumatic fever, and
Kawasaki disease are also commonly reported as
causes of FUO.
If factitious fever (inoculation of pyogenic material or
manipulation of the thermometer by the patient or
parent) is suspected, the presence and pattern of fever
should be documented in the hospital.


Prolonged and continuous observation, which
can include electronic or video surveillance, of
patients is imperative. FUO lasting >6 mo is
uncommon in children and suggests
granulomatous or autoimmune disease.
Repeat interval evaluation, including history,
physical examination, laboratory evaluation, and
roentgenographic studies is required.
Diagnosis

The evaluation of FUO requires a thorough
history and physical examination supplemented
by a few screening laboratory tests and
additional laboratory and radiographic tests as
indicated by the history or abnormalities on
examination or initial screening.
History


The age of the patient is helpful in evaluating
FUO.
Children >6 yr of age often have a respiratory or
genitourinary tract infection, localized infection
(abscess, osteomyelitis), JIA, or, rarely, leukemia.
Adolescent patients are more likely to have
tuberculosis, inflammatory bowel disease,
autoimmune processes, or lymphoma, in
addition to the causes of FUO found in younger
children.



A history of unusual dietary habits or travel as early
as the birth of the child should be sought.
Malaria, histoplasmosis, and coccidioidomycosis
can re-emerge years after visiting or living in an
endemic area.
It is important to identify prophylactic
immunizations and precautions taken by the patient
against ingestion of contaminated water or food
during foreign travel.


A medication history should be pursued
rigorously.
This history should elicit information about
over-the-counter preparations and topical
agents, including eye drops, that may be
associated with atropine-induced fever.


The genetic background of a patient also is important.
Ancestry from the Mediterranean should suggest the
possibility of familial Mediterranean fever (FMF).
Both FMF and hyperimmunoglobulin D syndrome are
inherited as autosomal-recessive disorders.
Tumor necrosis factor receptor–associated periodic
syndrome (TRAPS) and Muckle-Wells syndrome are
inherited as autosomal dominant traits.
Physical examination




A complete is essential to find any physical clues
to the underlying diagnosis.
The child's general appearance, including sweating
during fever, should be noted.
The continuing absence of sweat in the presence
of an elevated or changing body temperature
suggests dehydration due to vomiting, diarrhea, or
central or nephrogenic diabetes insipidus.
It also should suggest anhidrotic ectodermal
dysplasia, familial dysautonomia, or exposure to
atropine.
EXAMPLES OF SUBTLE PHYSICAL FINDINGS HAVING SPECIAL
SIGNIFICANCE IN PATIENTS WITH FEVER OF UNKNOWN ORIGIN
BODY SITE
PHYSICAL FINDING
DIAGNOSIS
Head
Sinus tenderness
Sinusitis
Temporal artery
Nodules, reduced pulsations
Temporal arteritis
Ulceration
Disseminated histoplasmosis
Tender tooth
Periapical abscess
Choroid tubercle
Disseminated granulomatosis*
Petechiae, Roth's spot
Endocarditis
Thyroid
Enlargement, tenderness
Thyroiditis
Heart
Murmur
Infective or marantic endocarditis
Abdomen
Enlarged iliac crest lymph nodes,
splenomegaly
Lymphoma, endocarditis,
disseminated granulomatosis*
Perirectal fluctuance, tenderness
Abscess
Prostatic tenderness, fluctuance
Abscess
Testicular nodule
Periarteritis nodosa
Epididymal nodule
Disseminated granulomatosis
Lower extremities
Deep venous tenderness
Thrombosis or thrombophlebitis
Skin and nails
Petechiae, splinter hemorrhages,
subcutaneous nodules, clubbing
Vasculitis, endocarditis
Oropharynx
Fundi or conjunctivae
Rectum
Genitalia


A careful ophthalmic examination is important. Red,
weeping eyes may be a sign of connective tissue
disease, particularly polyarteritis nodosa.
Palpebral conjunctivitis in a febrile patient may be a
clue to measles, coxsackievirus infection,
tuberculosis, infectious mononucleosis,
lymphogranuloma venereum, and cat-scratch disease.
In contrast, bulbar conjunctivitis in a child with FUO
suggests Kawasaki disease or leptospirosis.




Petechial conjunctival hemorrhages suggest
infective endocarditis.
Uveitis suggests sarcoidosis, JIA, SLE, Kawasaki
disease, Behçet disease, and vasculitis.
Chorioretinitis suggests CMV, toxoplasmosis,
and syphilis.
Proptosis suggests an orbital tumor,
thyrotoxicosis, metastasis (neuroblastoma),
orbital infection, Wegener granulomatosis, or
pseudotumor.


The ophthalmoscope should also be used to
examine nailfold capillary abnormalities that are
associated with connective tissue diseases such
as juvenile dermatomyositis and systemic
scleroderma.
Immersion oil or lubricating jelly is placed on
the skin adjacent to the nailbed, and the capillary
pattern is observed with the ophthalmoscope set
on +40.





FUO is sometimes caused by hypothalamic dysfunction.
A clue to this disorder is failure of pupillary constriction
due to absence of the sphincter constrictor muscle of the
eye.
This muscle develops embryologically when hypothalamic
structure and function also are undergoing differentiation.
Fever resulting from familial dysautonomia may be
suggested by lack of tears, an absent corneal reflex, or a
smooth tongue with absence of fungiform papillae.
Tenderness to tapping over the sinuses or the upper teeth
suggests sinusitis. Recurrent oral candidiasis may be a clue
to various disorders of the immune system.




Fever blisters are common findings in patients with
pneumococcal, streptococcal, malarial, and rickettsial
infection.
These lesions also are common in children with
meningococcal meningitis (which usually does not
manifest as FUO) but rarely are seen in children with
meningococcemia.
Fever blisters also are occasionally seen with Salmonella
or staphylococcal infections.
Hyperemia of the pharynx, with or without exudate,
suggests infectious mononucleosis, CMV infection,
toxoplasmosis, salmonellosis, tularemia, Kawasaki
disease, or leptospirosis.





The muscles and bones should be palpated carefully. Point
tenderness over a bone can suggest occult osteomyelitis or
bone marrow invasion from neoplastic disease.
Tenderness over the trapezius muscle may be a clue to
subdiaphragmatic abscess.
Generalized muscle tenderness suggests dermatomyositis,
trichinosis, polyarteritis, Kawasaki disease, or mycoplasmal
or arboviral infection.
Rectal examination can reveal perirectal lymphadenopathy or
tenderness, which suggests a deep pelvic abscess, iliac
adenitis, or pelvic osteomyelitis.
A guaiac test should be obtained; occult blood loss can
suggest granulomatous colitis or ulcerative colitis as the cause
of FUO.



Repetitive chills and temperature spikes are
common in children with septicemia (regardless
of cause), particularly when associated with
kidney disease, liver or biliary disease, infective
endocarditis, malaria, brucellosis, rat-bite fever,
or a loculated collection of pus.
The general activity of the patient and the
presence or absence of rashes should be noted.
Hyperactive deep tendon reflexes can suggest
thyrotoxicosis as the cause of FUO.


The laboratory evaluation of the child with FUO and
whether the evaluation will occur in the inpatient or
outpatient realm are determined on a case-by-case
basis.
Hospitalization may be required for laboratory or
radiographic studies that are unavailable or impractical
in an ambulatory setting, for more-careful
observation, or for temporary relief of parents’
anxiety.



The tempo of diagnostic evaluation should be
adjusted to the tempo of the illness; haste may be
imperative in a critically ill patient, but if the illness is
more chronic, the evaluation can proceed in
systematic fashion and can be carried out in an
outpatient setting.
If there are no clues in the patient's history or on
physical examination that suggest a specific infection
or area of suspicion, it is unlikely that diagnostic
studies will be helpful.
In that common scenario, continued surveillance and
repeated re-evaluations of the child should be
employed to detect any new clinical findings.



Although ordering a large number of diagnostic tests
in every child with FUO according to a predetermined
list is discouraged, certain studies should be
considered in the evaluation.
A complete blood cell count with a differential white
blood cell count and a urinalysis should be part of the
initial laboratory evaluation.
An absolute neutrophil count of <5,000/µL is
evidence against indolent bacterial infection other
than typhoid fever.


Conversely, in patients with a
polymorphonuclear leukocyte count of
>10,000/µL or a nonsegmented
polymorphonuclear leukocyte count of
>500/µL a severe bacterial infection is highly
likely.
Direct examination of the blood smear with
Giemsa or Wright stain can reveal organisms of
malaria, trypanosomiasis, babesiosis, or relapsing
fever.
ESR



An erythrocyte sedimentation rate (ESR) of >30
mm/hr indicates inflammation and the need for
further evaluation for infectious, autoimmune, or
malignant diseases.
An ESR of >100 mm/hr suggests tuberculosis,
Kawasaki disease, malignancy, or autoimmune disease.
A low ESR does not eliminate the possibility of
infection or JIA.
CRP


C-reactive protein is another acute-phase
reactant that becomes elevated and returns to
normal more rapidly than the ESR.
Experts may prefer to check 1 of the 2 because
there is no evidence that measuring both the
ESR and C-reactive protein in the same patient
with FUO is clinically useful.






Blood cultures should be obtained aerobically.
Anaerobic blood cultures have an extremely low yield
and should be obtained only if there are specific
reasons to suspect anaerobic infection.
Multiple or repeated blood cultures may be required
to detect bacteremia associated with infective
endocarditis, osteomyelitis, or deep-seated abscesses.
Polymicrobial bacteremia suggests factitious selfinduced infection or gastrointestinal (GI) pathology.
The isolation of leptospires, Francisella, or Yersinia can
require selective media or specific conditions not
routinely used.
Urine culture should be obtained routinely.



Tuberculin skin testing should be performed
with intradermal placement of 5 units of purified
protein derivative (PPD) that has been kept
appropriately refrigerated.
Radiographic examination of the chest, sinuses,
mastoids, or GI tract may be indicated by
specific historical or physical findings.
Radiographic evaluation of the GI tract for
inflammatory bowel disease may be helpful in
evaluating selected children with FUO and no
other localizing signs or symptoms.


Examination of the bone marrow can reveal
leukemia; metastatic neoplasm; mycobacterial,
fungal, or parasitic diseases; and histiocytosis,
hemophagocytosis, or storage diseases.
If a bone marrow aspirate is performed, cultures
for bacteria, mycobacteria, and fungi should be
obtained.


Serologic tests can aid in the diagnosis of infectious
mononucleosis, CMV infection, toxoplasmosis,
salmonellosis, tularemia, brucellosis, leptospirosis,
cat-scratch disease, Lyme disease, rickettsial disease,
and, on some occasions, JIA.
The clinician should be aware that the reliability
and sensitivity and specificity of these tests vary;
for instance, serologic tests for Lyme disease
outside of reference laboratories have been
generally unreliable.




Radionuclide scans may be helpful in detecting abdominal
abscesses as well as osteomyelitis, especially if the focus
cannot be localized to a specific limb or multifocal disease
is suspected. Gallium citrate (67Ga) localizes
inflammatory tissues (leukocytes) associated with tumors
or abscesses.
99mTc phosphate is useful for detecting osteomyelitis
before plain roentgenograms demonstrate bone lesions.
Granulocytes tagged with indium (111In) or iodinated IgG
may be useful in detecting localized pyogenic processes.
18F-fluorodeoxyglucose positron emission tomography
(FDG-PET) is a helpful imaging modality in adults with an
FUO and can contribute to an ultimate diagnosis in 30-60%
of patients.


Echocardiograms can demonstrate the presence
of a vegetation on the leaflets of heart valves,
suggesting infective endocarditis.
Ultrasonography can identify intra-abdominal
abscesses of the liver, subphrenic space, pelvis,
or spleen.


Total body CT or MRI (both with contrast)
permits detection of neoplasms and collections
of purulent material without the use of surgical
exploration or radioisotopes.
CT and MRI are helpful in identifying lesions of
the head, neck, chest, retroperitoneal spaces,
liver, spleen, intra-abdominal and intrathoracic
lymph nodes, kidneys, pelvis, and mediastinum.



CT or ultrasound-guided aspiration or biopsy of
suspicious lesions has reduced the need for
exploratory laparotomy or thoracotomy.
MRI is particularly useful for detecting
osteomyelitis if there is concern about a specific
limb.
Diagnostic imaging can be very helpful in
confirming or evaluating a suspected diagnosis
but rarely leads to an unsuspected cause, and in
the case of CT scans, the child is exposed to
large amounts of radiation.



Biopsy is occasionally helpful in establishing a
diagnosis of FUO.
Bronchoscopy, laparoscopy, mediastinoscopy,
and GI endoscopy can provide direct
visualization and biopsy material when organspecific manifestations are present.
When employing any of the more-invasive
testing, the risk:benefit ratio for the patient must
always be taken into consideration before
proceeding further.



The ultimate treatment of FUO is tailored to the
underlying diagnosis.
Fever and infection in children are not
synonymous; antimicrobial agents should not be
used as antipyretics, and empirical trials of
medication should generally be avoided.
An exception may be the use of antituberculous
treatment in critically ill children with suspected
disseminated tuberculosis.


Empirical trials of other antimicrobial agents
may be dangerous and can obscure the diagnosis
of infective endocarditis, meningitis,
parameningeal infection, or osteomyelitis.
After a complete evaluation, antipyretics may be
indicated to control fever and relieve symptoms.
Prognosis





Children with FUO have a better prognosis than
do adults.
The outcome in a child depends on the primary
disease process, which is usually an atypical
presentation of a common childhood illness.
In many cases, no diagnosis can be established and
fever abates spontaneously.
In as many as 25% of cases in whom fever persists,
the cause of the fever remains unclear, even after
thorough evaluation.
FEATURE CLASSIC FUO
Imaging,
Investigation biopsies,
sedimentation
emphasis
rate, skin tests
Observation,
outpatient
temperature
chart,
Management
investigations,
avoidance of
empirical drug
treatments
Time course
Months
of disease
Tempo of
Weeks
investigation
HEALTH
CARE–
ASSOCIATED
FUO
IMMUNE-DEFICIENT
FUO
HIV-RELATED
FUO
Imaging, bacterial
CXR, bacterial cultures
cultures
Blood and lymphocyte
count; serologic tests;
CXR; stool
examination; biopsies
of lung, bone marrow,
and liver for cultures
and cytologic tests;
brain imaging
Depends on
situation
Antimicrobial treatment
protocols
Antiviral and
antimicrobial
protocols, vaccines,
revision of treatment
regimens, good
nutrition
Weeks
Days
Weeks to months
Days
Hours
Days to weeks