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TESTING FOR PATIENTS WITH
FEVER OF UNKNOWN ORIGIN
What does fever of unknown origin mean?
This is a term that is generally used to refer to a persistent fever of greater than 39.7 °C, for
which the underlying cause is not readily evident.
What might be the underlying cause of such a fever?
Causes of fever are numerous. Possibilities include viral, bacterial, parasitic and fungal
infections. Immune-mediated diseases such as immune-mediated polyarthritis and lupus may
include fever as a clinical sign. Various neoplastic diseases (tumors) and reactions to some
drugs may cause fever. Inflammation or infection of organs in the abdomen or chest can also
be associated with fever.
Given the many possibilities, how can we determine the underlying cause in my
pet?
A thorough history and physical examination may provide some initial 'clues'. A history of travel
to certain geographical locations may increase the index of suspicion for fungal or parasitic
infections. A cat with a history of recent fighting or exposure to other unvaccinated cats may
increase the possibility of underlying viral infection with feline leukemia or feline
immunodeficiency virus.
Some conditions are more likely in each species. For example, in cats, viral infections are
common causes of persistent fever. In dogs, localized areas of persistent bacterial infection
such as in the heart valves, and immune-mediated disorders are more frequent causes of
recurrent fever.
Physical examination may reveal the presence of enlarged
lymph nodes or other organs, suggesting these sites as a
possible focus of inflammation, infection or tumors.
Often the cause of the fever is not obvious. In this instance a
series of screening tests including a complete blood count
(CBC), a serum biochemistry profile, and a urinalysis is
recommended.
What might these screening tests indicate?
From: Laboratory Urinalysis and Hematology
by Carolyn Sink
Published by Teton NewMedia2004
with permission
The complete blood count (CBC) provides us with an
evaluation of the red blood cells, white blood cells, and the
platelet components of a blood sample. This numerical analysis is accompanied by a
microscopic evaluation of these cells on a blood smear.
Anemia is indicated by decreases in total red blood cell numbers, hemoglobin, and the packed
cell volume (PCV) of the blood sample. The mechanism of anemia and therefore the underlying
cause of the fever may be suggested by an evaluation of the blood smear. For example
immune-mediated destruction of red blood cells may be evident, or the presence of blood
parasites such as Mycoplasma hemofelis may be confirmed.
Bacterial and fungal infections and inflammatory conditions are usually accompanied by
increases in the white blood cell numbers. The magnitude of increase and the proportions of
the different white blood cells that are increased may provide us with an estimation of the
duration and severity of the underlying infection or inflammation. Viral infections may be
associated with decreases in the white blood cell numbers. The presence of atypical or unusual
white blood cells would suggest the possibility of underlying bone marrow disease.
The serum biochemistry profile provides us with an evaluation
of many organs including the liver, pancreas and kidneys.
Infections or inflammation of these organs may be accompanied
by increases in enzymes that are specific for the organ. For
example, inflammation of the pancreas is often associated with
increases in the pancreatic enzymes amylase and lipase.
Increases in the liver related enzymes ALT (alanine
aminotransferase), ALP (alkaline phosphatase) and GGT
(gamma glutamyltransferase) may be associated with underlying
liver disease.
Infections are often accompanied by increases in proteins
(globulins) produced by specific cells (lymphocytes) of the
immune system. The biochemistry profile can determine the total
amount of globulin present in a sample. Significant increases in globulins may warrant further
investigation; this will be discussed later.
A urinalysis provides an evaluation of the chemical and physical properties of a urine sample.
Infections of the urinary and genital tract may be accompanied by large numbers of red blood
cells and white blood cells in a urine sample. Occasionally the specific agent (bacterial or
fungal) will also be evident in a urine sample.
What additional tests might be indicated for the evaluation of fever of unknown
origin?
Any additional testing depends entirely on the combined
results of the history, physical examination, and
screening tests. It is impossible to list all possible
additional tests. However, here are a few examples of
common additional tests.
If the initial screening tests indicate a problem with an
organ such as the liver or kidneys, or the presence of a
tumor, then imaging studies (radiography or ultrasound)
of these organs or masses may be suggested, along
with fine needle aspiration biopsy or tissue biopsy in
order to determine what cell types are present.
Large increases in globulins detected with the serum biochemistry profile may indicate the need
for a serum protein electrophoresis. This test will help us to decide if the increase in these
serum proteins is due to inflammation or due to underlying malignancy.
An animal with clinical signs of lameness may need to undergo joint taps. This procedure
involves removing a small amount of joint fluid using a sterile needle. The joint fluid is then
spread onto a microscope slide and examined for evidence of inflammation, abnormal cells,
and bacterial and fungal organisms by a veterinary pathologist. This fluid may also be sent to a
veterinary referral laboratory for bacterial or fungal culture, as these organisms may be present
in such low numbers that they are not readily seen on the slides.
An animal with clinical signs of respiratory disease may need to undergo diagnostic procedures
such as a transtracheal wash or bronchoalveolar lavage, which aim to retrieve diagnostic
material from the airways for evaluation and culture.
Animals with evidence of neurological disease (seizures,
balancing) may need to have a cerebrospinal fluid tap. This
anesthetic and the removal of a small amount of spinal fluid
pathologist. Culture of this fluid for the presence of bacterial or
indicated.
severe depression, difficulty
procedure involves a general
for evaluation by a veterinary
fungal organisms may also be
In cats, blood testing for feline leukemia virus and feline immunodeficiency virus are strongly
recommended. It is important to rule out these viruses as an underlying cause of fever in this
species. In dogs, blood testing for other organisms such as lyme disease, or systemic fungal
disease may be performed if the clinical signs and screening tests suggest the possibility of
such an infection.

This client information sheet is based on material written by Kristiina Ruotsalo, DVM, DVSc, Dip ACVP &
Margo S. Tant BSc, DVM, DVSc.
© Copyright 2004 Lifelearn Inc. Used with permission under license. February 12, 2016