What does fever of unknown origin mean?
Fever of unknown origin is a term that is generally used to refer to a persistent fever of greater than 39.7 °C (103.5 °F) 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 you determine the underlying cause in my pet?
The search for answers begins with a thorough history and physical examination. 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 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.
"With a fever of unknown origin, the cause of the fever is not obvious."
With a fever of unknown origin, the cause of the fever is not obvious. In this instance, a series of screening tests including a complete blood count , a serum biochemistry profile, and a urinalysis is recommended.
What might these screening tests indicate?
The complete blood count (CBC) provides us with an evaluation of the different cell types in the blood. These are red blood cells, which carry oxygen to the tissues, white blood cells, which fight infection and respond to inflammation and the platelets, which help the blood to clot. The CBC provided details about the number, size, and shape of the various cell types, and identifies the presence of abnormal cells on a blood smear. See handout “Complete Blood Count” for further information.
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 your veterinarian 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. See handout “Serum Biochemistry” for further information.
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. A urinalysis is essential for the accurate interpretation of changes noted on the serum biochemistry profile. These two screening tests should always accompany one another and be taken at the same time. See handout “Urinalysis” for further information.
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, examples of common additional tests are provided below.
"Any additional testing depends entirely on the combined results of the history, physical examination, and screening 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, such as radiography (X-rays) or ultrasound of these organs or masses may be suggested, along with fine needle aspiration 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 cancer.
A pet 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 sent to a veterinary pathologist, who will examine the slide for evidence of inflammation, abnormal cells, and bacterial and fungal organisms.
The fluid sample 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.
A pet 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, severe depression, or difficulty balancing) may need to have a cerebrospinal fluid tap. This procedure involves a general anesthetic and the removal of a small amount of spinal fluid for evaluation by a veterinary pathologist. Culture of this fluid for the presence of bacterial or fungal organisms may also be indicated.
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.
