A practical approach to a fever of unknown origin

When a patient has a fever of unknown origin (FUO), both clients and clinicians may become frustrated searching for a diagnosis. To assist veterinary professionals, a practical approach to the diagnosis of FUOs was discussed by Stuart Walton, BVSc, MANZCVS, DACVIM, clinical assistant professor at the University of Florida, in a session at the 2023 Fetch dvm360® conference in Charlotte, North Carolina.

Causes of FUO

Walton cautioned attendees that the term FUO is often overused in practice. FUO should not be applied to a higher body temperature identified at a single time point. A true FUO is a persistent elevation of body temperature over a period of weeks or months. It may wax and wane over this period. He noted that when searching for a cause, it is important to remember that the fever is a clinical sign and is usually an "uncommon manifestation of a common disease."

The most common causes vary by species and age and include the following:

• Infectious Disease
• Immune-Mediated Disease
• Noninfectious Inflammatory Conditions
• Neoplasia
• Drug reactions
• Idiopathic pyrexia

When working to narrow the differential diagnosis list, "a thorough history is everything," said Walton. This should include vaccinations, medications, previous medical diagnoses and comorbidities, prior surgeries, travel, environment, and contact with other animals. Combining this information with signalment, especially age and breed, can help to guide the diagnostic workup.

The diagnostic workup

Setting appropriate client expectations is essential when embarking on a workup for FUO. Walton shared that on average, obtaining a diagnosis requires 10 procedures per dog. Owners must be prepared to make both a financial and time commitment. Patience is essential as a diagnosis often takes days or weeks to achieve, and some tests will need to be repeated over time.

"The most important thing is going back to basics," said Walton. "Get a good history and do a good physical examination.”

Identifying risk factors in the history and abnormalities on physical examination will help to focus diagnostic testing. The physical examination should include comprehensive rectal, fundic, orthopedic, and neurologic evaluations. Sometimes, repeating the physical examination throughout a 24-hour period of hospitalization can help to detect subtle changes that may wax and wane, such as intermittent pain or swelling.

Walton recommended beginning testing with safe, simple, and inexpensive tests. A CBC with a blood smear, chemistry panel, and urinalysis help to evaluate systemic wellness. Changes may be present but are often nonspecific. "Imaging will find abnormalities but not give a diagnosis," says Walton, whose "diagnostic test of choice will always be aspirates."

Ultimately, cytopathology and histopathology are the tests that most often provide a definitive diagnosis. Other tests, such as imaging, are needed to determine what tissues or fluids need to be collected for evaluation. Walton encouraged general practitioners to do diagnostics, stating that many tests can be done in general practice, including arthrocentesis, CSF taps, and ultrasound-guided aspiration of organs. "The thing that stops us from doing a lot of tests in practice is fear," he stated.

Many tests are available to identify an infectious cause of FUO, but Walton said that clinicians do not need to run every available test. Instead, select tests that are most likely to provide helpful information. For instance, antigen testing for particular organisms has good sensitivity when the organism is present. Antibody testing at a single time point is not very helpful as it does not confirm active infection. Blood cultures often have a low diagnostic yield, but about 80% of the organisms grown show antimicrobial resistance, which can be valuable information.

The goal of the diagnostic workup is to identify an underlying disease process. This will allow the veterinarian to develop a treatment plan that treats the cause of the fever and not just the symptom.

Treatment considerations

Although it is tempting to treat the fever before obtaining a definitive diagnosis, Walton reminded veterinarians that a fever is a protective mechanism for the body. Additionally, treating without a diagnosis may confound some test results and make a definitive diagnosis more difficult to obtain.

Low grade fevers may not require treatment if the pet is otherwise well. For high grade fevers, hospitalization may be required for treatment. In cases where a diagnosis is not obtained, empirical therapy can be considered. Discuss the risks and benefits of a therapeutic trial with the owners and monitor the patient carefully.

Walton also reminded veterinarians that when prescribing antibiotics, an appropriate dose and duration should be used. Drug choice should consider location of the infection and penetration into that area of the body.

Take home points

Obtaining a definitive diagnosis for a FUO requires time, patience, and often numerous tests. Test selection should be guided by careful evaluation of signalment, a detailed history, and thorough and repeated physical examinations.

Reference

Walton S. Fever of unknown origin. Presented at: Fetch dvm360 Conference; March 24-26, 2023. Charlotte, NC.