Cracking Fevers Of Unknown Origin

Getting to the bottom of an unexplained illness can mean a multitude of tests, lots of time and a huge bill. In some cases, the mystery is never solved.

Fever can indicate infectious, inflammatory, immune-mediated or neoplastic disease. Typically, a physical examination and medical history lead a practitioner to a fever’s cause. Or the fever resolves serendipitously or in response to antibiotic therapy.

But in some cases, the underlying cause of the fever is not readily apparent. These patients are said to have a fever of unknown origin (FUO).

In 1961, the acronym FUO was coined by medical doctors Robert Petersdorf and Paul Beeson and defined as a temperature greater than 101 degrees Fahrenheit on several occasions, illness for more than three weeks and failure to reach a diagnosis despite one week of inpatient investigation.

According to the Merck Veterinary Manual and veterinary specialists, this syndrome has no recognized definition in veterinary medicine, making its prevalence difficult to determine.

“FUO is common in both species [canine and feline], although underlying causes can be quite different,” says Craig Webb, DVM, Dipl. ACVIM, Ph.D., MS.

“Unfortunately, these cases often require that we try to rule out almost everything,” continues Webb, an associate professor of internal medicine at Colorado State University’s College of Veterinary Medicine and Biomedical Sciences. “So after the history and physical examination we start with basic blood work and urinalysis, fecal exam, ELISA, serology and PCR for infectious disease agents, basic and advanced imaging, as well as cultures of urine, joint fluid, blood, bile, even CSF.”

Specialists say they start testing from the most to the least common potential causes, checking the results before moving to the next possibility. They say clients must be told up front that the investigation is not easy or cheap. The cost in the most difficult cases can easily run into the thousands of dollars.

The Long Haul

“All tests have a price tag,” says Steven Marks, BVSc., MS, MRCVS, Dipl. ACVIM. “My basic estimate for working up a fever of unknown origin is $1,500 to $2,500. This is to get started. It could be more, it could be less. Most of our FUO cases take a long time to answer and include hospital admission.”

A recent FUO case surgically treated by Dr. Marks, a clinical associate professor at the North Carolina State University College of Veterinary Medicine, involved a lodged foreign body.

“The dog presented with a fever,” Marks says. “We found that a stick lodged in the dog’s esophagus had migrated through its chest wall. It underwent surgery and the repairs were made with a favorable outcome.

“More often,” he adds, “when a disease is subtle it is difficult to find, and when it is obvious it’s too far gone to treat. You also need to be fortunate enough to have to have the owners’ approval for testing and treatment.”

Vaccines and Diseases

Knowing a dog or cat's vaccine history can help rule out some fever-causing diseases. In some cases, an administered  vaccine can be the cause, especially in younger dogs or cats vaccinated within the previous month. A lot of diseases that have a vaccine can cause a fever as well.

“In cats, retroviruses, feline panleukopenia and feline leukemia can cause a fever, while tick-borne diseases in dogs can also cause a fever,” Marks says. “Other canine diseases like parvo can cause fever, but there are other obvious symptoms that guide vets to the diagnosis, unlike leptospirosis or Lyme disease.”

In FUO cases, veterinarians can feel as though they’re starring on the TV show “House,” considering a diagnosis only to find it wasn’t the fever’s cause after consulting with other practitioners. Identifying an FUO’s cause is like solving a mystery.

“Often, neurologic conditions are coupled with symptoms in addition to the fever, like a head tilt, balance, pain and vision—but not always,” says Daniel Fletcher, DVM, Ph.D., Dipl. ACVECC, an assistant professor of emergency and critical care at Cornell University.

Two Types of Fever

A dog’s normal body temperature is 101.5 degrees Fahrenheit, and a temperature above 103 is cause for concern, veterinarians say. But most will not administer counteracting drugs to treat the symptom until the temperature reaches 106.

“At 107 degrees or higher, an animal is at risk for disseminated intravascular coagulation (DIC), brain and or heart damage,” says Julie Byron, DVM, MS, Dipl. ACVIM, an assistant professor at Ohio State University. “At that point, veterinarians need to step in to reduce the fever regardless of the pending diagnosis. Keep in mind, the determination needs to be made if the animal is experiencing a true fever or hyperthermia.”

In cases of hyperthermia, heat stroke or severe anxiety can cause an animal to have a seizure, experts say. When an environmental factor is suspected to be the fever’s cause, taking steps to cool the patient may be the only medical action needed, veterinarians say.

“A true fever is caused by the hypothalamus in the brain telling the body that its temperature needs to be higher,” Marks says. “It is pretty controversial to treat a fever without knowing what is causing it. The route to a diagnosis can be determined through medical history and/or other presenting symptoms.”

Some basic treatments, however, can make the patient feel more comfortable.

What to Do

Intravenous fluids are most often the first line of treatment unless the patient has a known heart condition, Webb says.

“We hope to delay more specific treatments until we’ve performed as many diagnostic tests as needed or we identify the most likely cause,” he says. “Bacterial infections are treated with antibiotics, immune-mediated diseases with immunomodulatory drugs, cancer with chemotherapeutics, etc.”

Administering drugs to reduce the fever can cause more harm than good, Dr. Byron says.

“Giving a febrile animal a steroid when it has an infectious disease can make its condition worse,” she points out. “If steroids are given to an animal with cancer, it can mask the ability to make a cancer diagnosis.”

Common FUO Causes

The big categories of rule-outs for FUO are infectious, inflammatory, immune-mediated, neoplasia and drugs/toxins, Webb says.

Dogs found to have a fever typically present as lethargic, having a decreased appetite, changes in mentation and panting. Feline symptoms include vomiting, diarrhea or hiding.

“Cats are good about going along with their lives when they’re actually pretty sick,” Dr. Fletcher says. “A veterinarian’s goal is to find the cause when the disease is subtle.”

Owner Information

Questioning the owner can be very important in making a diagnosis, specialists say. Information about the animal’s diet, environment, exposure to other animals and their relationship with the pet can play a role in the final diagnosis. Sometimes, though, veterinarians need to dig deeper.

“A veterinarian might ask the owner if the pet lives inside or outdoors, and they’ll be quick to say indoors, forgetting that the cat, for example, snuck out for a few days last week,” Byron says. “Cats can be pretty vicious for as small as they are. If a cat was in a fight with another cat, it might have a well-hidden abscess that has not ruptured. These abscesses can hide from the owner and a veterinarian—under the tail or under an armpit. Since they haven’t ruptured, fur hides the healed-over wound, and there isn’t blood to give it away.”

Marks adds that finding the underlying disease causing a fever when symptoms are minimal not only means faster treatment but better outcomes.

“Unfortunately, it is frequently the case that we never discover what is actually causing the fever,” he says. “We treat with supportive care, or beyond that we make an educated guess and treat with more specific therapy and hope we’re right. Sometimes, even when we treat with a specific drug and the fever resolves, we can’t be sure it was the drug that did the trick and not just time and Mother Nature.”

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