Pyrexia of unknown origin (PUO) in dogs and cats
What is pyrexia of unknown origin?
Pyrexia is the medical term for fever, referring to a rise in the core body temperature. In dogs and cats, a true fever is a temperature ranging between 39.5°C and 41.1°C. A fever is not a disease; rather, it is the body’s response to a threat. It may be a sign of infection, inflammation, immune-mediated disease or even cancer. An elevated temperature will enhance the body’s immune system response to the threat and reduce the rapid division of bacteria.
Pyrexia of unknown origin (PUO), also termed fever of unknown origin (FUO), refers to a fever for which the cause is not apparent, even after extensive attempts at diagnosis. The term is used liberally in veterinary medicine. It should be used to describe a fever that does not resolve spontaneously, that does not respond to antibiotics, that continues or keeps reoccurring, and for which the cause remains uncertain after diagnostic testing.
Body temperature is regulated by an area of the brain called the hypothalamus. The hypothalamus acts as a thermostat to maintain the body’s temperature as close to normal as possible, by regulating the body’s heat production, heat loss, and heat gain. In a true fever, the thermostat is reset to a higher temperature.
Temperatures of less than 41.1 are not likely to be harmful and may in fact be beneficial because they are in fact a protective response to inflammation. If the body temperature rises above 41.1°C, or if the elevated temperature continues for a prolonged period, serious consequences such as organ failure can result, and medical treatment is required. Cats are less likely than dogs to succumb to the dangerous effects of body temperatures greater than 41.1.
Symptoms of pyrexia of unknown origin in dogs and cats
The symptoms of a fever include:
- High body temperature
- Decreased appetite
- Rapid heart rate
- Decreased body fluids/dehydration
- Increased respiratory rate
- Other symptoms depending upon the underlying cause
Causes of pyrexia of unknown origin in dogs and cats
By definition, the cause of pyrexia of unknown origin (PUO) in dogs and cats remains unidentified. While the diagnostic workup can be challenging, in most cases of a fever, a cause can eventually be determined; infection is the most common cause. In a small percentage of animals, the fever continues or keeps coming back and the cause cannot be determined; this is a true PUO. However, most PUOs are caused by a common disease presenting in an obscure fashion.
Some of the typical causes of PUO’s in dogs and cats include:
- Infections (most commonly, bacterial, viral, parasites, and other microorganisms)
- Immune-mediated diseases (rare in cats)
- Metabolic diseases
- Endocrine diseases
- Miscellaneous inflammatory conditions
- Various drugs
- Various toxins
Fevers are common in cats, and most diseases associated with PUO in cats are infectious. It is estimated that about 10% to 15% of PUOs in both dogs and cats remain undiagnosed despite thorough diagnostic investigation.
As per research papers from vetfolio.com, here are some of the common causes for dogs and cats:
Potential causes of fever of unknown origin in dogs (Source: Vetfolio)
- Bacterial infection (focal or systemic): Bacteremia, infective endocarditis, septic arthritis,
osteomyelitis, diskospondylitis, septic meningitis, pyothorax, pyelonephritis, prostatitis, stump
pyometra, peritonitis, deep pyoderma, abscess
- Bacterial diseases: Brucellosis, bartonellosis, borreliosis, leptospirosis, mycoplasmosis (hemotrophic and nonhemotrophic), tuberculosis and other mycobacterial diseases, diseases caused by L-form bacteria (e.g., cellulitis, synovitis)
- Viral: Canine distemper, parvovirus
- Rickettsial: Ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever, salmon poisoning
- Fungal: Histoplasmosis, blastomycosis, cryptococcosis, coccidioidomycosis
- Protozoal: Toxoplasmosis, neosporosis, babesiosis, trypanosomiasis, hepatozoonosis, leishmaniasis
- Immune-mediated diseases: Immunemediated hemolytic anemia, polyarthritis, systemic lupus erythematosus, rheumatoid arthritis, vasculitis, meningitis, steroidresponsive neutropenia and fever
- Neoplastic: Lymphoma, leukemia, multiple myeloma, malignant histiocytosis, necrotic solid tumors
- Noninfectious inflammatory diseases: Lymphadenitis, panniculitis, pansteatitis, panosteitis, pancreatitis, granulomatosis
- Miscellaneous: Portosystemic shunt, drug reaction, toxin, shar-pei fever, metabolic bone disorders, idiopathic causes
Potential causes of fever of unknown origin in cats (Source: Vetfolio)
- Bacterial infection (focal or systemic): Bacteremia, infective endocarditis, septic arthritis, osteomyelitis, diskospondylitis, septic meningitis, pyothorax, pyelonephritis, prostatitis, stump pyometra, peritonitis, abscess
- Bacterial diseases: Bartonellosis, borreliosis(?), mycoplasmosis (hemotrophic and nonhemotrophic), tuberculosis and other mycobacterial diseases, diseases caused by L-form bacteria (e.g., cellulitis or synovitis secondary
to bite wounds or surgical incisions)
- Viral: FeLV, FIV, feline infectious peritonitis, feline calicivirusa
- Rickettsial: Feline ehrlichiosis, anaplasmosis, Rocky Mountain spotted fever
- Fungal: Histoplasmosis, blastomycosis, cryptococcosis, coccidioidomycosis
- Protozoal infections: Toxoplasmosis, cytauxzoonosis, neosporosis(?), babesiosis(?), trypanosomiasis(?)
- Immune-mediated diseases: Polyarthritis, systemic lupus erythematosus, rheumatoid arthritis, vasculitis, meningitis, steroid-responsive neutropenia and fever
- Neoplastic: Lymphoma, leukemia, multiple myeloma, necrotic solid tumors
- Noninfectious inflammatory diseases: Lymphadenitis, panniculitis, pansteatitis, pancreatitis, granulomatosis
- Miscellaneous: Portosystemic shunt, drug reaction, toxin, hyperthyroidism, idiopathic causes
How is pyrexia of unknown origin in dogs and cats diagnosed?
The definitive diagnosis of pyrexia of unknown origin can require considerable time, patience and expense. Investigating the cause of PUO requires a complex history, physical examination, and often laboratory and other diagnostic tests. All potential causes of fever will need to be investigated and ruled out.
Initial diagnostic efforts may include:
- Obtaining a detailed medical history
- Reviewing vaccination status, parasite control, travel history, response to previous medications, indoor/outdoor status and the presence of illness in any cohabiting animals
- Performing a detailed physical examination
- Eye (fundic) and neurologic examinations
- Complete blood tests and blood chemistry profile
- Urinalysis and urine culture
- Chest and abdomen x-rays
- Feline Leukaemia antigen and Feline Immunodeficiency Virus antibody blood tests, for febrile cats
- Trial antibiotics, if bacterial infection is suspected
- Halting all medications, to rule out drug-induced fever
- Investigating stress hyperthermia, common in cats
Further diagnostic testing for PUO in dogs and cats should be targeted to each individual animal, based on the history and physical examination findings, laboratory test results, and the potential causes common to the geographic location.
Further diagnostic testing may include:
- Repetition of some initial tests, particularly the physical examination
- More specialised tests, depending on results of the initial tests
- Tests to specifically investigate the most common known causes of PUO, such as:
- Additional blood tests
- Specialised tests for infectious diseases
- Faecal cultures
- Withdrawal and testing of joint fluid
- An ultrasound of the abdomen, chest, or heart
- Aspiration or biopsies of the bone marrow, lymph nodes, or other tissues to examine the cells of these tissues
- Analysis and bacterial cultures of various body fluids
- X-rays of the bones, joints, or spinal cord
- Computed tomography (CT) or magnetic resonance imaging (MRI)
- Immune panels
- Exploratory surgery
The prognosis for PUO is good where the underlying cause is definitively diagnosed and treated.
The prognosis for undiagnosed PUO in dogs and cats is not known. About 10% to 15% of PUOs in dogs remain undiagnosed despite thorough diagnostic testing. However, a retrospective study revealed that in 13 of 14 dogs with undiagnosed PUO, the fever either resolved spontaneously or responded to drug therapy.
Treatment for pyrexia of unknown origin in dogs and cats
The veterinarian will recommend appropriate treatment on the basis of the final diagnosis. However, in some cases of PUO a specific underlying cause cannot be found, or diagnostic testing is discontinued, and different treatments may be trialled without a definitive diagnosis. Although trial drug therapy can resolve the clinical signs or may confirm a tentative diagnosis, it can also carry significant risk, and careful monitoring is essential.
Medical treatment options include antibiotics, antifungal agents, and anti-inflammatory or immunosuppressive therapy. In many cases, a fever resolves on its own or in response to antibiotic therapy. In some animals, a fever may resolve on the first day of treatment, while others may take weeks or months to fully recover. The animal will need rest until fully recovered to save body energy and avoid exacerbation of symptoms.
The veterinarian will need to decide whether or not to use antipyretic drugs to lower the body temperature. Antipyretics are not always encouraged because the fever can be beneficial, and many believe that antipyretic therapy can have a negative impact on immune responses by causing hypothermia and impairing immune defences. A fever may also increase the effectiveness of antibiotics decrease the virulence of some pathogens. On the negative side, fever can result in significant malaise, loss of energy, dehydration and anorexia (loss of appetite), which can be alleviated with the administration of an antipyretic.
A diet high in nutrition and calories is essential for full recovery. It is normal for the appetite to be affected while the body is feverish. If the animal has no appetite for solids, a high calorie liquid supplement may be prescribed temporarily
Pyrexia, or fever, is common in dogs and cats, being a normal biological response by the body to a bacterial or viral infection or other threat. A fever without any obvious cause is termed a pyrexia of unknown origin (PUO). However, with intensive, repetitive and costly diagnostic testing, a definitive cause for the fever is usually found.
Fever is not a disease itself, but a response to the threat of disease. A fever can be beneficial for a sick animal, as it lowers the rapid division of bacteria and enhances the body’s immune system response. However, fever can lead to loss of appetite, loss of energy, and dehydration. A fever that is too high or goes on for a prolonged period of time needs medical treatment. Therefore, whether animals with PUO will benefit from the use of antipyretic (fever-reducing) medications and other methods to reduce the fever is decided on a case-by-case basis.
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