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Feline Infectious Peritonitis (FIP)
What You Need To Know

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by Arnold Plotnick MS, DVM, ACVIM, ABVP

Introduction

Feline Infectious Peritonitis (FIP) is an uncommon, fatal viral disease of cats. It is caused by infection with feline coronavirus (FCoV). There is much confusion and much misinformation about the disease. I hope the information contained in this article addresses most of the concerns and questions that commonly arise, especially when a veterinarian suggests that your cat may have the disease.

Transmission and Development of FIP

Coronaviruses can affect many different species. They cause intestinal and respiratory disease in dogs and pigs, and are a cause of the common cold in humans. Feline coronaviruses are related to these other coronaviruses. The most common form or “biotype” of FCoV is the enteric (intestinal) form of the virus. This form is easily transmitted between cats. Cats become infected by the fecal-oral route. In other words, FCoV is shed in the feces of one cat, and somehow is ingested by another cat. After the virus is ingested, the virus replicates (i.e. reproduces, making many copies of itself) within the cells that line the intestinal tract. When cats become infected with this form of the virus, they usually show no overt clinical signs. Occasionally, infected cats will get transient, self-limiting diarrhea, probably as a result of the damage to the intestinal cells during viral replication.

Most cats, when they become infected, will shed the virus in their feces for a period of time, usually a few months, and then stop. Infected cats produce antibodies to the virus in response to the infection. Cats may become re-infected with FCoV in the future, and begin shedding again, if they encounter more virus. Again, most encounters are via the fecal-oral route.

Although most infected cats shed the virus for a few months and then stop, a few become persistent shedders, releasing the virus in their feces continuously.

Coronaviruses have an important characteristic: they are fairly prone to genetic change, and seemingly harmless coronaviruses can mutate into a variant virus that may be more pathogenic than the original virus. This, in fact, is how clinical cases of FIP are thought to arise. The relatively benign intestinal coronavirus mutates into a new form type of coronavirus, one that can leave the intestinal tract and cause problems in many different organ systems. This mutated coronavirus is now the deadly, evil FIP virus.

The FIP virus triggers an immune response by the body. The immune response, however, is ineffective and actually makes things worse. Antibodies produced against the FIP virus do not neutralize the virus. The antibodies bind the virus, and these antibody-virus complexes circulate in the bloodstream eventually settling down and accumulating in the walls of the blood vessels where they trigger an intense and harmful inflammatory reaction. These inflammatory lesions can occur in virtually any body system, accounting for the wide range of clinical signs seen in FIP. Normally, when an antibody binds a virus, an immune system cell called a macrophage will gobble up the antibody-bound virus and destroy it. Macrophages, however, don’t destroy the FIP virus, however. Instead, they gobble up the virus and then transport it to other parts of the body, disseminating the disease throughout the body.

Which cats are affected?

Most cases of FIP occur in young cats. In fact, many cases probably occur right after their first infection. This likely has to do with the fact that coronaviruses are prone to mutation. Mutations are more likely to occur when viruses are reproducing themselves, and the highest amount of viral replication occurs right after infection, increasing the risk of the benign intestinal coronavirus transforming into the evil FIP coronavirus. Other stressful factors are often present in young cats, such as an immature immune system, recent re-homing, neutering, vaccination, and perhaps concurrent illness. The peak age for development of FIP is between 6 months and 2 years. Although youngsters fall victim most often, cases are also seen in older cats.

Infection with FCoV is common in cat populations everywhere. Approximately 25 to 40% of household cats are infected with FCoV. In breeding catteries and other large colonies, the number rises to 80 – 100%. Despite this high level of exposure to the virus, FIP is a relatively uncommon disorder. This is because most infections, as stated above, are with the fairly harmless strain of FCoV – the one that produces only mild diarrhea. Cats from breeding catteries and other large multicat households show a higher prevalence of FIP, and this is a reflection of the fact that exposure to FCoV is hard to avoid. In a multicat environment, there may be a few cats who are carriers that continually shed the virus in their feces, reinfecting other cats in the household who also shed the virus, even if only intermittently. In fact, studies have suggested that as few as six cats sharing the same environment are enough to maintain persistent FCoV infections. So, in a multicat environment, the more cats that are chronically shedding FCoV, and the more cats that become reinfected, the higher the risk of FIP developing. Other factors are probably involved, such as genetic susceptibility. A study of all cats diagnosed with FIP over a 16 year period at North Carolina State University revealed that purebred cats were significantly more likely to be diagnosed with FIP, and that Abyssinians, Bengals, Birmans, Himalayans, Ragdolls, and Rexes have a significantly higher risk, whereas Burmese, Exotic Shorthairs, Manxes, Persians, Russian Blues, do not appear to be at increased risk. In colony situations, the incidence of FIP is typically 5%, although this number can vary widely between different colonies. It is not uncommon to see FIP develop in several or al of the kittens from an individual litter over a period of time. In households containing one or two mature cats, the incidence of FIP is very low, perhaps only 1 in 5000.

What are the signs?

Clinical signs associated with FCoV infection are mild – a little diarrhea, perhaps a little vomiting, for a few days duration. FIP, however, can present with a wide variety of clinical signs. There are no clinical signs associated with FIP that are unique for this disease. In general, the disease presents itself in one of two major forms: the effusive (“wet”) form, and the non-effusive (“dry”) form.

As stated above, when the immune system produces antibodies against the FIP virus, the antibodies, rather than neutralize the virus, will bind the virus, and then these antibody-virus complexes circulate in the bloodstream eventually settling down and accumulating in the walls of the blood vessels where they trigger an intense and harmful inflammatory reaction. The inflammation of the blood vessels causes protein-rich fluid to leak through the walls of the blood vessels and accumulate in body cavities. This accumulated fluid is called an effusion, and is the hallmark of effusive or “wet” FIP. On the other hand, the FIP virus can induce an inflammatory response that leads to the formation of clusters of inflammatory cells (called granulomas) accumulating in a variety of organs and structures. The most common sites for granulomas to develop are the abdominal organs such as the liver, kidneys, intestines, and lymph nodes, as well as the eye and the nervous system. The clinical signs that develop depend on which organ or body system is affected. Effusions are not seen in this form of FIP, hence the name non-effusive, or “dry” FIP. “Wet” FIP is more common than “dry” FIP, and probably accounts for 60 – 70% of FIP cases.

Early in the course of the disease, the clinical signs of both wet and dry FIP tend to be non-specific and include fever, lethargy, poor appetite, and weight loss. The vague nature of these signs is what makes FIP so difficult to diagnose early in the course of disease. As the disease progresses, other clinical signs may become more apparent, perhaps allowing the disease to be categorized as the effusive (wet) or non-effusive (dry) form.

Accumulation of fluid in the abdomen, often causing dramatic abdominal distension, is an obvious manifestation of wet FIP, and is the most common place that fluid tends to accumulate. Less commonly, the fluid will be present in the chest, causing breathing difficulty. Now and then, fluid will be present in both cavities. Occasionally, fluid will accumulate in the pericardial sac (the membrane that surrounds the heart), causing cardiac dysfunction. In many cats with the wet form of the disease, the eyes and the central nervous system will be affected. The liver is commonly affected, sometimes causing jaundice.

Clinical signs of the dry form of the disease can be very vague, making diagnosis a real challenge. Persistent fever that doesn’t respond to antibiotics, progressive weight loss, and lethargy tend to be the main signs. As the disease progresses and granulomas develop, other clinical signs will develop depending on the organ that is affected and the degree of involvement. The FIP virus has a predilection for the eyes and central nervous system and signs of neurologic dysfunction (uncoordinated walking) or eye inflammation are not uncommon.

How is it diagnosed?

FIP is one of the most difficult feline disorders to diagnose. The vague clinical signs early in the course of the disease are seen in many other feline illnesses as well. There are no routine laboratory tests that can definitively confirm one’s suspicions of an FIP diagnosis. Instead, one must evaluate the historical results, clinical signs, physical exam findings and laboratory tests. At this point, one may conclude that they have enough evidence for a presumptive diagnosis of FIP. In cases where the diagnosis remains in doubt, tissue biopsies may ultimately be necessary to make a certain diagnosis.

Historically, cases of FIP are more common in young cats (less than 2 years), purebred cats, and cats from multicat environments.

Routine laboratory tests won’t prove or disprove the diagnosis, but may offer evidence to support or refute one’s suspicions of FIP as the cause of the clinical signs. A complete blood count often shows a low lymphocyte count and high neutrophil count. These are very non-specific changes and are seen in many other illnesses.

A serum biochemistry panel also tends to show non-specific changes, however, elevated globulins are a common and important finding, seen in 50 to 80% of FIP cases. . Hyperproteinemia is usually present, the elevation being due to increase in globulins. Albumin levels may be normal, although frequently they are low or low-normal. Because the liver is an organ that is frequently affected in cases of FIP, elevated liver enzymes and high bilirubin levels are not uncommon.

Coronavirus serology – measuring the level of antibodies against coronavirus in the bloodstream – is common and very misunderstood test. A positive test result simply confirms that the cat has been exposed to a strain of FCoV. Excessive reliance should not be placed on this test. It holds no more value than results of routine hematology and serum biochemistry. Keeping I mind that 25 to 40% of the general cat population and 80 – 100% of cats in multicat households are seropositive for coronavirus, a positive result must be interpreted cautiously. As a general rule, cats with FIP tend to have higher FCoV antibody titers, but there is much overlap in titers between healthy cats that were simply exposed to FCoV vs. sick cats currently suffering from FIP. Again, excessive reliance should not be placed on this test. In fact, there have been cases of FIP in which the coronavirus antibody test showed a lack of detectable antibodies. To summarize: low or medium levels of coronavirus antibodies have no diagnostic value because the virus is so ubiquitous. Negative levels suggest a cat is unlikely to have FIP (although about 10% of cats with FIP will have no detectable antibody); and very high levels of antibody offers support for a diagnosis of FIP, but a strongly positive test is not, in and of itself, diagnostic for the disease.

A valuable diagnostic test is the evaluation of effusions in cases of wet FIP. These effusions tend to be “straw-colored” in appearance and is thick, with a sticky feel to it. The protein content is high, with globulins making up more than 50% of the proteins. There are few diseases that produce effusions with such characteristics. Taken with other supportive evidence, an effusion of this type can provide strong evidence for a presumptive diagnosis, especially if this type of effusion is found in more than one body cavity. Detection of coronavirus particles within the cells that are found in the FIP-induced effusions offers very strong support for a diagnosis (in one study, a positive test was 100% predictive for FIP), but this type of test tends to be performed in research laboratories and most commercial laboratories do not offer this test.

Polymerase chain reaction (PCR) has become a popular high-tech method for detecting the presence of infectious organisms. It does this by detecting minute quantities of viral or bacterial DNA and amplifying it to millions or billions of copies so that it can be detected by a routine laboratory method. Like every other test in veterinary medicine, PCR has its pitfalls, and when it comes to FIP, the PCR suffers from the same limitations as antibody testing – it is unable to distinguish which strain of FCoV to which the cat has been exposed. Those PCRs which claim to have detected the mutation which differentiates the harmless intestinal FCoV from the virulent FIP coronavirus have never been validated by the scientific community.

If significant doubts remain concerning the diagnosis of FIP, a truly definitive diagnosis can be achieved through biopsy of appropriate organs. Biopsy specimens may be obtained via exploratory surgery, or by percutaneous needle biopsy, using ultrasound guidance if necessary. When examined under a microscope by a pathologist, affected tissue samples demonstrate pyogranulomatous inflammation, a characteristic type of inflammation seen in cases of FIP. If there is still doubt as to whether FIP is the cause of the inflammation, additional confirmation can be pursued through immunohistochemistry – using special tissue staining procedures – to detect the presence of FCoV within the biopsy specimen.

Is there any treatment?

FIP is progressive and fatal. Cats with FIP tend to succumb to the disease rather quickly, in a few days or weeks. Wet FIP tends to progress faster than dry FIP. Treatment is generally symptomatic and supportive. Nutritional support, antibiotics, and corticosteroids may produce a temporary alleviation of clinical signs, but the disease invariably progresses. In 2004, a report was published that described the use of recombinant feline interferon and glucocorticoids for the treatment of FIP. Twelve cats with FIP underwent therapy. Four cats succumbed quickly; four cats showed a partial remission (surviving for two to five months), and four cats showed a complete remission (survival time greater than 2 years). The four cats that showed long term survival were older cats – between the age of 6 and 16 – and all had the wet form of the disease. Although the number of cats in the study was small, the results were encouraging in that they suggest an apparent therapeutic effect of recombinant feline interferon in select cases of FIP. However, the high cost associated with feline interferon, and the fact that it is only available in Japan, the UK, and the EC countries may be an obstacle for treatment. Ultimately, nearly all cats diagnosed with FIP are euthanized to alleviate suffering. In terms of contagion, the fact that there have been reports of FIP outbreaks in individual colonies of cats suggests that direct transmission of the FIP-causing coronavirus is occasionally possible, however, the FIP virus does not appear to be commonly transmitted in nature and usually dies out when the affected cat dies from the disease.

Prevention and Control

Because the virus causing FIP is an uncommon mutation of a widespread virus, it can be difficult to prevent and control. The most effective management strategies center around preventing and controlling the prevalence of the underlying infection with FCoV. To prevent FIP in household pets, one should avoid obtaining cats from a source where many cats are housed, and try to obtain them from a place where cats or kittens are kept in small stable groups. To put it more simply, one should obtain healthy kittens/cats from a healthy background. One should avoid having large numbers of cats sharing one living space. Household cats kept singly or in small groups are unlikely to develop FIP.

In breeding catteries, one can attempt to control FIP by reducing the incidence of FCoV infection, or one can try to completely eradicate FCoV within the colony. Eradication of infection, however, is very time consuming and laborious. Maintaining a FCoV-free colony can be quite a challenge, given the ubiquitous nature of FCoV infections. A more realistic approach is to consider eliminating FCoV infection in kittens born into the environment where FCoV is present. If a pregnant queen is isolated from other cats one to two weeks before giving birth, and is then kept isolated with her kittens while practicing good hygiene procedures to prevent environmental spread of infection to the kittens), most of these kittens will remain free of infection. Testing kittens for FCoV antibodies before they are weaned will yield invalid results because kittens derive their antibodies from their mothers, and a positive result merely confirms that the mother was exposed to FCoV. After weaning, however, the queen can be removed and the kittens still kept isolated and tested at 12 – 16 weeks of age for antibodies to FCoV. If the litter tests negative, the isolation procedure has been successful. These kittens are FCoV negative and would theoretically be incapable of developing FIP since they do not have the coronavirus in their body. The isolation procedure sometimes fails if the queen herself is shedding FCoV in her stool and passes it to the kittens. This might be avoided if the kittens are weaned early (at 5 to 6 weeks of age), because the antibodies against FCoV that the kittens obtain from the mother may prevent the kittens of acquiring the infection. Raising FCoV-free kittens requires considerable commitment from breeders.

Good hygiene is always important when trying to minimize the prevalence of FIP. Bearing in mind that the fecal-oral route is thought to be the major way in which the virus is spread, some practical control measures that have been suggested include having enough litter boxes (ideally, one for every two cats), keeping litter boxes away from places where food and water are kept, and keeping all litter boxes very clean. Feces should be removed at least once daily, and litter should be changed as often as practical. Cats should be kept in small stable groups. Regular brushing of the hair coat (especially longhaired cats) is recommended to remove any feces or litter that might get stuck in the fur.

A commercial FIP vaccine is available, however the use of the vaccine is controversial. The vaccine is administered intranasally (i.e.drops in the nose). Different studies of the vaccine have yielded very different results, and the efficacy of the vaccine remains questionable. The American Association of Feline Practitioners and the Academy of Feline Medicine, in their regularly published guidelines for feline vaccination, currently do not endorse the routine use of the FIP vaccine at this time.

       

Updated 3/28/06