At worst, kittens may get mild diarrhea. Many show no clinical signs at all. The immune system makes antibodies against the virus but does not eliminate it, and the virus continues to reside in the intestinal tract usually causing no further problems for the cat.
Occasionally, for reasons not fully understood, the harmless intestinal coronavirus can change or mutate, gaining the ability to leave the intestinal tract and cause horrible problems. The immune system tries to defeat the virus, but the virus manages to evade it. This mutated intestinal coronavirus is now the evil FIP-inducing coronavirus.
The FIP virus causes damage to blood vessels, allowing fluid to leak through the vessel walls. Effusions (collections of fluid) can develop in the abdominal cavity, chest cavity, and pericardium (the sac around the heart) resulting in what is referred to as the “wet” form of FIP. Some cats develop nodular accumulations of inflammatory cells called granulomas throughout many of the body’s organs. This form of the disease is known as the “dry” form of FIP.
Diagnosis of the disease is difficult because clinical signs are vague and non-specific. Most cats are young (usually less than one year), and show lethargy, weight loss, poor appetite, and a fever that doesn’t respond to antibiotics. A serum chemistry panel often only shows elevated protein (mainly in the form of increased globulins) unless the virus has begun to affect the kidneys or liver, in which case the liver and kidney parameters may be abnormal. The wet form is easier to diagnose because the presence of fluid in the abdomen or chest is relatively easy to detect and fluid analysis can give additional information supporting the diagnosis. The dry form remains one of the more challenging diseases for veterinarians to diagnose.
There is no simple blood test for FIP. Many laboratories offer veterinarians an “FIP test”, but these tests only measure antibodies to coronaviruses in general. It cannot distinguish whether the antibodies are there due to the cat being infected with the harmless intestinal version of the coronavirus, or the deadly FIP version of the coronavirus. A positive test does not mean that the cat has FIP. Until a rapid reliable test is developed that allows veterinarians to make a diagnosis, biopsy of the affected organs or tissues remains the only way to definitively diagnose FIP, although Auburn University offers an assay that they claim is very good for diagnosing FIP.
A commercial FIP vaccine is available, however, 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 recommend the FIP vaccine at this time.
FIP is progressive and fatal. Cats with FIP tend to succumb to the disease rather quickly, in a few days or weeks. The “wet” form of 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.
A few years ago an article appeared in the Journal of Feline Medicine and Surgery about a potential new treatment for FIP. This was very exciting for us feline practitioners, because FIP is a truly devastating disease that leaves us totally helpless. In the study, 12 cats with FIP were given prednisolone and recombinant feline interferon. Four of the cats died relatively quickly. Four cats survived for a short period of time – between 2 and 5 months. The last four, however, showed prolonged survival. This was an uncontrolled study, but it was really all that we had.
Not long after the article came out, I diagnosed a cat with FIP. I mentioned the new study to the client, and they were interested. A problem: the interferon that we use in veterinary practice is recombinant human interferon. Recombinant feline interferon is not available in the United States. It’s available in the European Union. Well... I managed to score some; we won’t go into the details. I used it on the cat, but to no avail. The cat (a kitten actually) succumbed to the disease. Not long after that, a controlled study of the use of recombinant feline interferon in over 50 cats with FIP was published. The study concluded that recombinant feline interferon was ineffective in treating FIP. Darn it.
An article was recently published in the November 2009 Journal of Feline Medicine and Surgery on the use of polyprenyl immunostimulant for the treatment of FIP. Polyprenyl Immunostimulant is an investigational veterinary drug. The drug is given orally and it has low toxicity. In the report, three cats with the dry form of FIP were treated with this new drug. Two of the three cats are still on treatment and are alive and well. Once cat was treated for only 4.5 months; that cat survived 14 months, which is pretty long. (He might have survived longer if the owners had continued treatment.)
Once again we have a small, uncontrolled case study. The authors, however, are university professors who are very well known in the veterinary community. Of course, we’ll have to wait for a larger, controlled study before we can make any conclusion regarding whether this is truly is a good treatment option. It’s gratifying to see that there are veterinarians working hard to try to find some type of treatment… any type of treatment… for this terrible disease.
(Thanks to catexpert.blogspot.com and Dr. Arnold Plotinick)
Feline Infectious Peritonitis (FIP)
What You Need To Know
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.