Feline Infectious Peritonitis
Matthew Kornya, DVM, ABVP (Feline) Residency Trained, ACVIM (SAIM) Resident, Ontario Veterinary
College, The Cat Clinic, Ontario, Canada
INFECTIOUS DISEASE | NOVEMBER/DECEMBER 2020 | PEER REVIEWED
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FIP is a global disease that traditionally a ects kittens; however, with the
proper combination of exposure, genetic predisposition, and random
mutational events, FIP can a ect any cat of any age. The mortality rate of
FIP has been defined as ≥95%, but recent advancements in antiviral drug
therapy have created the potential for e ective treatment.1,2
Background & Pathophysiology
FIP is caused by infection with a mutant biotype of feline enteric coronavirus (FECV), which can
lead to various complex clinical signs.3-5 FECV infection rates vary signi cantly across
populations, infection occurs in ≈40% of cats worldwide and 90% to 100% of cats in multicat
households3,6; however, only a small percentage (<10%) of cats develop FIP.
e pathogenesis may be di cult to explain to pet owners. In addition to virus exposure, FIP
development depends on environmental stressors, genetic predisposition, and random viral
mutation. e disease is complex and can be best understood when described as a series of
steps3,4,7:
1. Cats are exposed to FECV, which enters enterocytes using a spike (S) protein gene on the viral
surface. Usually, FECV causes self-limiting gastroenteritis that is often undiagnosed. FECV
may also spread systemically without causing FIP.5
2. In some cats, the S protein gene mutates—the viral 3c gene may also be truncated—causing
tropism to change from enterocytes to macrophages/monocytes; this mutated virus is
referred to as FIP virus (FIPV). e mutated virus replicates within immune cells and is no
longer transmissible through the fecal–oral route.
3. In some cats, a strong cell-mediated immune response can control infection, resulting in viral
clearance without clinical disease. If a humoral response predominates, antibodies are
ine ective at controlling infection and can lead to immune complex formation, resulting in
vasculitis and e usion (ie, wet FIP). In the case of a partial cell-mediated immune response,
immune cells are recruited to the site of replication, leading to granuloma formation (ie, dry
FIP). e distinction of wet versus dry FIP depends on the ratio of cell-mediated ( 1) and
humoral ( 2) responses.8
4. Both wet and dry forms result in death if left untreated.
A genetic predisposition to FIP,9,10 wherein decreased gene heterozygosity may contribute to an
altered immune response to FIPV, is likely to occur.2 is may explain the apparent
predisposition of purebred cats to development of disease.9
History & Clinical Signs
FIP typically a ects cats <3 years of age, with a second smaller peak in prevalence in geriatric
cats6; however, cats of any age can be a ected.
Dry FIP can manifest with organ dysfunction, uveitis, neurologic signs, fever, anemia, and/or
lethargy and is caused by granulomas or immune complex deposition. Cats with wet FIP may
have ascites or pleural e usion in addition to the aforementioned signs (Figure 1). Clinical
presentation can vary from minor to life-threatening and involve almost any organ system.
Many cats with FIP are febrile, but fever can wax and wane. Globulins are classically elevated,
often signi cantly (ie, >7 mg/dL), and albumin is typically normal to low (ie, 2 mg/dL or less).
Mild to moderate anemia (ie, hematocrit, 20%-30%), RBC microcytosis, band neutrophilia, and
lymphopenia are common; hyperbilirubinemia (as a result of hemolysis) and
hyperglobulinemia are also often observed. e albumin:globulin ratio is classically <0.4.5,11,12
Lymphopenia and hyperbilirubinemia are more prevalent in wet FIP.
FIGURE 1 Ultrasound image showing abdominal e usion in a cat with wet FIP.
Anechoic fluid is present between organs, distending the abdomen. FF = free
fluid; L = liver; S = spleen; K = kidney
Diagnosis
Serology for FECV is rarely bene cial,6 as serology cannot distinguish FECV and FIPV
antibodies, and some cats with FIP may test negative on ELISA,5,13 which has poor sensitivity for
immune complexes. Serology is likely only useful on a population level as a screening tool for
coronavirus exposure. No evidence indicates that the viral 7b protein ELISA is superior to other
antibody assays.14
Immunohistochemical detection of coronavirus within lesions is the gold standard for diagnosis
of FIP,5,15 but collection of tissue samples is often impractical because of the need for anesthesia
and surgery. Diagnosis is also possible using cytology from ultrasound-guided aspiration of
enlarged mesenteric lymph nodes.5,16
Wet FIP is often readily diagnosed through sampling of e usion, which is typically straw-colored,
translucent, and slightly more viscous than water. Fluid generally has low cellularity that consists
of mildly degenerate neutrophils and macrophages.
Dry FIP often requires more advanced diagnostics, including tissue aspiration or biopsy. A wide
range of diagnostics have been suggested, including routine serum chemistry pro les, diagnostic
imaging, measurement of acute-phase proteins, PCR, and cytology. In the absence of
immunohistochemistry, combinations of methods are often used to diagnose patients with a
high degree of certainty. Consistent nonspeci c clinical pathologic ndings (Table) should raise
suspicion for FIP.6
TABLE
CLINICAL PATHOLOGICAL FINDINGS IN CATS WITH
FIP*,12
Analyte Packed cell volume
Wet Form Decreased
Dry Form Normal to decreased
Analyte Reticulocytes
Wet Form Normal to decreased
Dry Form Normal to decreased
Analyte Neutrophils
Wet Form Elevated
Dry Form Elevated
Analyte Bilirubin
Wet Form Elevated
Dry Form Normal to elevated
Analyte Albumin
Wet Form Normal to decreased
Dry Form Normal to decreased
Analyte Globulins
Wet Form Elevated
Dry Form Elevated
Analyte Albumin:globulin ratio
Wet Form Decreased (<0.4)
Dry Form Decreased (<0.4)
Analyte Lymphocytes
Wet Form Decreased
Dry Form Normal to Decreased
Analyte Mean corpuscular volume
Wet Form Decreased
Dry Form Decreased
Analyte Acute-phase proteins
Wet Form Elevated
Dry Form Elevated
*Not all changes are seen in every cat, and some cats may show no changes. Changes also depend on
presentation (wet vs dry).
e Rivalta test (Figure 2) is an inexpensive and readily performed in-clinic test with an
extremely high negative predictive value for FIP.5,13 is test is positive in e usions with high
protein content (especially acute-phase proteins) and negative in pure transudates. A positive
Rivalta test is consistent with FIP in kittens but is less speci c in older cats, as septic peritonitis
and neoplasia can result in a positive test; however, these conditions can be ruled out via
cytology.
PCR is a valuable modern tool for FIP diagnosis because it allows direct detection of viral RNA;
some experts question its use in all cases, but most consider it to be a useful tool. Detection of
FECV by PCR in tissue or e usion is consistent with FIP but not de nitive, as non-FIP FECV may
also be present in the tissue of healthy animals; however, failure to detect FECV can indicate that
FIP is unlikely.7 Some speci c S protein gene mutations are associated with FIP, and PCR tests
that target these mutations may have higher speci city17,18 (ie, FIP diagnosis is more likely if the
detected virus has one of these mutations). Although potentially clinically useful, PCR testing is
not comprehensive because novel mutations may be missed.17,19 PCR testing of feces is not
useful because fecal coronavirus is not predictive of systemic spread.
PCR sample choice depends on disease presentation; in cases of wet FIP, e usion should be
tested, and in cases of dry FIP, peripheral blood, CSF, aqueous humor, lymph nodes, and/or
organ aspirates should be tested.16,20 Test results should be interpreted based on the sample
submitted; a positive PCR that identi es speci c S protein gene mutations in abdominal e usion
likely indicates FIP, but a positive FECV result in peripheral blood is less speci c.19,20 It should be
noted that testing is done sequentially. Initially, reverse transcriptase PCR for FECV is
performed. When the result is positive, a second PCR should be run to con rm the FECV is FIPV,
not FECV, biotype.
FIGURE 2 Rivalta test procedure; a quick and inexpensive assay of the
inflammatory protein content of a fluid sample. A test tube is filled with 7 to 8 mL
of distilled water, followed by the addition of one drop of glacial (anhydrous)
acetic acid (A). A drop of e usion is placed on top of the solution (B) and
observed; the drop near the top of the tube (C); the drop partway down the tube
(D). If the drop retains its shape and slowly dri s to the bottom of the tube or
remains suspended, the test is positive. In a negative test, the drop dissolves and
the tube appears clear.
Treatment & Management
Treatment of FIP has traditionally been unrewarding, and management of clinical signs and
supportive care to keep cats comfortable have been the mainstays of therapy. Many clinicians
administer corticosteroids to reduce the in ammatory response and improve quality of life, but
there is no evidence that this extends survival.21
e use of immunomodulatory therapy—including immunostimulants, type 1 interferons (IFNs;
eg, human IFNα, feline IFNω), and other similar drugs22,23 intended to bias toward a 1
21,24
response—has been proposed. Preliminary data on these approaches have been
inconsistent, with some data showing positive e ects and others showing no e ects.22
Coronaviral protease inhibitors and nucleoside analogs (eg, GC376 and GS-441524, respectively)
represent major breakthroughs in therapy.25 ese agents inhibit viral replication and disrupt
FIP progression, prolonging patient survival.26 e e cacy and safety of these drugs has been
con ned to laboratory, clinical, and eld studies, but commercialization of GC376 is underway.
Although not 100% e ective, especially with ocular or CNS involvement, these agents are the
most promising therapies to date.23,25,27 Unfortunately, none are currently commercially
available, but the purchase of research-grade drugs online has been widely reported. e
legality, ethics, and e cacy of buying and selling these drugs are beyond the scope of this
discussion.
Prognosis & Prevention
Prognosis for FIP is traditionally very poor (ie, <5% 1-year survival rate).6 Cats with wet FIP are
reported to survive only for weeks11; cats with dry FIP have a longer survival time, but this form
is also fatal. Newer antiviral therapies may signi cantly improve prognosis, and longer-term
survival is possible.27
Although a vaccine for FIP is available in some regions, its e cacy is poor and it is not generally
recommended. Development of an e ective vaccine has been unsuccessful due to the genetic
variability of the virus and a lack of sterilizing immunity (ie, vaccination does not prevent
infection) and antibody-dependent enhancement (ie, pre-existing antibodies may worsen
disease through immune complex formation).28
FIP is not directly contagious. FECV is directly contagious and is an enveloped virus with poor
environmental survivability; thorough cleaning is needed to disinfect the environment.11
Prevention of coronavirus infection is di cult and can be futile in large groups due to the
ubiquity of the virus and number of clinical carriers.
Although diagnosis and treatment of FIP may seem daunting, recent breakthroughs in treatment
and understanding have shed light on this previously enigmatic disease. Simple (eg, Rivalta) and
more complex (eg, PCR) tests have improved FIP diagnostics, and antiviral drugs show potential
for successful therapy.
REFERENCES
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AUTHOR
Matthew Kornya
DVM, ABVP (Feline) Residency Trained, ACVIM (SAIM) Resident
Ontario Veterinary College, The Cat Clinic, Ontario, Canada
Matthew Kornya, DVM, ABVP (Feline) Residency Trained, ACVIM (SAIM) Resident,
earned his DVM from Ontario Veterinary College, where he is working to complete a
small animal internal medicine residency. Dr. Kornya completed an American Board of
Veterinary Practitioners feline residency in private practice and has worked with the
Winn Feline Foundation, AAFP, and regional and national feline organizations and
conferences. His interests are in feline internal medicine, especially retrovirology and
hematology.
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