The difficulties of diagnosis
The virus responsible for causing FIP is thought to be a mutant strain of the nonpathogenic feline enteric coronavirus.1 Since serum antibody tests are unable to distinguish between pathogenic feline coronavirus and the avirulent feline enteric
coronavirus, diagnosing FIP is often difficult and frustrating. Traditionally, FIP is diagnosed based on a high antibody titer
along with a strong clinical suspicion (i.e. lymphopenia, hyperglobulinemia, anemia). The only definitive diagnosis, however, is based on either immunohistochemical
evaluation of surgical biopsy samples or histologic examination of samples obtained postmortem.
The noneffusive form of FIP can be particularly challenging diagnostically because affected animals lack the typical proteinaceous
effusion and can present with vague clinical signs. A key feature of the noneffusive form is ocular involvement. Typical changes
include iritis (color change), aqueous flare, and retinal changes (occasionally seen as retinal vascular cuffing or pyogranulomas).
Although these changes can be seen with feline immunodeficiency virus infection, feline leukemia virus infection, systemic
mycosis, and toxoplasmosis, noneffusive FIP should also be considered. Noneffusive FIP often causes pyogranulomas on the surfaces
of the kidneys and intestines. If large enough, these nodules can be seen ultrasonographically and during exploratory surgery,
but they can be confused with other diseases, most notably lymphoma. Often, the noneffusive form causes variable neurologic
signs depending on where the pyogranulomatous inflammation localizes.
Thus, while the noneffusive form of FIP poses a particular challenge diagnostically, the presence of ocular or renal lesions
or neurologic signs in addition to risk factors (e.g. cats obtained from catteries, cats that are seropositive for feline coronavirus) should raise the suspicion for FIP and
warrant further diagnostic testing such as a biopsy or polymerase chain reaction (PCR) testing.
Diagnostic help: A new PCR test
PCR tests for FIP were developed to detect virus particles in whole blood based on the assumption that FIP virus spreads via
the bloodstream whereas feline enteric coronavirus remains in the intestinal epithelium.2 Unfortunately, virus particles can still be detected in the blood of healthy cats with feline enteric coronavirus, suggesting
that small numbers of feline enteric coronavirus particles do circulate but are unable to replicate or cause problems outside
of the intestinal tract.3
A new PCR test seems to better differentiate FIP from feline enteric coronavirus infection. It takes advantage of the fact
that the pathogenic feline coronavirus is able to replicate within mononuclear cells within the blood, whereas feline enteric
coronavirus may be able to enter the bloodstream but is not able to replicate outside of the intestinal tract.
Detecting active virus replication. The PCR test detects messenger RNA (mRNA) of the M gene of feline coronavirus. The M gene is a highly conserved viral gene
that is only expressed (i.e. mRNA is produced) during viral replication.2 Detection of actively replicating virus particles in the blood is thought to be specific for FIP.2 Since enteric coronaviruses are incapable of replicating in peripheral blood, no mRNA is produced. FIP virus replicates
in monocytes of peripheral blood and, thus, mRNA is produced, which can be detected by using PCR testing. Whole blood is used,
and a DNA copy of the M gene mRNA is made using a reverse transcriptase, which then undergoes several amplification steps
using primers specific for particular M gene sequences.2 The PCR sample is then analyzed with electrophoresis.
Drawbacks of PCR testing. One major drawback of this test is related to the inherent difficulties of PCR testing. The likelihood of inaccurate results
increases if the test is not performed properly (risk of contamination) or if adequate controls are not used. The use of appropriate
primers are necessary to identify gene segments specific for coronavirus. Other reasons for inaccurate results include the
number of virus strains and the rate of mutation of the viral genes.2 Fortunately, the M gene is highly conserved among the coronaviruses and false negative results are low. The other major
drawback of PCR is the potential consequence (i.e. euthanasia) of a false positive result, so the results of any PCR test should be carefully interpreted in the context of
clinical suspicion and not relied on solely for diagnosis.
New PCR test availability. The PCR test is available from the College of Veterinary Medicine at Auburn University.* Although the new PCR test holds promise
for a more accurate diagnosis of FIP, it has not been widely used clinically to determine its ease of use, cost effectiveness,
and reliability.
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