Diagnosisof FIP

The diagnosis of FIP is based on consideration of the cat’s age, origin, clinical signs and physical examination. Cats 4–36 months of age from high-density environments that manifest a persistent but undulating antibiotic unresponsive fever are immediate suspects for FIP. Very few infectious diseases other than FIP have this signalment. More specific signs of FIP are abdominal distension with ascites, dyspnea with pleural effusion, jaundice, hyperbilirubinuria, distinctive masses on the kidneys and/or mesenteric lymph nodes, uveitis and a range of neurological signs associated with brain and/or spinal cord involvement are all common in cats with either the effusive (‘wet’) or non-effusive (‘dry’) form of FIP (Pedersen, 2014).




Blood work

Common abnormalities usually include a chronic non-regenerative anemia (anemia of chronic disease), leukocytosis with an absolute increase in neutrophils and an absolute decrease in lymphocytes, elevated serum protein associated with high globulin and low albumin, and a low A:G ratio.
Hyperbilirubinemia and hyperbilirubinuria are common in cats with FIP, especially those with the effusive form.
Elevations in serum and urine bilirubin are usually not associated with elevations in liver enzymes (Addie et al., 2009) and the liver is often spared in cats with FIP, evidence of cholestasis is not observed.
Therefore, elevations in blood and urine bilirubin are not due to liver disease, as has been previously suggested, but rather are due to the increased destruction of RBCs in both lesions and in the circulation and difficulties in clearing hemoglobin breakdown products (Pedersen, 2014b).



Analysis of effusion

FIP effusions are clear to moderately cloudy, viscous (egg-white consistency, often with threading) and high in protein (near serum level or higher).
They often form partial clots when placed in a serum tube.
FIP fluids are frequently modified transudates, based on their perceived lack of cellularity.
However, they are inflammatory exudates in the purest sense and do not meet the established physical or physiologic criteria for a modified transudate (Zoia et al., 2009).
Most FIP effusions contain a fair number of cells (500–5000/μL), including macrophages, neutrophils and a low pro- portion of lymphocytes.
FIP effusions are usually not outwardly hemorrhagic in appearance, with the exception of some pleural effusions (Pedersen, 2014b).



Albumin:globulin ratio and serum protein electrophoresis

The A:G ratio is considered a useful predictor of FIP infection. However, the presence of other historic, clinical signs or laboratory abnormalities associated with the disease must be taken into consideration. In a study of FIP cases seen in a referral practice, it was concluded that, when the prevalence of FIP is low, a high A:G ratio is useful to rule out FIP, but a low A:G ratio is not helpful in making a positive diagnosis of FIP (Jeffery et al., 2012). Elevated total protein and/or globulin are often seen in chemistry panels from cats with FIP. In the absence of other common laboratory abnormalities, it is sometimes helpful to analyse these proteins by gel electrophoresis to determine the exact cause of the elevation. In one study, out of 155 cases, 136 (87.7%) cats had abnormal serum electrophoresis profiles, most commonly from a polyclonal increase in gamma globulins. The most common disease classification associated with serum protein abnormalities was infectious/inflammatory disease (80/136; 58.8%), including 39 cats diagnosed with FIP. Monoclonal gammopathy was observed in four cats, including one with FIP, one with lymphoma and two cases of splenic plasmacytoma (Taylor et al., 2010).



Alfa1-Acid glycoprotein (AGP)

AGP was found almost a decade ago to be hyposialylated in cats with FIP, but not in normal cats or in cats with other pathologies (Ceciliani et al., 2004). This study confirmed that serum AGP is a powerful discriminating marker for FIP, but only when coupled with other high-risk factors (Paltrinieri et al., 2007). A Bayesian approach demonstrated that, when the pretest probability of FIP was high based on history and clinical signs, moderate serum AGP levels (1.5–2 μg/mL) could discriminate cats with FIP from others. However, only high serum AGP levels (>3 μg/mL) were highly suggestive of FIP in cats with a low pre-test probability of disease (Paltrinieri et al., 2007). In one study, the specificity and sensitivity of several tests in 12 cats, four of which were confirmed not to have FIP by histopathology and immunohistochemistry, and eight cats with FIP confirmed by histopathology and immunohistochemistry. Results from serum protein electrophoresis, analysis of effusions, anti-feline coronavirus serology, serum AGP concentrations and histopathology were then compared with the confirmed diagnosis. No concordance was found for serology and analysis of effusions, poor concordance was noted for histopathology, fair concordance for serum electrophoresis and perfect concordance for AGP. The conclusion was that immunohistochemistry must always be performed to confirm FIP and, if this is not possible and histopathology is not definitive, elevated AGP concentrations might support the diagnosis of FIP (Giori et al. 2011).



Rivalta test

The Rivalta test has been long used for diagnosing FIP-associated exudates (Hartmann et al., 2003). The test involves placing a few drops of ascites or thoracic fluid into a tube containing a weak acetic acid solution. The appearance of a white flocculent material is seen in a positive test. A positive Rivalta test was once believed to be highly specific for FIP fluid. In a study of 497 cats with effusions, 35% of which had confirmed FIP, the Rivalta test had a sensitivity of 91% and a specificity of 66%, with a positive predictive value of 58% and a negative predictive value of 93% (Fischer et al., 2012). As would be expected, these values increased when cats with lymphosarcoma or bacterial infections were excluded, or when only cats of ≥2 years of age were considered. The Rivalta test appears to be reproducible in samples stored for 21 days at room, refrigerator or freezer temperatures, and with some modifications of acid concentration (Fischer et al., 2013).



Diagnostic Imaging

Ultrasonography and radiology can be very helpful in identifying the presence of fluid, but these are not FIP-specific tests. Ultrasonography or radiology can identify or confirm pleural or peritoneal effusions and assist in sample collection.
Radiology is of more limited value with abdominal effusions but might be more sensitive in detecting small amounts of pleural fluid (Pedersen, 2014b).
Ultrasonography was reviewed retrospectively in 16 cats that had a reasonably confirmed diagnosis of effusive or non-effusive FIP (Lewis et al.,2010).
The liver was judged to be normal in echogenicity in 11 (69%) cats, diffusely hypoechoic in three cats, focally hyperechoic in one cat and focally hypoechoic in another. Five cats had a hypoechoic subcapsular rim in one or both kidneys.
Free fluid was present in the peritoneal cavity in seven cats and in the retroperitoneal space in one cat.
Abdominal lymphadenopathy was noted in nine cats. The spleen had normal echogenicity in 14 cats and was hypoechoic in two.
One cat had bilateral orchitis, with loss of normal testicular architecture.
The authors concluded that, while none of these ultrasonographic findings were specific for FIP, such findings when considered along with appropriate clinical signs should raise the level of suspicion for FIP.

     

Right lateral radiograph of a cat with abdominal effusion caused by FIP infection.


Dorsoventral thoracic radiograph of a cat with pleural effusion secondary to feline infectious peritonitis (FIP).


Abdominal ultrasound of a cat with FIP. A kidney with hypoechoic subcapsular echogenicity is present. The hyperechoic line in the renal medulla is also seen, also known as the renal medullary rim sign.



Feline coronavirus antibody titers

FECVs and FIPVs are virtually identical to each other and evoke the same antibody responses. Titers also tend to be high among healthy cats in the same environments that foster FIP. In one study, many healthy FECV exposed cats had titers by indirect immunofluorescence assay from 1:100 to 1:400 (Pedersen et al., 2008), as had many cats with FIP. However, fewer healthy cats had titers of 1:1600, while titers ≥1:3200 were highly suggestive of FIP (Hartmann et al., 2003). Healthy cats with titers <1:100 infrequently shed FECV in their faeces, while cats with titers of 1:400 are usually positive for feline coronavirus in the faeces (Pedersen et al., 2008).



PCR-based tests

Tests based on PCR have been used to help diagnose FIP for almost two decades (Li and Scott, 1994). Nested PCR is a method that greatly increases the ability of the test to detect very small amounts of feline coronavirus RNA as cDNA (Gamble et al., 1997). Nested PCR involves amplifying a larger fragment of the viral cDNA in the first step, purifying this PCR product and then amplifying a smaller piece from within the larger amplified DNA in a second reaction. A nested PCR was reportedly >90% sensitive and specific in detecting FIPV in ascites from cats with effusive FIP (Gamble et al., 1997). Although very sensitive, nested PCRs are plagued by DNA contamination with PCR products, which causes false positive reactions. The problem of laboratory contamination with PCR products can be avoided by using real time RT-PCR. It is generally conceded that real time RT-PCR is quite sensitive and specific in detecting and semi-quantitating fecal coronavirus (FECV) shedding in both experimental and naturally infected cats (Pedersen et al., 2008, 2009, 2012; Kipar et al., 2010; Vogel et al., 2010; An et al., 2011; Addie et al., 2012; Amer et al., 2012; Wang et al., 2013).

Read more about PCR tests

Immunostaining methods

Although immunohistochemistry is considered to be accurate for the definitive diagnosis of FIP (Giori et al., 2011), there are cases of FIP that test negative depending on the quality of the tissues, the presence of adequate lesions within the material examined, and the quality of reagents and test performance (Pedersen et al., 2014b). Immunohistochemistry of effusions or fluids from cats suspected of having FIP should be used much more often than at present. Effusions often contain numerous virus positive macrophages that can be concentrated onto slides. This technique has also been used successfully to detect FIPV infected macrophages within the cerebrospinal fluid of a cat with neurologic disease (Ives et al., 2013).

Hope for the Future!

We hope new studies will give hope for FIP in cats