Diagnosis of FIP: Facing the challenge

Feline infectious peritonitis (FIP) is a disease process initiated in some cats by the effects of a corona virus (FCoV). Clinical signs may include fever that is not resolved by antibiotic therapy, anorexia and weight loss.

Figure 1: Mixed cerebrospinal fluid cell population in a cat with neurologic signs associated with FIP.
In the "effusive form" of FIP, there is a protein rich exudate in the abdominal and/or pleural spaces. The exudate normally contains nucleated cells (often less than 20,000/ul) without bacterial involvement unless secondary infection is a sequellae. The "non-effusive" or "dry" form of FIP may present with ocular involvement, neurologic signs or both. Pyogranulomatous nephritis may occur.

Diagnosis of FIP poses a real challenge to the clinician. Protein-rich exudate may be present with other clinical conditions such as abdominal neoplasia, cholangitis or peritonitis associated with intestinal rupture. Heart failure, pyothorax or Chylothorax with pleural effusion must be ruled out. The working diagnosis of the effusive form based on blood tests, fluid evaluation and virus detection from cells found in the exudate is somewhat more straightforward than in the dry form. However, accurate and confident diagnosis of FIP is still difficult due to the lack of pathognomonic clinical, hematological and biochemical abnormalities. In a recent publication, Hartman and coworkers in Comparison of different tests to diagnose feline infectious peritonitis (J Vet Intern Med 2003; 17:81-790) determined the sensitivity and specificity, as well as positive (PPV) and negative (NPV) predictive values of different clinicopathological variables and virological methods used to support an FIP diagnosis. In this retrospective study, the authors evaluated 1,108 cats, including 488 with histopathologically confirmed FIP and 620 representative controls. The most consistent clinicopathologic finding in cats with FIP was an increase in total serum protein concentration (mainly, globulins) with a decrease in the albumin to globulin ratio, a finding in about 50 percent of the cats with effusion and 70 percent of cats without effusion. A value of 0.8 (or lower) for the serum albumin to globulin ratio strongly supports a diagnosis of FIP. Serum total protein concentration was not found to be a good indicator of FIP. Elevated total serum protein concentration may be seen with chronic antigen stimulation as with calici virus infection, upper respiratory disease or multiple myeloma. In the FIP effusions, the albumin to globulin ratio and the total globulin level tend to be higher than in serum (respective cutoff values of 0.9 and 1.0 g/dl support FIP diagnosis). FIP antibody titers (or better said¬Ö antibodies to a large group of closely related corona viruses) must be interpreted with caution. High antibody titers are frequently found in asymptomatic cats, and most of those cats will never develop clinical FIP. In addition, antibody titers may decrease terminally in cats with fulminant FIP, or be non-detectable because they are bound in antigen-antibody complexes.

In this study, the highest antibody titers (1:1600) had the greatest diagnostic utility when compared to total protein, globulin, albumin to globulin ratio, the presence of antibodies (any titer), antigen antibody complex detection or serum polymerase chain reaction (PCR). However, only 36 of the 488 histopathologically confirmed FIP cases developed titers of 1/1600 with the assay employed in this study.

FIP may be associated with meningo-ependymitis. Inflammatory cerebrospinal fluid (CSF) is characterized by an increased protein concentration and white blood cell pleocytosis with a mixed white blood cell population (Figure 1, p. 1S). In the study by Hartman and co-workers, detection of anti FCoV antibodies (any titer) in effusion had a high PPV (0.90) and a high NPV (0.79). Although not mentioned specifically by Hartman and coworkers, detection of anti FCoV antibodies in CSF associated with a pyogranulomatous cytologic response should be considered for support of FIP as a cause of neurologic signs in a feline.

The authors note that PCR evidence of FCoV in the serum may occur in viremic cats who do not develop clinical FIP, and that technical issues may also yield negative PCR results in some patients who have histopathologically confirmed FIP.

Positive predictive value of FCoV antigen in macrophages from the effusion with immunofluorescent staining reached 1.00. There were no false-positive results in this study. Unfortunately, the negative predictive value was not very high (0.57). Thus, if macrophages in an effusion test positive by immunofluorescence for intracellular FCoV antigen this is very strong evidence supporting a diagnosis of FIP. Conversely, a negative result certainly does not rule out FIP.

Viral protein expressionIn the past, expression of a viral protein, the 7b protein, was postulated to occur only with virulent FCoV, and thus some authors have held that cats with antibodies to this protein were likely to have FIP. A presentation by Kennedy (Kennedy MA. Diagnostic methods for feline viral pathogens. Proc. 21st ACVIM Forum, Charlotte, NC, 2003, 733-735) stated that while cats with FIP are consistently antibody positive for this protein, it may also be present in healthy cats.

In conclusion, the first diagnostic step should be to look for effusion. Diagnostic and cytologic tests that can be performed in effusion have higher predictive values than tests that can be performed in blood. In the absence of effusion, the other serum markers we have discussed in this article may be used to determine which patients are candidates for minimally invasive or invasive procedures to obtain tissue for the "gold standard" of FIP diagnostic support, specifically¬Ö histopathology results.