Feline infectious peritonitis (FIP) is a baffling and clinical important disease of cats caused by a virulent biotype of feline coronavirus. Despite the fact that the disease is relatively common, veterinarians are often faced with a diagnostic dilemma because there are no individual tests that are reliable for the diagnosis of FIP and the clinical picture is highly variable.

Biology

Feline coronaviruses are large, enveloped viruses with an RNA genome. There are two biotypes of feline coronavirus (FCoV): feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). The term FCoV encompasses both biotypes. FECV is a very common, highly infectious feline virus. The virus is shed in feces of infected cats, but shedding patterns vary. Infection is by the fecal-oral route. It has been estimated that in multi-cat households where FECV has been introduced, 80–90% of all the cats will be infected. In the general cat population, infection rates may reach 30–40%.

The majority of cats with FECV (about 90% or more) remain healthy. In a small number of cases, FECV infection is the first step in a chain of events leading to FIP. Coronaviruses are RNA viruses with a very large genome prone to mutations. While most replication errors are harmless, some will have the effect of giving the coronavirus the ability to cause disease. The exact mutation responsible for the FIPV biotype is not known, but likely involves various point deletions or mutations.

The most commonly accepted theory is that virulent FIPVs arise via mutation from avirulent forms within an individual cat. The vast majority of cats do not "catch" FIP, but they become affected when their own FECV infection mutates. FECV primarily infects the mature intestinal epithelium and is shed in feces. FIPV primarily infects monocytes and macrophages. FIPV are no longer localized in the intestinal tract and are rarely shed in feces. Transmission of FIP directly from cat to cat is therefore the exception, not the rule. Cats that are ill with FIP are unlikely to be a risk to other cats, especially to adults, and may not need to be isolated.

Clinical Presentation

Most cats affected with FIP are young, particularly between 3 months and 2 years of age. Other risk factors include:

 Source: multi-cat home, shelter, cattery

 Pedigreed breeds: Abyssinian, Bengal, Birman, Himalayan, Ragdoll, Rex; may vary by country

 Genetic susceptibility

 Concurrent diseases, especially feline leukemia virus (FeLV) infection

 Stressors: rehoming, recent elective surgery, inter-cat conflicts, etc.

FIP presents in two clinical forms: effusive (wet) and noneffusive (dry). However, the two forms are not mutually exclusive and may occur in the same patient, although usually as a transition from one form to the other.

Clinical signs depend on the predominant form of the disease and the organ systems affected. Some clinical signs are common to both forms:

 Lethargy

 Anorexia (partial or total)

 Weight loss (often out of proportion to the decrease in appetite)

 Chronic fluctuating fever nonresponsive to antibiotics

 Poor growth rate in kittens

Overt clinical signs may be apparent for a few days to a few months, but in retrospect may have been preceded by a long period of vague ill health and poor growth in kittens. Generally the effusive form progresses more rapidly than the noneffusive form.

Clinical signs associated with the effusive form are due to immune complex damage of small blood vessels (vasculitis) with the resulting leakage of serum protein and fluid into body cavities. The most common clinical feature is ascites. Typically, the abdominal distension is nonpainful and a fluid wave can be palpated. If pleural effusion occurs, the primary clinical signs may include dyspnea, tachypnea, open-mouth breathing, and cyanotic mucous membranes. Heart sounds will be muffled on thoracic auscultation.

Clinical signs associated with the noneffusive form depend on the body system affected and are due to localized perivascular infiltrates of inflammatory cells (pyogranulomas) in the parenchyma of organs. Thoracic or abdominal effusions are either absent or too scant to be appreciated clinically. The most common clinical presentations involve the eyes or CNS. Ocular involvement may manifest as anterior uveitis with hyphema, hypopyon, aqueous flare, miosis, and keratic precipitates. CNS involvement is common and may manifest as seizures, ataxia, nystagmus, tremors, depression, behavior or personality changes, paralysis or paresis, circling, head tilt, peripheral neuropathies, hyperesthesia or urinary incontinence.

Abdominal involvement with FIP may include granulomas in mesenteric lymph nodes, kidneys, or liver, as well as adhesions throughout the omentum and mesentery that may be palpable as masses and visible with ultrasound. Lesions in the gastrointestinal tract may cause diarrhea or sometimes vomiting or obstipation. Focal granulomas may be found in the ileum, ileocecocolic junction, or colon. Involvement of the cecum and colon produces a distinct form of FIP with signs of colitis (soft stools containing blood and mucus).

Diagnosis

No single test or indicator is reliable for the diagnosis of FIP. The diagnosis must be based on a preponderance of evidence gathered from patient signalment, medical history, physical examination and laboratory findings. Tests on effusions have greater diagnostic reliability than tests on blood or serum. Therefore, the first step should be evaluation of the patient for evidence of effusion using radiographs and/or ultrasound if necessary.

The effusion found in FIP is a nonseptic exudate with the following characteristics:

 Straw to golden yellow color, viscous, clear to slightly cloudy, frothy when shaken

 High specific gravity (1.017–1.047)

 High protein (typically > 3.5 g/dl, often 5–12 g/dl)

 Albumin:globulin ratio < 0.45 (ratios of 0.6–0.8 may have a poor positive predictive value)

 Low to moderate cellularity (< 5000 cells/μl)

Other laboratory tests that may be used in the diagnosis of FIP include serum chemistries and the complete blood cell count (CBC). CBC results are variable and nonspecific but may include neutrophilia with a mild left shift, lymphopenia (< 1500/μl), and anemia of chronic disease.

Serum chemistry changes may include:

 Albumin:globulin ratio < 0.45

 Total serum protein > 8.0 g/dl

 Total serum globulins > 5.1 g/dl

 Hypoalbuminemia

 Elevated liver enzymes, hyperbilirubinemia, hyperbilirubinuria

 Azotemia

Results of serum chemistries and CBC may also be normal in cats with FIP.

Changes in acute phase proteins are currently receiving attention as ancillary diagnostic tests for cats with FIP. In particular, alpha 1-acid glycoprotein (AGP) levels > 1500 μg/ml have been suggested as markers for FIP. However, elevations in acute phase proteins are not pathognomonic for FIP and may be associated with a variety of other diseases. Currently, these tests are not widely available from commercial diagnostic laboratories in North America.

Histopathology on tissues (from percutaneous ultrasound-guided biopsy, laparoscopy or laparotomy) remains the gold standard for diagnosis of FIP and is underutilized by practitioners. A coagulation profile should be performed before biopsy, as some cats will have problems with hemostasis due to DIC. Perivascular pyogranulomatous inflammation is the hallmark of FIP. Immunohistochemistry can be used to confirm the presence of macrophages within pyogranulomas and can be performed on formalin fixed and paraffin embedded tissues.

All coronavirus antibody titer tests are nonspecific and cannot be used alone to diagnose FIP. Serum titers often provide information confusing to the clinician. Cats with FIP tend to have higher titers than cats without FIP, but the overlap is considerable. Cats with FIP may have negative coronavirus antibody titers. A positive coronavirus antibody test does not rule in FIP and a negative coronavirus antibody test does not rule out FIP. In fact, when the viral load is high, virus may bind antibody and cause a falsely low or negative antibody test result.

Polymerase chain reaction (PCR) is a sensitive technique for detecting minute amounts of viral RNA in blood and effusions. However, no single unique genetic sequence has been identified as associated with FIP. PCR tests cannot be used as sole diagnostic criteria for FIP, but may be useful as ancillary tests if performed by a reliable laboratory.

Treatment

Polyprenyl immunostimulant (PI) is an investigational veterinary biologic (Sass & Sass, Inc.; Oak Ridge, TN) comprised of a mixture of plant-derived polyisoprenols. Limited information suggests it has low toxicity, is orally absorbed, and may upregulate biosynthesis of mRNA of Th-1 cytokines. In a recent case series, three cats with noneffusive FIP were treated with PI. Two of the cats survived at least two years after diagnosis; the third survived 14 months despite a limited course of treatment. The drug does not seem to be effective for cats with effusive FIP.

Palliative care may be appropriate for some patients, particularly those cats with mild clinical signs, that are not too debilitated and that are still eating. Recombinant feline interferon-omega (Virbagen Omega, Virbac S.A., Carros, France) had shown some initial promise, in a small, uncontrolled clinical trial. However, a larger placebo-controlled double-blind trial found no statistically significant difference in the survival time of cats treated with recombinant feline interferon-omega versus placebo.

References

1.  German A. Update on feline infectious peritonitis. In Practice. 2012;34:282–291.

2.  Giori L, Giordano A, Giudice C, et al. Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases. J Small Anim Pract. 2011;52:152–157.

3.  Pedersen NC. A review of feline infectious peritonitis virus infection: 1963–2008. J Feline Med Surg. 2009;11:225–258.

4.  Tsai HY, Chueh LL, Lin CN, et al. Clinicopathological findings and disease staging of feline infectious peritonitis: 51 cases from 2003 to 2009 in Taiwan. J Feline Med Surg. 2011;13:74–80.