Navigating FIP Diagnostics
Making sense of the complicated test options
Dear Readers,
On this Substack we recently discussed a new variant of Feline Infectious Peritonitis (FIP) that is spreading in Cyprus. FIP is a complex and usually fatal disease that has long posed challenging to diagnose. However, new diagnostic advances have paved the way for more accurate and timely identification. With several new antiviral drugs showing promise in extending survival of cats with FIP, getting the right diagnosis is more important than ever. In this article, we will review the latest recommendations for FIP based on the 2022 American Association of Feline Practitioners (AAFP) diagnostic guidelines.
TL;DR Summary for Free Subscribers:
Accurate FIP diagnosis involves integrating clinical signs, laboratory tests, and imaging, with advanced diagnostics like immunocytochemistry, histopathology, and PCR being critical. Feline coronavirus serology is discouraged due to its inability to distinguish between benign and virulent forms of the virus.
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The full continuing education article including photos, tables, and details on how each test performs continues below…
Basic Diagnostic Testing
FIP is a complex, systemic disease caused by feline coronavirus (FCoV), endogenous viral mutations, and its interaction with the host immune system. It has a biphasic age distribution, with cats <2 and geriatric cats being overrepresented, although cats of any age may develop the disease. Purebred cats appear to be at higher risk than mixed breed cats, and immunosuppression may also be a risk factor. Cats with FIP, particularly the “dry” form (without effusions), can present with a constellation of vague clinical signs, including lethargy, inappetence, weight loss, fever, lymphadenopathy, etc. Likewise, routine clinicopathologic tests like CBC and biochemistry panels may also be non-specific, and simply indicate systemic illness, inflammation, etc (see the table below). This means veterinarians must rely more on advanced diagnostics than with other more straightforward diseases. Furthermore, since the inflammatory pattern in FIP lesions can overlap with other chronic infectious diseases (ie. Mycobacteria, Toxoplasma, etc), it is critical to identify that feline coronavirus is indeed the causative agent.
Advanced Diagnostic Testing
Detection of viral antigen is the gold standard for diagnosis of FIP
Cytology
Cytology can be useful in supporting the possibility of FIP, but there are no pathognomonic findings. FNA cytology results from nodular or mass lesions that occur in cats with both dry and wet form FIP will reveal sterile inflammation that may be neutrophilic (purulent), pyogranulomatous (neutrophil and macrophage predominant), or granulomatous (macrophage predominant), and may have a lymphoplasmacytic component.
Fluids from cats with effusive FIP typically have very high protein concentrations, often >4.0 g/dL. The nucleated cell counts can vary widely from a few hundred per microliter (in the range for a transudate) to exudates with TNCC >20,000/uL. Like FNA of mass lesions, these usually reveal sterile inflammation with a variable WBC differential. These effusions often have a classic pink stippled background representing a fibrinous exudate:
A quick note about Rivalta’s test: This is a simple bedside assay that attempts to differentiate between transudates and exudates by adding acetic acid to the effusion and looking for a precipitate. Some clinicians will use this as a diagnostic test for FIP. However, based on the poor specificity and positive predictive value in most studies, the primary use of this test should be to rule out FIP in cats with a negative result. One study that evaluated Rivalta’s test for FIP found it had a sensitivity of 91.3% and a negative predictive value of 93.4%.2
Histopathology
Histopathology can be performed ante-mortem from biopsy of any lesions, particularly masses/nodules or enlarged or abnormal lymph nodes or organs, or post-mortem during necropsy. In addition to pyogranulomatous inflammation, lesions usually show vasculitis and perivascular necrosis. Ancillary stains like Gram, PAS/GMS and acid-fast to rule out occult bacterial/fungal/protozoal organisms can be very useful. Often, histopathology is combined with IHC to detect viral antigen and confirm FIP (see below).
Antigen Detection
Detection of viral antigen by immunocytochemistry, immunohistochemistry, or immunofluorescence is the gold standard for diagnosis of FIP. Many labs can perform IHC on tissues, but ICC/IF on effusions or cytology slides may also be available. Inquire with your lab about what tests they offer, their protocols, and submission requirements.
PCR
Amplification of FCoV viral nucleic acid by PCR can confirm FIP in a cat with compatible signs and lesions. However, the diagnostic accuracy varies by the specifics of the test and the fluid or tissue sampled. Labs may design primers targeting the Spike (S), Membrane (M), Nucleocapsid (N), or other FCoV genes, and they may or may not sequence for specific mutations associated with FIP. PCR is NOT recommended to be performed on blood because healthy cats without FIP may have low-level viremia that is not associated with development of the disease. See the table below for data on the performance of specific assays by sample type.
Serology
Lastly, we need to talk about the elephant in the room: Serology for feline coronavirus. This is NOT recommended for the reasons below, and some have quipped “More cats have died from coronavirus serology tests than from FIP itself” (due to being euthanized based on “positive” results).
Why is this? Serology only measures an antibody response to feline coronavirus (FCoV) and cannot distinguish between the benign enteric form and the highly virulent FIP form. Due to the ubiquity of the benign enteric feline coronavirus among cat populations, nearly all cats have been exposed to FCoV and can be positive. Vaccination, although uncommon, can also cause seroconversion. As you would expect, this makes the sensitivity and specificity of coronavirus serology in cats quite poor. A positive does not mean the cat has FIP, and a negative does not rule out this disease.
Summary
In summary, the latest recommendations for diagnosing Feline Infectious Peritonitis (FIP) in cats emphasize a multifaceted approach. It requires consideration of the cat’s signalment, history and clinical signs, along with results from laboratory tests (such as cytology/biopsy, detection of viral antigen, and polymerase chain reaction), and imaging (like ultrasound) to provide the most accurate diagnosis. While FIP remains a challenging disease to diagnose definitively, hopefully this information makes sense of the numerous test options and guides you in your future cases.
References & Further Reading:
1. Thayer V, et al. 2022 AAFP/EveryCat Feline Infectious Peritonitis Diagnosis Guidelines. Journal of Feline Medicine and Surgery (2022) 24, 905–933. https://journals.sagepub.com/doi/pdf/10.1177/1098612X221118761
2. Fischer Y, Sauter-Louis C, Hartmann K. Diagnostic accuracy of the Rivalta test for feline infectious peritonitis. Vet Clin Pathol. 2012 Dec;41(4):558-67. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169324/