4 Jul 2023
Figure 1. Typical straw-coloured FIP fluid obtained via thoracocentesis.
Feline coronaviruses (FCoV) include feline enteric coronavirus (FECV), which has affinity for enterocytes; and FIP virus (FIPV), which replicates in monocytes and macrophages (Pedersen, 2009).
This change in cell tropism, where FECV mutates to become FIPV and moves from replicating in enterocytes to monocytes, is known as the internal mutation theory (Pedersen, 2009).
FECV infection is usually subclinical, but can result in mild gastrointestinal signs. In contrast, FIPV causes systemic infection commonly referred to as FIP.
Feline coronavirus infection is very common in cats, with up to 50% of cats in single‑cat households and up to 90% of cats in multi‑cat households being seropositive for FCoV antibodies (Pedersen, 1976; Addie et al, 1995).
Although the majority of cats infected with FCoV remain healthy, up to 12% of cats may develop FIP (Addie et al, 1995).
FIP usually affects young cats – most cases are younger than a year of age, typically from shelters or breeding catteries, with certain breeds being more predisposed; however, breed predispositions may vary geographically (Pedersen, 2009).
It is easy to underestimate how common FIP is, and it varies around the world. Therefore, it is worth thinking about how many cats a year in the UK may be developing this devastating disease.
The prevalence of cats being highly suspected of having FIP varies in the general cat population from 0.02% to 1.42% (Addie and Jarrett, 1992; Riemer et al, 2016), increasing to 5% to 10% in catteries, particularly pedigree breeding households (Pedersen, 1976; Addie and Jarrett, 1992).
The UK is home to between 9 million and 11 million pet cats, of which approximately 12% are pedigree (PDSA, 2020), although this increased to 26% by 2022 (Cats Protection, 2022). Approximately a third of these are likely to be young cats, of which about 10% may develop FIP (Addie et al, 1995).
This suggests up to 30,000 cats develop FIP in the UK each year.
We owe it to those cats to know how best to treat them.
Until recently, FIP was a fatal disease, with median survival time of eight days with effusive FIP (Fischer et al, 2011). This changed in 2019, when Niels Pedersen and his team studied the effect of nucleoside analogues in the treatment of FIP. They showed marked improvement and prolonged survival times (Pedersen et al, 2019; Dickinson et al, 2020; see the section about how to treat cases of FIP).
The effusive (wet) form of FIP is generally believed to develop in cats with poor cell‑mediated immune responses, while the non‑effusive (dry) form develops in cats with partial cell-mediated immunity.
The effusive form of FIP is an immune complex vasculitis characterised by leakage of protein-rich fluid into the pleural space, the peritoneal cavity, the pericardial space, and the subcapsular space of the kidneys.
Vascular permeability factors – including vascular endothelial growth factor produced by infected monocytes and macrophages – may increase the vascular permeability in cats with effusive FIP (Takano et al, 2011).
In the non-effusive form, pyogranulomatous or granulomatous lesions develop in multiple tissues – particularly the eyes, brain, kidneys, omentum, spleen and liver.
Some affected cats have characteristics of both forms of FIP, with non-effusive forms often becoming terminally effusive. With treatment this is something we hope to see a lot less frequently now.
The main differential diagnoses for cats with FIP can be seen in Table 1.
| Table 1. Potential differential diagnoses for FIP | |
|---|---|
| Disease | Comparison and diagnostics to differentiate |
| Pancreatitis | Often cats involved in fights. Abdominal and even pleural effusions have high total proteins. With bacterial infection, cell counts are high, with degenerative neutrophils and intracellular bacteria. Culture can reveal bacterial infection. Abdominal ultrasound and/or measurement of feline pancreatic lipase immunoreactivity can be helpful. |
| Septic abdomen | Usually very sick, may present in shock. Effusions have high cell counts, with degenerative neutrophils and intracellular bacteria (although these may be few). Culture can reveal bacterial infection. |
| Pyothorax | Anorexia, vomiting and weight loss is common. |
| Lymphocytic cholangitis | Usually more chronic. Liver enzyme activities (such as alkaline phosphatase and alanine aminotransferase) are increased; fine-needle aspiration of bile or liver, and/or liver biopsy is diagnostic. |
| Toxoplasmosis | Can involve multiple organs. Diagnosis by high IgM antibodies or rising IgG titres. |
| Mycobacterial infections | Fever, lymphadenopathy, respiratory signs, abdominal masses and uveitis are common. Severe hyperglobulinaemia is less common. Cytology may show acid-fast bacteria in tissue samples. PCR and/or culture can be useful, but diagnosis can be challenging. |
| Congestive heart failure | Heart murmur and/or gallop may be present. Mostly modified transudate. Echocardiography is useful to make diagnosis. |
| Lymphoma | Multiple organ involvement. Cytology can reveal neoplastic cells. |
| Carcinomatosis | Can present as single or bicavitary effusion. Cytology can reveal neoplastic cells, but often challenging diagnosis antemortem. |
Anorexia, weight loss, lethargy and pyrexia are common presenting complaints. Owners may notice icterus, ocular inflammation, abdominal distention, dyspnoea, or CNS abnormalities such as ataxia or seizures.
In cats with effusive disease, abdominal distention is common, and pleural effusion can result in dyspnoea and a restrictive breathing pattern, as well as muffled heart and lung sounds. Male cats sometimes have scrotal swelling.
Masses (pyogranulomas or lymphadenopathy) can occasionally be palpated in the abdomen.
No assay is currently available that can determine whether enteric coronaviruses are associated with diarrhoea in cats. Cats with coronavirus RNA in faeces should be evaluated for other causes of diarrhoea.
The only purpose of measuring coronavirus in the faeces, via PCR, is to screen for cats that are chronically shedding FCoV. This is, however, an expensive process as repeat monthly samples are needed over a longer time period (ideally a minimum of nine months).
The diagnosis of FIP (see flow diagram) can be challenging as routine laboratory testing gives no specific findings. Table 2 summarises available laboratory tests.
| Table 2. Useful diagnostics for FIP | ||
|---|---|---|
| Test | Description | |
| Haematology |
|
|
| Serum biochemistry |
|
|
| Fluid analysis – biochemistry and cytology |
|
|
| Quantitative reverse transcriptase PCR (qRT-PCR) – detects feline coronavirus (FCoV) RNA |
|
Idexx FIP Virus RealPCR test
|
| Immunocytochemistry – detects FCoV antigen on cytology samples |
|
|
| Immunohistochemistry – detects FCoV antigen on histology samples |
|
|
Complete blood cell count (CBC) usually shows mild, non‑regenerative anaemia, microcytosis, neutrophilia (with or without toxic changes), lymphopenia and thrombocytopenia or thrombocytosis.
Serum biochemical findings often include hyperproteinaemia, hyperglobulinaemia, hypoalbuminaemia, increased liver enzyme activities, hyperbilirubinaemia and electrolyte imbalances.
Low albumin:globulin ratio (A:G) can aid in diagnosis of FIP, with A:G 0.4 or lower making FIP likely. In one study, an A:G of 0.5 had a positive predictive value of 89%, while an A:G of 1.0 had a negative predictive value of 91% (Hartmann et al, 2003).
When hyperglobulinaemia is detected, protein electrophoresis usually shows polyclonal gammopathy with greatest increases in the gamma‑globulin fractions (Taylor et al, 2010).
Other diagnostics can be variably helpful in making a diagnosis of FIP. Acute phase proteins – particularly α1-acid glycoprotein (AGP) – is often increased (1,500μg/ml and higher), but it can also be increased with other inflammatory and neoplastic diseases.
Measuring FCoV antibodies in the blood – or effusive fluid of cats with FIP – is not helpful as most cats with FCoV infection will be seropositive regardless of whether they go on to develop FIP, and about 10% of cats with FIP are seronegative.
Ultrasound examination often confirms pleural or peritoneal effusion in case of effusive FIP (Figure 1), and abdominal lymphadenopathy and renal medullary rim sign can be seen in both effusive and non-effusive FIP.
Fluid analysis can be helpful in cases of effusive FIP. The effusions are mostly consistent with modified transudate or exudate, being high in protein (3.5g/dL and higher) and having low cellularity (nucleated cells fewer than 5,000cells/μL). Mixed inflammatory cell populations occur most commonly; non‑toxic neutrophils predominate in most cases, while in some cats, macrophages are the primary cell type.
Measuring protein and AGP concentrations in effusions – and calculation of the A:G ratio – can be very helpful in making the diagnosis of effusive FIP.
The gold standard for diagnosing FIP is immunohistochemistry (IHC), which detects FCoV antigen in macrophages by immunofluorescence or immunoperoxidase methods. Where effusions are present, they can be spun down and the cell pellet processed as for IHC (see Table 2 for lab test availability).
FCoV RNA can also be detected in fluid, tissue aspirates or biopsies by reverse transcriptase PCR (RT-PCR). The specificity and sensitivity of RT-PCR varies based on the test and sample used for diagnostics, with highest specificity being on pleural and peritoneal effusion, as FCoV is unlikely to be in effusions from other causes.
Quantitative RT-PCR (qRT‑PCR) is very useful, as finding a large amount of FCoV in an effusion or cell pellet would not be expected in non‑FIP cases. The IDEXX FIP Virus RealPCR Test detects certain spike mutations, which may be present in approximately 70% of cases, and offers another possibility.
Diagnosis of non-effusive FIP can be even more challenging due to the absence of effusion. Fine-needle aspirates of enlarged kidneys or abdominal lymph nodes can be used to generate a cell suspension that can be used for qRT-PCR, or for IHC after making a cell pellet.
Abdominal lavage with sterile saline may also be useful at generating cell suspension to process to IHC.
Surgical biopsies of lymph nodes and/or other organs can be taken for histopathology and IHC to confirm FIP; however, this is not always possible in an already very sick kitten.
In cases of neurological FIP, CSF can be taken for analysis and qRT-PCR, and specific MRI changes are almost pathognomonic for FIP.
Cats with ocular involvement can undergo aqueocentesis and qRT-PCR performed on aqueous humour.
A summary of useful diagnostics for FIP can be seen in Table 2. The European Advisory Board on Cat Diseases also has guidelines for diagnosis.
In most cases of the non‑effusive (and sometimes the effusive) form, it is possible to get to a presumptive diagnosis of FIP. It is usually based on the combination of clinical and clinicopathological findings, and the exclusion of other causes for the presenting clinical signs.
It is important to consider the high costs of treatment, so it is best not to use all available funds trying to completely confirm an FIP diagnosis. Take the aspirates and submit them, including sending effusions for culture, then start treating pending getting the results.
