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FELINE CHRONIC GINGIVOSTOMATITIS (FCGS)Diane D. Addie

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This lecture has 4 sections with 4 key messages:

1. Feline chronic gingivostomatitis (FCGS) is NOT the gingivitis associated with ordinary tooth decay and is NOT juvenile periodontitis. It IS a refractory immune-mediated inflammatory condition involving the gingivae and the palatoglossal folds.

2. The aetiology is complex, the role of feline calicivirus (FCV) uncertain, and, in my view, the role of nutrition is underestimated and all cats with gingivitis should be taken off from cereal-based cat foods, at least until they are healed

3. Many treatments may need to be attempted, but CORTICOSTEROIDS SHOULD BE AVOIDED.

4. Avoid vaccinating cats with FCGS with live FCV vaccines

Oral disease is one of the commonest reasons cats are presented to veterinarians

Periodontal disease is a common oral disease in cats. In the United States, the two most common disorders reported for cats examined at private veterinary practices were dental calculus (24.2% of cats) and gingivitis (13% of cats). Also, it has been reported that 70% of cats in the age range of 20 –27 mo have signs of periodontal disease. (Ingham et al, 2002)

Periodontal disease is a plaque-induced inflammatory disease of the sup-porting tissue of the tooth and includes both gingivitis and periodontitis. If plaque is left undisturbed, gingivitis develops rapidly. Gingivitis is reversible if plaque is removed from the tooth surface. If gingivitis is left untreated, the cat may develop periodontitis. Periodontitis is irreversible and involves the destruction of the periodontal ligament and the alveolar bone. This leads eventually to tooth loss. Periodontal disease in the cat is a debilitating condition and severely affected cats are reluctant to eat or drink. (Ingham et al, 2002)

What feline chronic gingivostomatitis IS NOT

FCGS is NOT ordinary dental disease with tartar and calculusOrdinary dental disease – i.e. calculus - is relatively easily cured by doing a dental: removing decayed and loose teeth, scaling the tartar off the others and giving broad

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spectrum antibiotics pre and post-operatively to prevent bacteraemia and bacterial endocarditis.1

Mild or moderate concurrent dental disease was found in 71% of FCGS cases (Healey et al, 2007) so how does one differentiate ordinary dental disease from FCGS? In the latter, the extent of gingivitis is exaggerated relative to the amount of tartar present, and the palatoglossal folds may be involved. In addition, FCGS cases continue to suffer from inflamed gingivae after the routine dental procedure.

FCGS is NOT juvenile periodontitisJuvenile onset gingivitis-periodontitis appears in cats less than 9 months of age. Initial signs occur just before or at the time of eruption of the adult teeth (Williams and Aller, 1992) and may be noted at time of presentation for vaccination or neutering, as a thin red line along the margin of the gums or as a more severe gingivitis.

Williams and Aller (1992) noticed a breed predilection in Siamese, Maine Coon and domestic shorthair cats.

Less severe cases may spontaneously regress. Addie documented recovery of one Somali kitten on changing the food from cereal-based dry foods to a mixed wet and meat-based dry food (Applaws, MPM products, Cheshire, UK) in a YouTube video (www.youtube.com/watch?v=wxzVKxFywPE&feature=g-upl&context=G2f5a0cbAUAAAAAAADAA). Some cases respond favourably after removal of any retained deciduous teeth and plaque. However, these cases can progress to FCGS.

FCGS is NOT feline juvenile hyperplastic gingivitis    

1 The use of pre and post-dental antibiotics in animals and humans is controversial: the NICE 2008 guidelines are against their use and studies exist purporting to give evidence that supports that position (e.g. Ahmad et al), although many studies restrict their follow up time to a few days and do not check heart valves. The argument against antibiotic use centres on the rise of multi-antibiotic resistant bacteria, ignoring the much larger roles of antibiotics as food additives for faster growth of factory farm animals (Zurek and Ghosh, 2014; Greger 2006) and commonly used herbicides such as glyphosate (Roundup) causing antibiotic resistance: Kurenbach et al (2015) states “Increasingly common chemicals used in agriculture, domestic gardens, and public places can induce a multiple antibiotic resistance phenotype in potential pathogens. .... The combination of high use of both herbicides and antibiotics in proximity to farm animals and important insects, such as honeybees, might also compromise their therapeutic effects....” Thus veterinary use of antibiotics in our pet cats and dogs is a drop in the ocean compared with their mis-use in factory farms and the unnecessary, horrendous and ubiquitous over-use of herbicides. A case study in BMJ, by Lopez et al (2013), angrily titled “A not very NICE case of endocarditis” documented the unfortunate death of a man whose dentists followed the NICE guidelines. In contrast to the NICE guidelines, the guidelines of the American Heart Association and European Society for Cardiology still recommend the use of antibiotic prophylaxis for those considered to be at high risk. (Lopez et al, 2013). It is my opinion that it is our duty to do our best for each and every individual patient and that antibiotic prophylaxis prior to dentistry is justifiable. We can help the antibiotic problem by choosing organic food and boycotting Roundup and other Monsanto products.

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Juvenile hyperplastic gingivitis appears in cats less than 9 months of age, often first appearing at the time of eruption of the adult teeth (Williams and Aller, 1992). Williams and Aller (1992) noticed a breed predilection in Abbysinnians and Persians. These cases require gingivectomy to eliminate the pseudopockets formed by the gingical hyperplasia (Williams and Aller, 1992). Teeth with resorptive lesions will require removal.

What feline chronic gingivostomatitis IS

Feline chronic gingivostomatitis (FCGS or FCGS), also sometimes referred to as lymphocytic plasmacytic gingivitis and/or stomatitis, faucitis or pharyngitis is a painful inflammatory condition of the palatoglossal folds (fauces) with or without involvement of the gingivae.

Stomatitis is where the inflammation extends beyond the mucogingival junction into the oral mucosa and in which, as well as hyperemia, oedema and bleeding, there may also be proliferation of granulation tissue. (Williams & Aller, 1992) Most authors agree that a diagnosis of FCGS usually requires involvement of the palatoglossal folds (sometimes referred to as the fauces). Other areas that can be affected are the palate, pharynx, tongue and lips (Healey et al, 2007). Dental disease is completely absent in 29% of FCGS cases, and only mild to moderate where present. (Healey et al, 2007). The immune response of a cat with FCGS is abnormal, with an imbalance in the inflamed gingivae and palatoglossal folds towards a mixed Th1 and Th2 instead of a predominantly Th1 response (Harley et al, 1999)

Clinical signs, generally caused by the inflammation which induces pain when opening the mouth, are dysphagia, weight loss, loss of grooming behaviour, ptyalism (excessive salivation), pawing at the mouth and halitosis (Dolieslager et al, 2011). In one study some cats suffering from FCGS were extremely fractious, likely due to the pain from which they were suffering: they returned to their “normal” personalities as their lesions healed (Addie, unpublished observation). Thus such cats may first be presented as behaviour problem cases rather than as dental cases.

The prevalence of FCGS in the UK is 0.7% (Healey et al, 2007). Although any age of cat can be affected, Healey et al (2007) noticed two age peaks: between 1 and 4 years of age, and between 10 and 13 years of age. Male and female cats were equally likely to be affected. Although Healey et al (2007) noticed no breed predisposition, Maine Coon cats seem to be predisposed to FCGS (Addie unpublished observation).

Many cats suffering from FCGS are euthanased due to refractoriness to treatment and possibly because of aggressive behaviour due to the extreme pain of their mouths.

The aetiology of FCGS is complex and multifactorial: a brief summary is presented in table 1.

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Does feline calicivirus have to be present to diagnose feline chronic gingivostomatitis?

The short answer to this question is no – FCV does not have to be present to make a diagnosis of FCGS. FCV was present in a great many cats without FCGS (10 – 25% in cats visiting veterinary surgeries and at cat shows (Coutts et al 1994; Porter et al, 2008) and absent in 46% (Belgard et al) and 30% (Harbour 1991) of cats with FCGS.

The question of the role of FCV in the aetiology of FCGS remains: is FCV a causal organism or merely an opportunistic pathogen? Recovery from clinical signs coincided with cessation of FCV excretion (Addie et al, 2003). However, strains of FCV taken from FCGS cases were unable to reproduce the disease in specific pathogen free cats (Knowles et al 1991) thus FCV fails to fulfil Koch’s postulates.

The question remains – is FCV a causal organism or merely an opportunistic pathogen? What is clear is that the presence of FCV in FCGS cases is not to their benefit: Dolieslager et al (2013) stated: “A positive correlation was observed between clinical disease severity and the presence of FCV (p=0.001).” In addition, there are growing numbers of reports of clinical response to recombinant interferon omega therapy (Leal et al, 2013; Mihaljevic 2003; Mihaljevic 2004; Southerden et al, 2007) though it is not clear whether this is due to its anti-viral or anti-inflammatory activity, likely both.

The role of food in the aetiology of FCGS is underestimated

Food is a very important feature in this condition: prior to the recovery of one case, the cat had been changed to Classic Cat Food (Addie et al, 2003). In addition, after dentistry, cats fed on Hills a/d diet gained more weight and had smaller lesions than those fed on a control diet (Theyse et al, 2003). A FCGS-recovered cat can be made to relapse by feeding him on some dry food such as Friskies or Royal Canin, and to recover again when those foods are withheld (Addie, unpublished observation). The possible explanations are:

1. Allergy / intolerance to some component2. Micronutrient deficiency3. Omega 6:3 ratio4. Exposure to toxins

Many of the larger cat food companies uses poor quality, cereal based, protein in their foods (Hodgkins 2007). Most pet food is made by a process called extrusion, which was developed decades ago to make puffed breakfast cereals. (www.petfoodinstitute.org/?page=DryPetFood: www.madehow.com/Volume-2/Pet-Food.html). When I visited a pet food manufacturer in England, I was shocked to learn that almost all pet foods were the same, basic, kibble. I was told that individual brands differed only in a mix that is sprayed onto the kibble at the penultimate stage of manufacture: just before packaging. Thus high end, expensive veterinary brands sat side by side with the cheapest supermarket own brands, a huge difference in price, a small difference in whatever was sprayed on to the same basic, carbohydrate kibble.

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The plant had to shut down, clean out the machines and put in a completely different set of contents for just two brands: Applaws and Almo Nature.

1. Allergy / intolerance to some food componentContact allergy is recognised as a cause of human gingivostomatitis, (Endo & Rees, 2006). Ironically, the culprit is often cinnamon in toothpaste or chewing gum. Most modern cat food is completely unnatural and completely processed: is it not possible that some component is triggering allergic responses in cats?

2. Micronutrient deficiencyThe most famous micronutrient deficiency resulting in gingivitis is surely scurvy of the human, resulting from vitamin C deficiency? However cats, unlike humans and guinea pigs, can make their own vitamin C. They do require a nutritional source of arginine though and arginine is essential for the healthy function of the immune system: cats evolved as obligate carnivores and I believe that although many of the nutritional needs of cats have been discovered, we do not yet know them all sufficiently to be able to fabricate a diet, based on cereals, which meets all of their nutritional needs. In addition, combinations of components can have unforeseen consequences, for example rice is often used in hyposensitive diets, but rice bran decreases taurine, (Stratton-Phelps et al, 2002) another essential amino acid for the cat (and dog), deficiency of which leads to dilated cardiomyopathy, blindness and infertility.

3. Omega 6:3 ratio The imbalance of omega-6 to omega-2 polyunsaturated fatty acids in the modern human diet are widely accepted as a cause of the increase in chronic inflammatory diseases such as arthritis, asthma, and inflammatory bowel disease (Simopolous, 2008). Corbee et al (2012) hypothesized that a cat food with an omega-6 polyunsaturated fatty acid (ω6 PUFA) to ω3 PUFA ratio of 10:1 would reduce inflammation of the FCGS and accelerate soft tissue wound healing of the gingiva after dental extractions, compared to a cat food with a ω6:ω3 PUFA ratio of 40:1. The cats were fed diets with chicken fat and fish oil as sources of fatty acids. In one diet, part of the fish oil was replaced by safflower oil, resulting in two diets with ω6:ω3 PUFA ratios of 10:1 and 40:1. This double-blinded study in two groups of seven cats revealed that dietary fatty acids influence the composition of plasma cholesteryl esters and plasma levels of inflammatory cytokines. The diet with the 10:1 ratio lowered some pro-inflammatory cytokine plasma levels significantly, compared to the diet with the 40:1 ratio. However, feeding diets with dietary ω6:ω3 PUFA ratios of 10:1 and 40:1, given to cats with FCGS for 4 weeks after extraction of all premolars and molars, did not alter the degree of inflammation or wound healing. The reasons for the lack of clinical response, in my view, are that 4 weeks isn’t long enough, and that the ratio wasn’t low enough: for example a ratio of 2.5:1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4:1 with the same amount of omega-3 PUFA had no effect (Simopolous, 2008). Really the ideal is to get to about 1:1.

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4. Exposure to toxinsCats are uniquely sensitive to certain plant based toxins, notably phenols. Cats evolved with a uniquely carnivorous diet and, as a result of lack of exposure to plant-based toxins (phytoalexins), have presumably lost the need to metabolise these toxins via glucuronidation, which is common in most herbivores and omnivores (Shrestha et al, 2011). It is possible that a plant based (or other) toxin irritates the feline oral mucosa. Grains and cereals can be contaminated with mycotoxins. Most mycotoxins are stable under normal food processing conditions, including sterilization temperatures (120°C). Therefore, if the toxins are present in the raw material used for manufacture they will still be present in the kibble. (Hughes et al, 1999) Some manufacturers do screen deliveries of wheat and other grains for mycotoxins prior to using it (Hughes et al, 1999) though it is possible that there exists some unrecognised toxin irritant to oral mucosa.

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Table 1. The multifactorial aetiology of FCGS has not been clearly elucidated and the following have been implicated:

Possible instigator of FCGS

Comments

Feline calicivirus Instigator or passenger? Present in up to 76% of cases.

Cat’s immune response Shift from predominantly Th1 to mixed Th1 and Th2 in lesions

Food Allergic or intolerant response to a food component: this is a recognised cause of human stomatitis Micronutrient deficiency? Omega 3:6 ratio – too much omega 6 in cereal based diets leads to a chronic pro-inflammatory state

Feline leukaemia virus (FeLV)

Belgard et al (2010) found no association. FeLV is immunosuppressive though, so while you need not test a FCGS cat for FeLV, it is wise to check the mouth of a FeLV positive cat for FCGS.

Feline immunodeficiency virus (FIV)

Present in ~5% of the general cat population and the FCGS population too. Belgard et al (2010) found no association. So you need not test a FCGS cat for FIV, but it is wise to check the mouth of a FIV positive cat for FCGS. At least 4 studies in FIV positive cats have shown a life span equal to uninfected cats.

Bartonella henselae The causative organism of cat scratch disease in humans: there are conflicting reports regarding its relevance in FCGS: e.g. Sykes et al (2010) found an association but Belgard et al (2010) found no association.

Tannerella forsythia (and other bacteria)

“Although the number of cats harbouring T. forsythia was low, 80% of samples in which it was present were from cases with the highest clinical disease severity” (Dolieslager et al, 2013).

Feline herpesvirus Ruled out as a cause of FCGS, but steroid treatment or the chronic pain of the mouth in FCGS cats can cause recrudescence of latent FHV in FCGS cases, causing secondary ocular signs, such as serous discharge, conjunctivitis. In all refractory conjunctivitis and nasal discharge cases, I recommend checking the mouth as a source of underlying chronic stress.

Leishmania infantum “Clinical manifestations compatible with feline leishmaniosis include lymph node enlargement, skin and mucocutaneous lesions, ocular lesions, chronic gingivostomatitis, hypergammaglobulinemia, and normocytic normochromic anaemia.”  (Pennisi 2015)

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Diagnosis

Biopsy is the definitive diagnostic technique and helps differentiate FCGS from possibly similar appearing lesions such as squamous cell carcinoma or eosinophilic granuloma. Virus isolation is the method of choice to detect FCV (PCR is less reliable because FCV is an RNA virus, so it is more difficult to design primers and probes which will detect all isolates.) Obtain three negative tests a month apart before declaring the cat FCV free. Cats with FCGS can be unusually fractious (Addie, manuscript in preparation) and clipnosis can help you obtain a sample without recourse to using a sedative (Pozza et al, 2008).

Treating FCGS

See table 2. At the outset of treating FCGS, it is vital to give the client realistic expectations – to explain that there currently is no single cure for this condition and that you may have to attempt many different strategies before a successful outcome is established. Owners are more likely to elect for euthanasia if they perceive the problem to be intractable or to change veterinary surgeons if they have not been warned in advance that you will likely have to try more than one treatment. It is often a good idea to prepare a practice leaflet explaining the procedure.

Full dental extraction, antibiotics and non-steroidal anti-inflammatory drugsThe only treatment to claim a high cure rate (about 80%) remains full dental extraction by a specialised veterinary dentist. However, the risk of iatrogenic damage to the eyes has to be considered (Smith et al, 2003). Non-surgical treatment is aimed at trying to eliminate FCV, if present; shifting the immune response back to type 1 and restoring normal mouth flora (healthy cat’s mouths have predominantly Pasteurella multocida, cats with stomatitis have abnormal flora, including, in cats most severely affected, Tannerella forsythia (Dolieslager et al, 2013), which, along with Treponema. denticola and Porphyromonas gingivalis, form a bacterial consortium, often referred to as the ‘Red Complex’, that is strongly associated with the clinical progression of chronic periodontitis (Dashper et al, 2011)). Rather creepily, identical strains of T. forsythia were isolated from a human and their cat, (Booij-Vrieling et al, 2010) so don’t kiss your cats unless your oral hygiene habits are excellent – we don’t want you infecting the little furries. Antibiotics of choice include cefavexin (Convenia, Pfizer) and clindamycin hydrochloride (Antirobe, Pfizer) although the latter must be used with caution as oesophagitis has been suspected after its use (as with many tablets in the cat) (Beatty et al, 2006).

Key message: DO NOT USE corticosteroids

Corticosteroids give a misleading initial response due to their ability to diminish pain and inflammation and increase appetite. However, the benefits are short-lived and adverse effects are far more serious and may disable the cat from ever being able to recover from FCGS. In his PhD study, Ross Harley found a “bounce back” effect of corticosteroid use: that not only did FCGS return but it came back worse and more

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intractable following corticosteroids. These are some of the problems associated with corticosteroid use:

corticosteroids thin the mucosal epithelium of the mouth, causing gums to be more friable and less able to withstand bacterial onslaught

they decrease both Th1 and Th2 immune response, stopping the cat from ever clearing the FCV infection

corticosteroids have been documented to induce feline infectious peritonitis in cats who were otherwise asymptomatically infected with feline coronavirus

corticosteroid treatment of a dental case led to fatal leishmaniosis (Leiva et al, 2005)

corticosteroids can re-activate dormant toxoplasma infection with fatal consequences

corticosteroid treatment may lead to recrudescence of latent herpesvirus infection, causing conjunctivitis and upper respiratory tract signs

long term use of corticosteroids predisposes to obesity long term use of corticosteroids predisposes to diabetes mellitus

Pain relief is essentialPain relief is essential – use a non-steroidal anti-inflammatory safe for use in the cat such as meloxicam (e.g. Metacam, Boehringer). However, these may be contra-indicated in cases with chronic kidney disease.

Food It is prudent to remove cats with FCGS from most dry foods and to use as natural and varied a wet food source as possible. Foods used successfully by the author include Classic Cat Food (Butchers, UK) (Addie et al, 2003); Wild Kitty Cat Food (www.wildkittycatfood.com, USA), and Applaws (MPM products, UK). However, no controlled study has been performed as yet due to lack of funding. The author has used Applaws and Almo Nature dry foods on a FCGS-recovered cat without inducing inflammation. However, on Applaws alone he developed fur ball problems, and his diet had to be supplemented with Royal Canin senior which contains psyllium for trichobezoar control.

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Table 2. A summary of current treatment options for FCGS:

AVOID CORTICOSTEROIDS!Treatment Dose Comments

Change of dietTake the cat off dried food (other than those based on meat, e.g. Applaws or Almo Nature) and use as natural a diet as possible – cheap and safe, but must be used in association with other features in this table.

SurgeryRemove all the teeth (usually leave the canines)

Reported to cure 80-90% of cases, but at risk of iatrogenic damage to the eyes. Roots must be removed completely.

Painkillers / Non-steroidal anti-inflammatory drugsMeloxicam (Metacam, Boehringer)

Day 1: 0.3mg/kg sid with food Days 2-7: 0.1mg/kg sid with food

Essential, at least in the early stages.

Thalidomide Dose: 50-100mg at night. CANNOT BE USED IN PREGNANT CATS as it is teratogenic.

AntibioticsCefovecin (Convenia, Pfizer) OR Clindamycin (Antirobe, Pfizer)

8mg/kg subcutaneously every 14 days

5mg/kg bid for up to 6 weeks

Repeat treatments are likely to be needed.

Feline interferon omegaSubcutaneous 1 million units/kg s/c e.o.d. for 5

injections for cats presenting acutely. Dramatic improvement in terms of eating and reversal of cachexia, but for longer term results, other treatments often also required.

Subgingival feline interferon omega

1 million units (0.1ml of a 10 million unit vial) locally into the junction between healthy gum and diseased gum given when the cat is anaesthetised.

Thereafter monitor FCV shedding and reduce frequency of injections until cat stops shedding virus and a comfortable state has been achieved.

Reported to have excellent results although requires general anaesthetic and likely repeated treatments If the cat is a poor anaesthetic risk an alternative may be preferable.

Reconstituted solution can be kept in the fridge for up to 3 weeks, or can be kept frozen for longer.

Oral IFN omega 100,000 units given daily Doesn’t consistently give recovery, though may ameliorate clinical signs

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Choosing a vaccine for an FCGS-recovered cat

Having just spent months curing a cat with FCGS, the last thing you want to do is cause the disease to recrudesce when it comes to vaccine time. This could happen for these reasons:

iatrogenic re-infection by vaccinal FCV the FCV in the vaccine triggering the immune reaction of FCGS

In vaccinating my own FCGS-recovered cat, I wanted the vaccine to be inactivated or antigen only – NOT living FCV to protect the cat against as many field strains of FCV as possible to not cause his mouth to regress

It is not advisable to vaccinate FCGS recovered cats with a live FCV vaccineRadford et al (2000) found that the FCVs isolated from the cat in 4 of 20 vaccine failure cases were very similar to the FCV given in the vaccine. Live FCV vaccines can cause accidental FCV infection through aerosolisation or accidental contamination of the fur at the site of vaccination – the vaccinal virus may then be ingested as the cat grooms himself. Vaccination against feline panleukopenia virus (FPV) and feline herpesvirus (FHV) is often inseparable from vaccination with FCV and previously guardians of recovered cats were advised not to risk booster vaccination in case it caused recrudescence of FCGS clinical signs. However, where a cat has never had a primary vaccine course and is in a situation deemed to be at risk of FPV or FHV then an FCV vaccine needs to be given – this was the situation the author found herself in in 2008. Thus for this criterion, my choice of vaccine narrowed down to Purevax (Merial) which contains antigens (the FeLV component of this vaccine was already my preferred choice due to lack of adjuvant), or Fevaxyn (Zoetis, formerly Pfizer) which is inactivated: other vaccines were live.

Vaccination may not protect against up to 90% of field strains of FCVFCV is an RNA virus in which genetic mutation and recombination readily give rise to antigenic variants (Coyne et al, 2007), the viral replication cycle can be as little as 6 hours. Within every cat infected with FCV a Darwinian evolutionary race begins between the virus and its host – calicivirus is an RNA virus capable of fast rates of mutation and recombination and it rapidly changes antigenically in an effort to out-manoeuvre the cat’s ability to make neutralising antibodies and clear the infection (Radford et al,1998). This was demonstrated in an experiment by Radford et al (1998) who took a laboratory strain of FCV and passed it in cell culture 95 times – the virus after 95 passages was remarkably similar to that put into the first culture. However, the same strain of FCV put into a living laboratory cat evolved rapidly – in less than 39 days the virus had changed such that it was no longer neutralised by antibody the cat had developed, and the cat had to respond immunologically all over again to the new strain of FCV which had emerged. Usually the cat wins this evolutionary arms race – the half life of FCV shedding is 75 days. However sometimes the virus wins - some cats remain

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FCV carriers for years – the virus having successfully found an antigenic niche that the cat’s immune system seems unable to recognise (Coyne et al 2007). Most FCV carriers are asymptomatic. FCV vaccination may ameliorate clinical signs of FCV, but does not prevent asymptomatic carrier states.

It is believed that the process described above in an individual cat has been repeated on a national scale, resulting in strain diversity such that the FCV strains used in vaccines are not likely to protect equally well against all field strains, especially in countries where vaccines are used widely (Lauritzen et al, 1997; Hohdatsu et al, 1999; Weeks et al, 2001). Lauritzen et al, (1997) found that antisera to FCV strain F9, which was the most effective candidate vaccinal strain in the 1950s, by the 1990s only neutralised only around 10% of field strains from the UK, where vaccine uptake had been very good, and only 43% of American FCV strains. Therefore new vaccinal FCV strains are required regularly.

Antisera to FCV strains G1 and 431 protect against a wider range of field isolates than antisera to FCV F9This brings us to the second criterion for choosing a vaccine for an FGS recovered cat – which vaccine would protect against the most strains of FCV that could be encountered in the field? One hundred and ten UK field FCV isolates were neutralised in vitro by antisera against 4 vaccinal FCV strains: 255, F9, G1 and 431 (Addie et al, 2008). For the second criterion of protecting against the most field strains, the vaccine choice again narrowed down to Purevax (Merial) which contains strains G1 and 431, or Fevaxyn (Zoetis) which contains FCV strain 255.

Strains of FCV from FCGS cats are unusually difficult to neutraliseWithin the 110 isolates were 24 strains which had come from cats with FCGS – the results are presented in table 3. As we saw above, Knowles et al (1991) established that there is not one special strain of FCV which causes FCGS: the FCV strains which arise in each cat are peculiar to that cat. As in a previous study (Poulet 2000), FCGS FCV strains were more difficult to neutralise (even with antisera from cats not suffering from FCGS) and indeed antisera to the oldest vaccine strain, F9, failed to neutralise all but one isolate. Antisera to newer vaccine strains were better able to neutralise FCGS isolates. Individual cats have different abilities to recognise different antigens, therefore the more strains of FCV contained in a vaccine, the better the chance of that vaccine containing antigens the cat can respond to immunologically.

In vitro, antisera to FCV strains G1 and 431 (Purevax RCP Merial) also neutralised more virulent systemic FCV strains than did antisera to older vaccine strains (Poulet et al, 2008). Although recent studies indicate that assessing vaccine efficacy by the ability of antibodies to neutralise virus in cell culture probably underestimates the efficacy of the vaccine in real life - because the cat is also protected by cell mediated, as well as humoral, immunity (Lesbros et al, 2013) – it still seems desirable that a vaccine should elicit neutralising antibodies against the most FCV strains possible. Poulet et al, (2008)

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demonstrated correlation of in vitro neutralisation and in vivo protection against experimental infection.

Having many strains of FCV in the vaccine maximises the cats’ chances of immunologically “seeing” the vaccineSince cats are an outbred population, individual cats have different abilities to recognise different antigens, therefore the more strains of FCV contained in a vaccine, the better the chance of that vaccine containing antigens that the cat can respond immunologically. A dual-strain feline calicivirus vaccine stimulates broader cross-neutralization antibodies than a single-strain vaccine (Huang et al, 2010). Therefore Purevax was the best of the vaccines available to me (though had a Japanese vaccine containing three new FCV strains (Masubuchi et al, 2010) been available to me at the time I might have chosen that).

Vaccination could theoretically cause a FCGS-recovered cat to relapse – which vaccines are safe?FCGS is not a condition of immune deficiency – it is a condition of an exaggerated immune response: histopathological sections of the mucosae of such lesions are full of immune cells – plasma cells and lymphocytes – hence the previously used name lymphocytic, plasmacytic gingivostomatitis. We know that the immune response of a cat with FCGS is abnormal, with an imbalance in the inflamed gingivae and palatoglossal folds towards a mixed Th1 and Th2 instead of a predominantly Th1 response (Harley 1999). What was completely unknown was what would happen to an FCGS-recovered cat when he or she encountered FCV again (whether naturally or in the form of a vaccine)? Would his reaction just be normal, or would vaccination incite an inappropriate immune response and inflammation? Would vaccination trigger a whole new episode of FCGS? There was only one way to find out – to try vaccinating my cat.

One FCGS recovered cat was vaccinated with FCV strains G1 and 431 with no adverse effectsA middle-aged, male neutered domestic shorthair cat had recovered from FCGS following extraction of all but his canine teeth, subgingival recombinant feline interferon omega (Virbagen Omega, Virbac) and a change to a natural cat food (Wild Kitty Cat Food, www.wildkittycatfood.com, USA). He had been rescued and was of unknown vaccination status. in January 2008, the cat was vaccinated twice with Purevax RCP, he received the third part of his primary course in January 2009 and a booster Purevax RCP vaccine 3 years later, in 2012. During that entire time, his mouth has remained free of inflammation: vaccination with Purevax RCP did not cause the inflammation of his mouth to recur.

So far as this author is aware, this is the first documented report of a FCGS recovered cat being vaccinated against FCV. However, he is just a single case – more studies are required both to establish with certainty that this vaccine is completely safe to use in

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cats cured of FCGS and also to examine whether or not the vaccine actually has a protective role against FCGS developing.

NOTE: FCV vaccination does NOT work therapeutically and should not be given to a cat with active FCGS.

Table 3. Ability of antisera against 4 FCV vaccinal strains to neutralise field FCV isolates from 24 cats with FCGS

FCV strains 255 F9 G1 431Antisera 1 2 3 4 5 6 7 8Percent of isolates neutralised

37 17 4 4 12 46 42 71

Can gingivitis be prevented by brushing cats’ teeth?

Ingham et al stated: “Toothbrushing reduced gingivitis on the buccal tooth surface to some degree, although the effect was not as marked as anticipated.”

Conclusion NSAIDs and complete extraction of all of the teeth except the canines remain the treatments of choice for FCGS, but are not without risks and, despite treatment, some cats will remain symptomatic. Un-responsive cases may respond to recombinant feline interferon omega given subgingivally or orally. All cats suffering from FCGS should be taken off pro-inflammatory cereal based foods, even those coming under a “veterinary” label, and given a varied diet more natural to the cat: ie. containing real meat and fish (though ensure adequate calcium intake, especially in kittens with developing bones, and avoid feeding too much vitamin A and thiaminase in fish). One recovered case has been safely fully vaccinated with a calicivirus vaccine containing antigens of FCV strains G1 and 431. Further work is required to establish safe guidelines for vaccinating FCGS-recovered cats.

Help FCGS research

Please watch the catvirus.com webpage on FCGS for when we need volunteers for research. At present, we would really like to hear from any veterinary surgeons interested in searching their practice databases for information on vaccines and subsequent FCV related disease. In addition, it would be useful to hear of experiences you have had vaccinating cats post-FCGS. To join my email group, email “FCGS group” to draddie@catvirus.com

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References, further reading and useful websites

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