Chronic feline gingivostomatitis (GS)

is a frustrating disease to manage owing to its elusive, probably multifactorial, etiopathogenesis. It is estimated to affect up to 12% of cats [1]. It is a severe, immune-mediated oral mucosal inflammatory disease of cats, characterised by ulcerative and or proliferative inflammatory lesions lateral to the palatoglossal folds. Histologically the affected tissue is predominantly infiltrated with plasma cells and lymphocytes. Within the epithelium T lymphocytes predominate, and in the submucosa B lymphocytes predominate [2].

Etiology
Despite long term extensive investigations, the cause of GS remains uncertain. Many infectious agents have been implicated but absolute causality has not been established. In addition, non-infectious causes such as multicat living, dental disease, stress and hypersensitivity have been suggested [3].

• Viral: Implicated viruses include feline calicivirus (FCV), feline herpes virus (FHV-1), feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). Of these FCV seems the most consistently associated with GS. It has been found that 60% of cats with GS were FCV positive compared to only 25% of control cats [4].
• Multicat households: Multicat households, breeding catteries, shelters and free roaming behaviour are risk factors for feline viruses, but may also be a direct risk for GS. A recent study investigating the association between the number of cats in the household and prevalence of GS, found that each additional cat in the household increased the risk of GS by 70% [5]. It was postulated that a higher rate of viral cyclic reinfections and stress may be responsible.
• Periodontitis: The association between GS and periodontitis was demonstrated in a retrospective case control study [6]. Cases were more likely to have external inflammatory root resorption and retained roots, but fewer dental fractures than controls. Overall GS cases had more widely distributed and severe periodontitis than the control cats with other oral disease. This highlights that dental radiography is important in the assessment of GS cases, and the chronic inflammatory nature of periodontitis likely contributes to the cause of GS.
• Bacterial burden: Bacteria are thought to play a role in GS, but the route of this remains unknown. There seems to be less diversity in the oral microbiota in cats with GS and periodontitis than healthy cats, with more anaerobic and gram-negative species [7]; however, the implication of this finding is not understood
• Oesophagitis: 98% of GS cases in a recent case control study had concurrent oesophagitis [8]. The oesophagus was assessed endoscopically, although strangely, none of the cats showed any signs of GI diseased despite positive endoscopic findings. It is suggested that all cats with GS should be empirically treated for oesophagitis, especially as both diseases have similar clinical signs.

Treatment
Spontaneous resolution has not been reported in cats suffering from GS, therefore all cats will require some form of therapy.

Pain management:
Regardless of treatment employed, pain management is essential in all cases of GS. The most appropriate choice of analgesic therapy depends on concurrent disease and medication, patient compliance and perceived pain levels. Buccal buprenorphine has been shown to be well absorbed and significantly reduces pain in cats with GS [9], so is a good option for consideration if available.

Medical:
On its own, medical treatment typically does not carry favourable long-term outcomes. GS is a chronic immune mediated inflammatory disease and so the basis of medical treatment is immunosuppression and modulation.

Prednisolone can be used as a short term anti-inflammatory but owing to the adverse effects it should not be used in a long term capacity.

Recombinant feline interferon omega (rFeIFN-w)
disrupts viral replication and is already used in canine parvovirus, FIV and FeLV infections. It likely has action against FCV and FHV-1 and feline coronavirus. It may have a dual action- local immunomodulation and inhibition of viral (FCV) replication. Further studies are needed to quantify the efficacy of this treatment and the best route of administration.

Cyclosporin Is an immunosuppressive that works via inhibition of T cell activation. Several small studies have found positive response to treatment with cyclosporin, with 45% (5 of 11) cats being clinically cured after 3+ months of treatment [10]. Again, further larger studies are needed to quantify this effect.

Mesenchymal stem cells (MSC)
Have great potential in the treatment of immune mediated and inflammatory conditions owing to their potent immunomodulatory properties. These immunomodulatory effects are through the inhibition of T cell proliferation and alteration of B cell function. GS is characterized by T cell inflammation and dysregulated immune response, making it an ideal condition for the use of MSC therapy.

In a recent study, treatment was via 2 intravenous injections with autologous adipose derived MSC one month apart. This achieved clinical remission in 43% of cats and substantial improvement in 29% over a 6- 24 month follow up [11]. No recurrence occurred in this time following clinical remission.

Allogeneic MSC resulted in lower clinical efficacy, with 29% cases showing substantial improvement but only 29% showing clinical remission [2]. It should be noted that these studies were just small pilot studies involving only 7 cats in each. These studies are currently ongoing and have expanded into multi-center case control investigations. Stem cell isolation and expansion is a very specialist procedure so whilst results are promising this treatment may not be imminently widely available.

Surgical:
Partial (molars and premolars) or full mouth dental extraction provide substantial improvement or resolution of GS in around 50- 70% of cats [3]. However, 20-30% of cases showed minimal or no improvement, and even those cats with moderate improvement may require subsequent surgical (in the case of partial extractions) or on-going medical therapy

The extent of dental extractions does not seem to impact outcome, therefore partial extraction (plus other teeth clinically indicated), should be considered the best evidence based first line treatment for GS [3]. If there is no clinical response within 4 months, then full mouth extraction can be completed.

Nutrition
Cats suffering from GS often have poor appetites owing to the intensely painful lesions in their mouths. They may find it difficult to swallow or crunch kibble and so a wet food may be a better option for these cats such as Royal Canin Instinctive wet pouches. If the cat is underweight a very highly digestible diet such as RC Gastrointestinal wet pouches may be indicated. Cats having undergone a partial or full dental extraction can actually cope well with eating kibble once healing is complete. Immediately after surgery RC Recovery wet cans are recommended.

Summary
GS remains an incompletely understood condition affecting a huge number of cats seen in general practice. It is most likely caused by multiple factors- an inappropriate immune response possibly directed at viral stimulation. It may be exacerbated by environmental factors, in particular multicat households seem a significant risk factor.

First line recommended treatment is currently partial dental extraction, with around ¹/₃ cats achieving clinical remission after this, ¹/₃ substantial improvement and the final ¹/₃ not responding. New medical therapy in the form of MSC has shown promising results but is not as yet widely available. The absolute importance of pain management and appropriate nutrition in all cases of GS cannot be overestimated.

References

1. Winer, J.N., B. Arzi, and F.J. Verstraete, Therapeutic Management of Feline Chronic Gingivostomatitis: A Systematic Review of the Literature. Front Vet Sci, 2016. 3: p. 54
2. Arzi, B., et al., Therapeutic Efficacy of Fresh, Allogeneic Mesenchymal Stem Cells for Severe Refractory Feline Chronic Gingivostomatitis. Stem Cells Transl Med, 2017. 6(8): p. 1710-1722.
3. Lee, D.B., F.J.M. Verstraete, and B. Arzi, An Update on Feline Chronic Gingivostomatitis. Vet Clin North Am Small Anim Pract, 2020. 50(5): p. 973-982.
4. Thomas, S., et al., Prevalence of feline calicivirus in cats with odontoclastic resorptive lesions and chronic gingivostomatitis. Res Vet Sci, 2017. 111: p. 124-126.
5. Peralta, S. and P.C. Carney, Feline chronic gingivostomatitis is more prevalent in shared households and its risk correlates with the number of cohabiting cats. J Feline Med Surg, 2019. 21(12): p. 1165-1171.
6. Farcas, N., et al., Dental radiographic findings in cats with chronic gingivostomatitis (2002-2012). J Am Vet Med Assoc, 2014. 244(3): p. 339-45.
7. Rodrigues, M.X., et al., The subgingival microbial community of feline periodontitis and gingivostomatitis: characterization and comparison between diseased and healthy cats. Sci Rep, 2019. 9(1): p. 12340.
8. Kouki, M.I., et al., Chronic Gingivostomatitis with Esophagitis in Cats. J Vet Intern Med, 2017. 31(6): p. 1673-1679.
9. Stathopoulou, T.R., et al., Evaluation of analgesic effect and absorption of buprenorphine after buccal administration in cats with oral disease. J Feline Med Surg, 2018. 20(8): p. 704-710.
10. Lommer, M.J., Efficacy of cyclosporine for chronic, refractory stomatitis in cats: A randomized, placebo-controlled, double-blinded clinical study. J Vet Dent, 2013. 30(1): p. 8-17.
11. Arzi, B., et al., Therapeutic Efficacy of Fresh, Autologous Mesenchymal Stem Cells for Severe Refractory Gingivostomatitis in Cats. Stem Cells Transl Med, 2016. 5(1): p. 75-86.

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Written on November 11, 2021