Feline chronic gingivostomatitis current concepts in clinical management

Abstract

Practical relevance: Feline chronic gingivostomatitis (FCGS) is a debilitating disease for cats and a challenge for veterinarians and cat caregivers alike. Recent literature indicates that the disease is immune-mediated in nature and likely associated with a chronic viral infection in patients with higher alpha diversity of their subgingival microbiome. The immune-mediated nature of FCGS includes both local as well as systemic effects, and the transcriptomic analysis of affected patients supports these findings.

Treatment options: Localized therapy in the form of surgical extraction of all, or nearly all, teeth continues to be the mainstay of treatment. For cats that do not respond to surgical management, medical management, in the form of immunosuppressive or immunomodulatory therapy, remains an option. Analgesia is of fundamental importance. Immunomodulation utilizing mesenchymal stromal cell therapy provides an alternative treatment avenue for refractory patients and likely targets the chronic viral infection present in this disease. The potential for treatment stratification and use of novel systemic treatment options may be revealed as the molecular pathways involved in this disease are better described.

Aims: This review outlines current and emerging concepts linking available science pertaining to FCGS and clinical management of the disease.

Evidence base: The article draws on the best evidence base at this juncture and is also driven by the authors' collective experience of working on the disease for over a decade.

Keywords: Dentistry; gingivostomatitis; inflammation; medical therapy; oral mucosa; surgical therapy.

Figure 1

The clinical presentation of feline chronic gingivostomatitis (FCGS) can vary slightly, though the hallmark is inflammation that not only affects the gingiva but also extends to the alveolar and buccal mucosa. (a,b) A patient with refractory ulcerative FCGS also affecting the sublingual tissues. (c) A case showing both ulceration and proliferation. Note the proliferation on the right side affecting the buccal and sublingual mucosa. (d) A case of FCGS where spontaneous bleeding from the areas of ulceration was noted. (e) Concurrent inflammation of the gingiva and alveolar mucosa is typical of patients with FCGS and in this case surrounds the left maxillary fourth premolar tooth. (f) In this cat with FCGS there is mild inflammation on the left side of the buccal mucosa, while the right side has moderate inflammation

Figure 2

Innate immunity is the rapid and non-specific response initiated by antigen-presenting cells (APCs) at the site of an insult. Adaptive immunity takes days to weeks after the injury occurs, is highly specific and is sustained long-term. Adaptive immunity can also be tolerogenic. To activate lymphocytes, APCs travel to inductive sites including tonsils, salivary glands, lymphoid follicles and draining lymph. Effector sites include the epithelium, lamina propia and salivary glands. Activated and expanded lymphocytes migrate from the effector to inductive areas to mediate the immune response. T cells are believed to help during rapid responses of antigen recall by providing protective responses while preventing adverse allergic reactions. The primary function of CD4+ cells is helping to regulate other immune cells either directly or indirectly. In health, lymphocytes are predominantly a memory population

Figure 3

Histologic section from the buccal mucosa of a patient with FCGS. Note the hyperplastic epithelium and prominent rete pegs (finger-like structures) that extend deep into the submucosa. 20× magnification; bar = 20 urn

Figure 4

Histologic sections from the buccal mucosa and palatoglossal folds of a healthy cat (a,bi-iv), and from the gingiva and affected buccal mucosa of a patient with FCGS (c-f). LP = lamina propia; SE = subepithelium. (a) Buccal mucosa ((immunohistochemistry [IHC] stain of CD1c+; 600× magnification; bar = 40 μm). Note the intraepithelial dendritic cells demonstrating characteristic mature dendritic cell morphology (arrow). (b) Palatoglossal fold (400× magnification; bar = 40 μm): (i) note the subepithelial leukocyte clusters (arrow) (hematoxylin and eosin [H&E] stain); (ii) subepithelial collection of CD4+ T cells (IHC stain of CD4+); (iii) subepithelial cluster of CD1c+ denritic cells (IHC stain of CD1c+); (iv) subepithelial sets and diffuse MHC II+ cells (IHC stain of MHC II+). Reproduced from Arzi et al, with permission of Wiley and Sons. (c) Gingiva adjacent to teeth affected by FCGS (toluidine blue stain, 400× magnification). Note the submucosal mast cells (small black arrows), lymphocytes (black arrowheads), neutrophils (large black arrow), plasma-like cells (white arrows) and macrophage-like cells (white arrowhead). Reproduced from Arzi et al, with permission of Elsevier. (d) Abundant plasma cells, occasional Mott cells (ie, plasma cells that have spherical inclusions, or Russell bodies, packed in their cytoplasm) and proportionately fewer lymphocytes and neutrophils (H&E stain; 100× magnification). (e) Note how T lymphocytes cluster in the epithelium (IHC stain of CD3+; 100× magnification). (f) B lymphocytes are highly present in the submucosal compartment (IHC stain of CD20+; 100× magnification)

Figure 5

Intraoral radiographs of a 5-year-old domestic shorthair cat with clinically and histopathologically confirmed FCGS. (a) Occlusal view of the maxillary incisor teeth. (b) Occlusal view of the mandibular incisor teeth. (c) Right mandibular PM3 to M1. (d) Left mandibular PM3 and PM4. The radiographs demonstrate mild to moderate, semi-generalized horizontal alveolar bone loss (†) and type I tooth resorption (*) at the furcation of affected teeth, as well as a missing left mandibular first molar tooth and buccal bone expansion of the mandibular canine teeth

Figure 6

Evaluation of the systemic immune response of FCGS patients revealed hyperglobulinemia in 60% of patients, elevated circulating levels of IFN-γ,TNF-α and IL-lβ, neutrophilia in 30-40% of patients, as well as CD8+ effector memory cells. These findings mirror those of studies evaluating the local immune response

Figure 7

Schematic diagram summarizing the diagnostic and treatment recommendations for FCGS patients in the preoperative, intraoperative and postoperative periods. As discussed in the text, immunosuppressive therapy refers to the use of glucocorticoids to affect the immune response more globally (compared with immunomodulation, which refers to more targeted treatment of specific portions of the immune system via different types of medications). SDAI = Stomatitis Disease Activity Index; CBC = complete blood count; FeLV = feline leukemia virus; FIV = feline immunodeficiency virus; FCV = feline calicivirus; PFFV = puma feline foamy virus; PME = partial mouth extraction; FME = full mouth extraction; IFN = interferon