John R. August, BVetMed, MS, MRCVS, DACVIM
Painful oral inflammation provides difficult diagnostic and therapeutic challenges in cats, due to our poor understanding of many causes of the problem and poor patient and owner compliance during treatment. Clinical signs may vary from mild gingivitis to refractory gingivostomatitis (GS) affecting most of the soft tissues of the oral cavity. The prevalence of the problem in primary-care practice in the United Kingdom recently was reported as 0.7%.1
Signalment and History
Less commonly, kittens may be affected with marginal gingivitis that occurs at the time of eruption of their deciduous teeth. Characteristic gingival hyperemia and swelling may be more common in Abyssinian, Persian, and Somali kittens, and may regress spontaneously or persist indefinitely.
GS manifests most commonly in adult cats, often at about 7 years of age. Although the number of affected cats was relatively small, a recent study demonstrated possible peaks of incidence at 1-5 and 10-13 years of age.1 No gender predispositions have been reported; however, some cat breeds (for example, those predisposed to the juvenile form of the disease) may develop more severe lesions.
Historical signs associated with GS include dysphagia, including dropping food, preferring soft foods, swallowing food whole rather than chewing, and chewing on one side of the mouth; anorexia, often associated with weight loss; ptyalism, sometimes hemorrhagic; poor body condition and unkempt haircoat due to cessation of self-grooming; and signs of pain, including reluctance to be petted and medicated, pawing at the mouth, and subtle changes in behavior including reclusiveness and inactivity. Without treatment in most patients, the lesions are progressive; however, on rare occasion, the disease may go into spontaneous remission. Approximately 35% of in-contact cats in multiple-cat facilities will develop lesions within 1-3 years of diagnosis of an initial case of GS.2
General anesthesia is necessary for a comprehensive oral examination in cats with GS, because of the pain associated with oral manipulation. Most commonly, affected cats have a degree of oral inflammation that is disproportionally more severe than can be explained by the level of dental disease and calculus accumulation.1 Two major sites of involvement within the oral cavity have been described, the buccal mucosa overlying the premolar and molar arches (buccostomatitis), and the glossopalatine mucosa (palatoglossitis).3 Affected tissues include the gingiva, glossopalatine arches, lateral pharyngeal folds (fauces), buccal mucosa, pharynx, hard palate, tongue, and lips.4 Lip-fold pyoderma may be noted in some cats with chronic oral infections and ptyalism.2 In general, lesions may be noted in any oral tissue with direct contact with plaque antigens. Pharyngeal involvement may be explained by the accumulation of plaque on the base of the tongue and the high concentration of lymphoid tissue in that area.4
In comparison to gingivitis induced solely by infection, as an early component of periodontal disease in which gingival inflammation only affects the buccal and labial arches, gingival inflammation in GS completely surrounds each tooth.5 Findings on oral examination include ulceroproliferative lesions along the buccal and gingival mucosa, often more severe toward the caudal aspect of the mouth.1 A more guarded prognosis should be given for patients with more exaggerated lesions in the caudal oral cavity.5 Submandibular lymphadenopathy is common in chronically affected cats. As noted below, the presence of concurrent periodontal disease and tooth resorptions in many cats with GS complicates diagnosis and management.
GS in cats likely is a multifactorial disease, involving individual predispositions to adverse sequelae from an inappropriate immunologic response to antigens in the oral cavity. Antigens that have been incriminated in the pathogenesis of the disease include plaque bacteria, feline calicivirus (FCV), and food proteins. It has been proposed that it may be the sum total of stimulation from several antigens, rather than a reaction to one individual antigen, that triggers the development of GS in cats.3
Compared to unaffected cats, patients with GS have decreased salivary immunoglobulin (IgA) and increased IgM.4 Increased serum and salivary IgG are noted in most affected cats. A polyclonal serum gammopathy is seen commonly in cats with GS, and may be associated with the upregulation of interleukin 6 that has been observed in affected patients.6
Unique Role of Plaque
Although a variety of antigens have been incriminated in the pathogenesis of GS in cats, an adverse reaction to bacterial plaque antigens (plaque intolerance) may be the most important inciting factor. This is based on observations that control of bacterial plaque is absolutely essential for the management of the disease in most patients.4
The oral cavity is an ideal environment for the incubation of a wide variety of bacterial species, being warm, moist, and bathed in nutrient-rich saliva.7 Evaporation of saliva on exposed tooth surfaces leaves a glycoprotein layer (pellicle) that traps aerobic bacteria. As the film matures, aerobic and facultative rods are trapped on the surface. Oxygen tensions in the deeper layers of the film then allow growth of anaerobic organisms. Finally, spirochetes start to multiply in an environment that is enriched by inflammatory by-products associated with active gingival inflammation.7 The incorporation of calcium phosphate and calcium carbonate into the biofilm will result in the formation of calculus within 2-3 days of initial plaque formation.7 Control of oral bacteria occurs naturally through the activity of salivary components including IgA, lactoferrins, and lysozyme, and through mechanical removal from normal occlusal rubbing.7 The pathogenetic role of decreased salivary IgA levels in cats with GS is not well understood. Lesions of GS in the caudal oral cavity may fail to resolve following extraction of all teeth (on whose surfaces plaque is deposited) because plaque remains on the tongue, or concurrent adverse immunologic reactions to infectious agents persist.
Considerable controversy and confusion persist about the role of infectious organisms in the pathogenesis of GS in cats. This potential relationship is complicated by the fact that the infectious organisms suspected of playing a role in the pathogenesis of GS may be isolated from apparently healthy cats. A recent study of one household of cats showed no direct association between clinical cases of GS and test results for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), FCV, feline herpesvirus 1 (FHV-1), and Bartonella spp.8
On the other hand, there is clinical evidence that chronic shedding of FCV may play an important role in the development of some cases of GS. Of 25 cats with chronic GS, 22 (88%) were found to be shedding FCV and FHV-1 in their saliva.9 The results of this study contrast with the clinical experience of many clinicians who do not identify such a high rate of FHV-1 shedding. Cessation of FCV shedding coincided with a spontaneous resolution of GS in one patient; however, changes in diet at that time could have played a role in the improvement of clinical signs.10 Extraction of all teeth in cats with GS who are shedding FCV will cause remission of signs in some patients.3 A small cohort of these patients, however, will not resolve following extractions, suggesting that FCV may play a role in the perpetuation of the disease. Cases of GS with concurrent FCV shedding are not thought to be due to unusually pathogenic strains of the virus. Rather, the rapid antigenic and genetic changes in the virus may result in escape from the immune system and persistence of infection.3 It has been proposed that FCV replication may be the result of tissue damage and suppression of immune responses from the GS, leading to enhanced virus replication.4 From a clinical standpoint, however, cats that are infected concurrently with FCV and FIV are more likely to develop GS.11
A unifying model has been proposed recently for the role of these various agents in the pathogenesis of GS in cats.4 Individual abnormalities in the components of saliva lead to impaired mucosal defense mechanisms and altered epithelial integrity. An exaggerated response develops to persistent viral infections and plaque antigens, exacerbated by tissue damage from periodontal disease.
Chronic GS in cats rarely occurs in isolation, and a meticulous oral examination often reveals other related and unrelated causes of pain and inflammation. Failure to identify and address these concurrent conditions is an important cause for treatment failures of GS.
As noted earlier, an exaggerated immunological reaction to plaque antigens may be central to the development of GS in cats. Many cats diagnosed with GS for the first time are middle-aged at presentation, and often have concurrent clinical and radiographic evidence of periodontal disease. Visible dental disease was present in 70% of cats with GS in a recent study; however, severe dental lesions were not noted in any affected cats.1
Tooth resorptions were noted in 59% of a cohort of cats with chronic GS, compared to 48% of control cats without GS. There was no significant difference in incidence of resorptions between the two groups.9 Characteristic areas of focal gingival hyperplasia and pain associated with tooth resorptions are easy to miss when diffuse ulceroproliferative lesions of GS and periodontal disease are present. Failure to address tooth resorptions and retained tooth roots that may harbor bacterial infection complicates the control pain and inflammation when treating cats with GS.
Diagnoses that must be considered include periodontal disease, neoplasia (most commonly squamous cell carcinoma or fibrosarcoma), opportunistic microbial infections secondary to persistent FeLV or FIV infections, uremic stomatitis, linear granulomas and eosinophilic ulcers, and autoimmune diseases. Although oral lymphoma is rare in cats, lesions may resemble those of chronic GS.4
A thorough history and physical examination should be completed to identify any systemic diseases that might contribute to the patient's oral lesions. A complete blood count, serum chemistries, and urinalysis should be performed; however, these tests are frequently low-yield or reveal expected results such as hyperglobulinemia. Tests for FeLV p27 antigen and FIV antibody are indicated for all patients with GS. The author takes cultures or PCR tests for FCV from the glossopalatine folds and gingival margins on all patients with GS as part of initial baseline evaluation. Anaerobic bacterial cultures from the gingival sulcus have been recommended for cats with chronic refractory GS.12
Dental radiographs should be performed following a meticulous oral examination under anesthesia. Documentation of radiographic evidence of periodontal disease, tooth resorptions, missing teeth, and endodontic disease is important for prognosis and treatment planning.12 Follow-up radiographs after tooth extractions are necessary to ensure that no root fragments remain.
In most patients, a strong suspicion of GS is acquired based on signalment and history, the visual identification of symmetric ulceroproliferative lesions affecting the gingival and palatoglossal mucosa, and lack of previous responses to routine dental prophylaxis. The need to biopsy tissues in all cases is debatable; however, the procedure is indicated whenever tissue changes are asymmetric or atypical in order to exclude neoplasia or unusual inflammatory disorders.
Biopsy findings reveal the presence of plasma cells, with smaller numbers of lymphocytes, neutrophils, and macrophages.6 Two histopathologic forms of the disease have been described; a dense, band-like submucosal lymphocytic-plasmacytic infiltrate, or chronic active inflammation of the mucosa and submucosa which also includes a neutrophilic infiltrate.4 It is important to remember that lymphocytic-plasmacytic gingivostomatitis is a histopathologic diagnosis, rather than a definitive clinical diagnosis. Identification of the inciting antigens is necessary to complete the diagnostic process.
Principles of management of chronic GS in cats include pain control, removal of plaque from all oral surfaces, control of gingival and dental infections, removal of teeth involved in the disease process, initial control of inflammation with corticosteroids, and eradication of other inciting antigens, when possible.
Patient appetite, behavior, and compliance with medication is improved when oral pain is controlled satisfactorily. Transmucosal oral buprenorphine (10-15 μg/kg q8-12h) may be used for this purpose. Antimicrobial treatment should follow meticulous dental prophylaxis, and extractions as indicated. Antimicrobials prescribed should be effective against gram-positive aerobic and gram-negative anaerobic oral bacteria, and should concentrate in soft tissues and bone.4 Suitable choices include amoxicillin-clavulanic acid, clindamycin, and metronidazole. Unfortunately, antimicrobial efficacy declines over time as plaque reaccumulates on the crowns of the teeth. Stringent home hygiene with oral antimicrobial rinses (chlorhexidine gluconate) may slow the reaccumulation of plaque after dental prophylaxis, if patient compliance allows.
Ideally, the use of corticosteroids should be limited to control of initial inflammation to decrease discomfort, and to improve appetite and well-being. In the author's experience, oral methylprednisolone (1 mg/kg PO q12h, and then tapered to lowest effective dose) works most effectively, especially when administered as a compounded suspension. Unfortunately, the efficacy of corticosteroid treatment declines over time, associated with renewed deposition of plaque, the persistence of microbial infections in periodontal disease, and ongoing viral shedding in some affected cats. Shedding of FCV and resolution of clinical signs of GS both resolved in a cat treated with recombinant feline interferon omega.3 Further investigations are needed into the use of safe immunomodulating drugs for cats with GS.
All diseased teeth and teeth with resorptions should be extracted at the time of initial dental prophylaxis and dental radiography. Based on the theory that an adverse reaction to the deposition of plaque bacteria is central to the development of GS in cats, there is a growing consensus that additional extraction of healthy premolar and molar teeth improves outcome after more conservative medical strategies fail. Extraction of canine and incisor teeth may be necessary if initial extractions fail to resolve the inflammation. Sixty per cent of cats with GS were clinically cured after complete extraction of diseased teeth, teeth surrounded by severe buccostomatitis, and mandibular molar teeth and maxillary fourth premolar and first molar teeth in cats with faucitis.11 An additional 20% of the cats showed significant improvement; however, 7% of the patients showed no improvement at all. In the author's experience, patients in the latter group often are persistent shedders of FCV and may have more severe lesions in the caudal oral cavity and oropharynx. Knowing the FCV status of patients with chronic GS may assist in providing owners with a realistic understanding of the benefits and limitations of extensive dental intervention. Very unusually, cats with refractory GS may respond to a strict novel protein diet when lesions fail to improve after dental prophylaxis and extractions.
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8. Quimby JM, et al. J Fel Med Surg 2007, in press.
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