Treating the Inflamed Mouth

Judy Rochette Canada

A chronically inflamed mouth is a non-specific, clinical manifestation of multiple, different immune dysfunctions. Inconsistent success with any one treatment is due to trying to treat multiple diseases with just one �cure.� A basic understanding of the currently recognised causes for �stomatitis� may help the practitioner better tailor his treatment to the patient.

The oral tissues are constantly exposed to bacterial pathogens and antigenic proteins. In a healthy mouth, a balance is maintained between progression of disease and the host's immune system. Humoral and cellular immunity invokes the presence in the oral tissues of neutrophils, lymphocytes, plasma cells, interleukins, cytokines, prostaglandins, histamine, complement, kinins, helper and suppressor T-cells, natural killer cells, and antibodies. Any imbalance in the interactions involved in this complex protective mechanisms results in a disease state. Both inadequate and exuberant host responses have been identified as causes of stomatitis.

An inadequate host response to pathogens can be the result of an inherited or an acquired immune dysfunction. Feline juvenile gingivitis (Abyssinian, Persian), Chediak-Higashi (colour dilutes), or Grey Collie Syndrome have heritable neutrophil dysfunctions. Diabetes mellitus, immunosuppressive drugs, pregnancy, or cancer are examples of non-infectious, acquired immunosuppression. Infectious causes of immune dysfunction include the feline leukemia virus (FELV) and the feline immunodeficiency virus (FIV). Fifty-percent of FIV-positive cats suffer from stomatitis, likely due to a reduction in numbers and function of T-helper and natural killer lymphocytes.

Treatment of immunosuppressed animals must rely on ameliorating underlying disease, decreasing the pathogenic load, and supporting what immune response the host can mount. It is inappropriate to incorporate
agents that will further reduce host response to pathogens. Cytotoxic drugs, corticosteroids, griseofulvin (neutropenia), cyclosporine, and aurothiogluconate may appear to provide initial improvement because the inflammatory response is suppressed; however, antigenic damage is still occurring and once the medication is withdrawn, or even in the face of it, the inflammation will return.

At the other end of the spectrum is the exuberant host response. This type of response can also be divided into what are likely heritable sensitivities/allergies and a non-specific hyper-reactivity. Canadian Huskies and Malamutes show a breed predilection for eosinophilic granulomas and eosinophilic stomatitis. A familial, ulcerative stomatitis in Maltese dogs is recognised in Britain and the northeastern United States. These animals often need to be treated with potent immunosuppressive medications and doxycycline to control their oral disease.

In the feline world, there has been recent evidence that chronic antigenic stimulation and an inability to moderate the immune response are co-factors in the proliferation of the disease. Blood panels are usually normal in these animals with the exception of elevated immunoglobulins reflecting chronic stimulation. Some animals may show transient autoantibodies in their oral tissues during the acute phase of their disease, which disappear when the inflammation resolves. Food protein has been postulated to be one source of antigens. A higher than normal
prevalence of calici virus infection suggests that this virus plays a role in chronically stimulated animals. On a physiological level, several papers have indicated that a lack of, or dysfunction of, suppressor T-cells plays a role. Cytokines are also been implicated in magnifying a normal inflammatory reaction into an allergy-like reactivity. These latter papers do not suggest cause or treatment, but a better understanding of what truly occurs in the tissues of affected animals may ultimately lead us to more effective treatments.

Treatment for any animal suffering from stomatitis should involve some or all of the following:

 Assess a complete blood count, viral panel and chemistry panel and treat any underlying imbalance or disease.

 Perform a thorough prophylaxis. To minimise sites for bacterial recolonisation extract all compromised teeth (significant periodontal disease, fractured and/or non-vital teeth, teeth with resorptive lesions) and all retained root or tooth fragments, and flush with chlorhexidine. Oral cultures are usually non-productive. Biopsy any unusual or asymmetric lesion as a small percentage of cats have had metaplastic transformation of their oral disease into oral carcinomas. Give appropriate antibiotics and analgesics. Fentanyl patches may be necessary in some patients.

 Initiate a feeding trial with a hypoallergenic diet. Human studies have shown that food allergens can perpetuate oral inflammation. Human research has also shown that the flavours cinnaminase and benzoin, found in virtually every canned human and pet product due to their heat stability, and often not required to be listed individually on ingredient lists, may be significant contributors to the problem. Consider homemade diets.

 Encourage vigilant home care including daily tooth cleansing (brushing, swabbing), the use of a tartar-deterrent diet (Hill�s T/D, Friskies Dental Diet for Cats), chlorhexidine gels, impregnated discs (Stomadex), or rinses (Hexarinse, Nolvadent), hexametaphosphate-containing products (CET products), Maxiguard gel, Waltham's Dentabones, Tartar Chews and Nutribiscuits, etc. Home fluoride treatments are not recommended. The toxic dose for fluoride is 2 mg/kg and toxicity can be cumulative over several treatments. Fluoride is difficult to apply properly and also inactivates chlorhexidine.

Corticosteroids at immunosuppressive doses provide the best chance of successful treatment. Efficacy is best with dexamethasone>prednisolone>prednisone. Liquid formulations are usually easier for the owners to give than tablets, but injections may be best if the owners are comfortable with this method of treatment. There has been
little published about the efficacy of other agents such as azathiaprine.

Antibiotics such as amoxicillin with clavulanic acid, clindamycin, doxycycline, metronidazole, and enrofloxacin are efficacious against periodontal pathogens. Clindamycin, doxycycline, and metronidazole have
beneficial effects not related to their antimicrobial activity. Doxycycline perioceutic gel implanted into pockets could provide sustained effects against plaque bacteria.

Aurothioglucose can be used in the hyperresponsive patient. Gold compounds stabilise lysosomal enzymes, inhibit neutrophil and macrophage migration and phagocytosis, inhibit prostaglandin production and suppress immunoglobulin synthesis. Possibly of more importance, gold salts inhibit helper T-cell responses without affecting the suppressor T-cell population. When initiating gold therapy, the amount given should be increased gradually over several weeks until the appropriate dose is reached. Monitor CBC and biochemical profiles weekly initially. Watch for drug-induced stomatitis.

Oral cyclosporine inhibits lymphocyte activity and blocks the production of interleukin 2. The liquid should be diluted with vegetable oil to create a 2.0% solution. The published dose for cyclosporine ranges widely but 10 mg/kg q12h for both dogs and cats should be safe and efficacious. Divide the necessary volume into two equal aliquots and place one aliquot over each upper fourth premolar. As some variability in oral uptake of cyclosporine occurs, monitor blood levels weekly until 400�500 ng/ml is achieved. Toxicity may occur at levels in excess of this
concentration. Monitor renal function.

Non-steroidal anti-inflammatory agents (NSAIDs) provide both analgesia and an anti-inflammatory action. Piroxicam should not be used in immunosuppressed animals as it inhibits neutrophil function and migration. Side effects such as gastrointestinal disturbances and renal disease may limit their use.

Antihistamines such as amitryptyline, chlorpheniramine or diphenhydramine may help stabilise mast cell membranes and decrease the histamine released in an inflammatory reaction.

Oral bovine lactoferrin can be useful for immunocompromised animals as it improves neutrophil phagocytosis. The product comes in 350 mg capsules but is used at 40 mg/kg. If compounding is necessary, ensure that the lactoferrin is mixed with iron-free ingredients, as iron will inactivate lactoferrin.

Alpha interferon has immunomodulating and antiviral effects that have been shown to be useful in FELV and/or FIV patients. While cats will remain viremic, they improve clinically and hematologically. To prepare an interferon solution, dilute one bottle of 3 million units in 990 ml of lactated ringers solution (LRS). Mix well then divide all of this �mother stock� into empty, sterile 10 ml bottles or syringes and freeze all except one. The frozen mother stock will keep indefinitely. Take the remaining, non-frozen aliquot and add it to a second 990 ml bag of LRS. This is the �daughter stock� that you will dose with and which contains 30 international units per ml. Give one ml once daily by mouth for seven days on, seven days off, repeating indefinitely. The daughter stock can be stored for three to four months in the refrigerator.

Levamisole is an immunopotentiator at lower, intermittent doses, but becomes immunosuppressive with prolonged use. It has been shown to help normalise lymphocyte numbers and function and increase macrophage
phagocytosis in immunocompromised patients. The dose for dogs is 1�2 mg/kg per os every second day, and for cats is 25 mg per os, every second day for three treatments.

Selective or whole mouth extraction of teeth may be necessary for patients with faucitis and pharyngitis. The more distal the inflammation in the oral cavity, the harder it will be to correct. Many cats with faucitis will not respond to other therapies until all teeth distal to the canines are removed. Eighty percent of cats that could not be controlled by any other means were cured by whole mouth extraction. To suture extraction sites, use an absorbable suture such as chromic gut or other rapidly dissolving material.

Laser therapy has limited usefulness. Tissues initially appear to improve but the disease recurs. Electrocautery provides no therapeutic benefit to these mouths, and may do great harm. Radiation therapy as an adjunct to periodontal treatment does not provide any additional benefits over periodontal treatment alone. Consideration should be given to decreasing the frequency and/or number of vaccinations a patient receives. Chronic immune system stimulation may aggravate a hyperresponsive animal.

Whenever you are first presented with one of these patients, prepare the owner for an ongoing battle with a goal of control, not necessarily cure. Aim for comfort and pain relief, not necessarily maintenance of full dentition. Good luck.