Systemic implications of periodontal disease

Published 08/04/2021

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Periodontal disease is the most common infectious disease found in small animals with a prevalence that approaches 80%; prevalence increases with age and diminishes as body size increases – it is much more common in smaller animals compared to those of medium and large size.

. Intra-oral radiographs are essential when assessing dogs and cats with possible periodontitis. Note the loss of alveolar bone around the affected teeth.

Key points

Periodontal disease is the most common infectious disease found in small animals.

It has been suggested that periodontal disease can be a major factor in various systemic illnesses including cardiovascular problems, reproductive disorders, liver disease and diabetes.

Various hypotheses have been suggested as to how periodontitis may influence systemic disease but as yet there is no definitive proof of a link.

Periodontal disease can be prevented by meticulous removal of bacterial plaque with tooth brushing and oral hygiene.

Introduction

Periodontal disease is the most common infectious disease found in small animals with a prevalence that approaches 80% 1; prevalence increases with age and diminishes as body size increases – it is much more common in smaller animals compared to those of medium and large size 1. The periodontium comprises the gingiva, cementum, dental alveolar ligament and alveolar bone, which together contribute to the support of the tooth. Periodontal disease is caused by bacterial plaque, and can be subdivided into two parts: gingivitis and periodontitis. Gingivitis is a reversible inflammation of the gums, because once the cause (bacterial plaque) has been removed, the inflammation recedes. Periodontitis, on the other hand, is an irreversible inflammatory condition of non-gingival tissue (the alveodental ligament, cementum and alveolar bone) and is assessed by measuring the loss of attachment of the tooth. Periodontitis may be either inactive (quiescent), where there is no evidence of gingival inflammation (and if there has been loss of tooth attachment this may have occurred some time previously), or active, where there is ongoing destruction of tissue (Figure 1). Although it is recognized that periodontitis is an infectious disease, and more than 700 bacterial species have been identified as being capable of colonizing the biofilm of the subgingival sulcus, Koch’s postulates* do not apply 2.

* 1. The microorganism must be found in abundance in an animal suffering from the disease, but should not be found in healthy animals. 2. The microorganism must be isolated from a diseased animal and grown in culture. 3. The cultured microorganism should then cause disease when introduced into a healthy animal. 4. The microorganism must be re-isolated from this experimentally infected animal and identified as being identical to the original causative agent.

Figure 1. Active severe periodontitis in a dog. © Dr.De Simoi

Gingivitis, even if untreated, does not always result in periodontitis; the development of periodontal disease is in fact determined by an imbalance between the bacterial population and the host immune system. Immune capability, stress, age, nutritional and metabolic status, breed and endocrine disease are all factors that may aid or prevent the progression of periodontal disease. If the disease progresses, the bony destruction and apical migration of the supporting connective tissue will cause loosening and eventual loss of one or more teeth.

Periodontal disease is a focal infection. This concept, introduced more than a century ago, describes a localized, chronic disease, which represents a source of microorganisms, toxins, and products of bacterial and tissue degradation, capable of reaching distant organs and tissues 3. The surface area involved in periodontitis has been measured in affected toy breeds and found to range between 3.18-29.8 cm² 4 and so the area of diseased tissue can represent a considerable proportion of the dog’s total body surface area.

During the development of periodontitis the bacteria present in periodontal pockets can reach the bloodstream, causing bacteremia, and, although in healthy individuals these are intercepted by the reticuloendothelial system 5, the continuous prolonged exposure to bacteremia may be associated with systemic disease associated with distant organs and systems 6 7. The systemic implications of periodontal disease are not, however, limited to the bacterial load. Inflammatory chemical mediators, bacterial endotoxins and toxins from tissue degradation can also be involved, either by direct harmful effects or because they cause immune reactions in organs distant to the oral cavity.

Cardiovascular implications

More than 50 studies in human medicine have been published examining the relationship between periodontal disease and cardiovascular disease (CVD), and most of them agree that there is a direct correlation between the two. For example, constituents of periodontopathic bacteria were detected in atherosclerotic plaques 8, whilst other studies concluded that there is a significant correlation between periodontal disease and CVD 9 10.

The same is true in veterinary medicine, where studies have also demonstrated a positive correlation between the presence of periodontal disease and histopathologic changes affecting the heart and other internal organs 4 5 6 711 12 13 Nevertheless, international scientific opinion is not unanimous on the importance of oral infections in the genesis of systemic disease; this is because there is currently no conclusive evidence of a direct link between periodontal disease and other diseases 14.

Reproductive disorders

It has been shown that pregnant women with periodontitis are up to 7.5 times more likely to give birth prematurely, and for their babies to have low birthweight. This finding correlates with the increase in pro-inflammatory cytokines triggered by circulating bacterial lipoproteins. In some cases periodontopathic bacteria were detected directly within the amniotic fluid 15.

Diabetes mellitus

High circulatory levels of inflammatory chemical mediators such as interleukin 6 (IL6), tumor necrosis factor (TNF) and C-reactive protein (CRP) may increase insulin resistance and thus prevent correct control of blood glucose in diabetic patients. One report noted that treating periodontal infection in a diabetic dog allowed subsequent control of blood sugar levels with insulin therapy 16.

Liver disease

Hepatic degeneration, steatosis, and intrahepatic abscesses have been described and associated with periodontitis in both humans and dogs 7. A recent publication noted that liver function tests improved after periodontal therapy in humans, and reported that infection with the bacteria Porphyromonas gingivalis may be a risk factor in the development and progression of hepatic steatosis and steatohepatitis 17.

Etiopathogenic hypotheses

Given that it is difficult to clearly identify the mechanisms that link oral and systemic disease, different hypotheses have been proposed to explain this relationship, namely direct infection, systemic inflammation with endothelial damage, and molecular mimicry between bacterial antigens and autoantigens.

Direct infection hypothesis

Bacteria such as Streptococcus spp., Staphylococcus spp., P. gingivalis and their byproducts can cross the vascular barrier and enter the systemic circulation. A transient bacteremia has been demonstrated after chewing and tooth-brushing and during dental prophylaxis and surgery; however bacteremia is generally of little or no clinical significance in healthy subjects. It was, however, demonstrated experimentally that bacteremia with P. gingivalis induces the appearance of atherosclerosis in susceptible pigs and mice. Several periodontopathogens were then isolated either directly or recognized through PCR in organs and tissues at sites distant to the oral cavity. A recent study showed that P. gingivalis was present in 100% cases of atherosclerotic plaques in humans 18 19.

Systemic inflammation hypothesis

According to this hypothesis periodontitis causes an increase in circulating cytokines which can directly damage the endothelium of blood vessels, leading to the formation of lesions that affect the heart and other internal organs. It has been demonstrated that pro-inflammatory cytokines such as TNF and IL6 can cause anabolic mutations in myocytes through the activation of intracellular signals leading to myocardial hypertrophy 20. In several studies high levels of CRP have been observed in cases of chronic periodontitis 21 whilst one recent study 22 demonstrated that people who underwent intensive periodontal therapy (scaling and root planing) had significantly reduced elasticity of their brachial artery 24 hours post-therapy when compared to a control group. This was related to the increase in CRP and IL6 during periodontal therapy. However 60 and 180 days after the dental work, the vascular elasticity was significantly greater in the group subjected to periodontal therapy compared to the control group; this increase was attributed to the beneficial effects of the periodontal treatment.

Molecular cross-reactivity hypothesis

According to the molecular cross-reactivity hypothesis the development of systemic disease is the consequence of an immune response induced by bacterial heat-shock proteins (HSPs). All cells (including endothelial cells) which are subject to stress in various forms express HSP, and bacterial HSPs are a further antigenic challenge during infections. The immune system is not always able to distinguish between bacterial and autologous HSPs, so that during a periodontitis infection cross-reactive T-lymphocytes are activated and antibodies are produced which may cause an autoimmune response to antigenically similar host tissues 23. In the case of atherosclerosis it has been demonstrated that endothelial cells express a human HSP called HSP60; however several periodontopathic bacterial species have also been found to produce their own HSP60 which is very similar to the autologous stress protein. The bacterial HSPs induce the synthesis of targeted antibodies which may attack the host cells. Several studies have shown that periodontal infection may contribute to atherosclerosis and cardiovascular disease through molecular mimicry mechanisms 24 25.

Diagnosis of periodontal disease

Generally, periodontal disease starts with few or no clinical signs and the main reason for the owner to request an evaluation of the oral cavity is because their pet has developed halitosis. Accurate diagnosis cannot be based solely on visual inspection of the oral cavity; general anesthesia followed by a periodontal examination involving the use of a probe (Figure 2) and intraoral radiography is essential. Various periodontal probes are available but all are designed to allow pocket depth measurement and assessment of gingival hyperplasia or recession. With the probe one can also evaluate the degree of tooth mobility and the presence of furcation lesions in double or triple rooted teeth (Figure 3). The probe should be gently introduced into the gingival sulcus (Figures 4-5), ideally evaluating 4-6 points around the circumference of each tooth; apparently healthy buccal teeth may have deep pockets either palatally or lingually. All observations must be recorded on a dental chart in order to provide an overall assessment.

Figure 2. A periodontal probe with colored bands to allow measurement of gingival pocket depth. © Dr. De Simoi

Figure 3. A furcation lesion; the probe can be easily inserted between the roots of the tooth. © Dr. De Simoi

Figure 4. On examination a probe should be gently introduced into the gingival sulcus at 4-6 points around the circumference of each tooth; note how the depth varies with this tooth. © Dr. De Simoi

Figure 5. On examination a probe should be gently introduced into the gingival sulcus at 4-6 points around the circumference of each tooth; note how the depth varies with this tooth. © Dr. De Simoi

Prevention and treatment of periodontal disease

Periodontal disease can be prevented by meticulous removal of bacterial plaque with tooth brushing and oral hygiene. Some commercial diets may help in reducing coronal plaque but the crucial factor is the removal of subgingival plaque. The aim is not to sterilize the oral cavity but to prevent the bacterial biofilm changing from a mixed commensal population dominated by aerobic bacteria to a population that is predominantly anerobic. Treatment of periodontal disease should be performed with the animal anesthetized and the trachea intubated; once the arcades have been accurately charted and intra-oral radiographs have been analyzed (Figures 6-7) supra- and subgingival scaling is performed, followed by more complex procedures such as tooth extraction or periodontal surgery as indicated.

Figure 6. Intra-oral radiographs are essential when assessing dogs and cats with possible periodontitis. Note the loss of alveolar bone around the affected teeth. © Dr. De Simoi

Figure 7. Intra-oral radiographs are essential when assessing dogs and cats with possible periodontitis. Note the loss of alveolar bone around the affected teeth. © Dr. De Simoi

Antibiotic usage

Severe and extensive periodontal disease in an otherwise healthy subject should not be treated with antibiotics long term; the correct treatment is to remove the cause (plaque, tartar, irreparably compromised teeth) by scaling the teeth and performing tooth extraction as necessary. Antibiotics should be used for two main purposes: to treat local infection and to prevent bacteremia.

Treatment of local infection

If periodontal disease has caused osteomyelitis of the maxilla or mandible, antibiotic therapy is recommended, starting a few days before surgery and continuing for several weeks afterwards. The use of antibiotics a few days before surgery is also indicated where ulcerative gingival lesions have developed (even if there is only a small accumulation of plaque), in cases of chronic ulcerative paradental stomatitis in dogs (Figures 8a and b), and in cats with stomatitis.

Figure 8a. Ulcerative gingival lesions in a dog with chronic ulcerative paradental stomatitis. © Dr. De Simoi

Figure 8b. Ulcerative gingival lesions in a dog with chronic ulcerative paradental stomatitis. © Dr. De Simoi

Prophylaxis of bacteremia

Bacteremia is common in patients with active gingivitis and periodontitis, from normal daily activities such as grooming and chewing of food. In healthy subjects this is quickly countered by the activity of the reticuloendothelial system. In the case of periodontitis patients with serious systemic disease such as heart problems, subjects with joint or eye replacements, splenectomized subjects or with hyperadrenocorticism, and when cellular metabolism is depressed by systemic disease, the risk that tissues distant to the mouth may be affected justifies the use of perioperative antibiotics. In these cases the choice is a broad-spectrum bactericidal antibiotic that can be administered intravenously at induction of anesthesia and repeated if the operation lasts more than two hours. It is also possible to administer a single dose orally on the morning of the surgery.

Conclusion

At present there is no unequivocal evidence of a direct relationship between periodontal disease and systemic effects, even though there are various hypotheses that explain the relationship between the two conditions. However, much evidence suggests that periodontal disease may promote and maintain inflammation in organs distant to the mouth, and that even in the early stages of periodontitis the body can react with the synthesis of acute phase proteins, thereby demonstrating the stimulation of a systemic disease induced by inflammation within the oral cavity.

The health of the periodontium is not only important for the maintenance of the teeth. Periodontal disease can have a significant impact on overall health and may be responsible for morbidity and mortality, especially in certain susceptible dog breeds. Preventive measures such as oral hygiene, the use of chew toys, and the feeding of products specifically designed to reduce the accumulation of bacterial plaque and calculus should be considered when managing periodontitis. Dental health food products typically consist of a kibble with a conformation and structure that deliver a mechanical abrasive action, but some products also contain sodium polyphosphate which will chelate the salivary calcium, slowing the mineralization of plaque and consequently the formation of tartar. These foods may therefore be recommended as an aid in a general plan to reduce the risk of periodontal disease.

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Alessandro De Simoi

Alessandro De Simoi, Clinica Veterinaria Feltrina, Feltre, Italy Read more