Aggressive periodontitis

Aggressive periodontitis describes a type of periodontal disease and includes two of the seven classifications of periodontitis as defined by the 1999 classification system:

Localized aggressive periodontitis
Generalized aggressive periodontitis

LAP is localised to first molar or incisor interproximal attachment loss, whereas GAP is the interproximal attachment loss affecting at least three permanent teeth other than incisors and first molar. The prevalence of LAP is less than 1% and that of GAP is 0.13%. Approximately 0.1% of white Caucasians and 2.6% of black Africans may have LAP. Estimates of the disease prevalence are 1-5% in the African population and in groups of African descent, 2.6% in African-Americans, 0.5-1.0% in Hispanics in North America, 0.3-2.0% in South America, and 0.2-1.0% in Asia. On the other hand, in Asia, the prevalence rate of 1.2% for LAP and 0.6% for GAP in Baghdad and Iran population, and 0.47% in Japanese population.
Therefore, the prevalence of LAP varies considerably between continents, and differences in race or ethnicity seem to be a major contributing factor.
Aggressive periodontitis is much less common than chronic periodontitis and generally affects younger patients than does the chronic form. Around 1 in every 1000 patients experience more rapid loss of attachment. Males seem to be at higher risk of GAP than females
The localized and generalized forms are not merely different in extent; they differ in etiology and pathogenesis.

Etiology

Microbiology

Of the microflora characterised in aggressive periodontitis, approximately 65-75% of bacteria are Gram-negative bacilli, with few spirochaetes or motile rods present. Aggressive periodontitis is often characterised by a rapid loss of periodontal attachment associated with highly pathogenic bacteria and an impaired immune response. Various studies have associated Aggregatibacter actinomycetemcomitans, formerly known as Actinobacillus actinomycetemcomitans, with aggressive periodontitis. An early study dating back to 1983 explains its prevalence and documents its role in localised aggressive periodontitis.
Virulence factors are the attributes of microorganisms that enable it to colonise a particular niche in its host, overcome the host defences and initiate a disease process. Fives Taylor et al. have categorised the virulence factors of Aggregatibacter actinomycetemcomitans as follows.

Promote colonization and persistence in the oral cavity:	Interfere with host defences:	Destroy host tissues:	Inhibit host repair of tissues:
Adhesins	Leukotoxin	Cytotoxins	Inhibitors of fibroblast proliferation
Invasins	Chemotactic inhibitors	Collagenase	Inhibitors of fibroblast proliferation
Bacteriocins	Immunosuppressive proteins	Bone resorption agents	Inhibitors of bone formation
Antibiotic resistance	Fc-binding proteins	Stimulators of inflammatory mediators	Inhibitors of bone formation

Samaranayake notes the evidence for the specific involvement of Aggregatibacter actinomycetemcomitans includes: an increased incidence of it found in subgingival plaque obtained from lesional sites, high level of its antibody which tends to fall following successful treatment, its possession of a wide range of potentially pathogenic products and its elimination with concordant disease regression, following treatment with successful periodontal therapy and adjunctive tetracycline.
Porphyromonas gingivalis is a Gram-negative anaerobe associated with the pathogenicity of periodontal disease, and aggressive periodontitis is no exception. Greater numbers of both Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were found in active, destructive periodontal lesions in comparison to non-active sites.
Capnocytophaga spp are implicated as prime periodontal pathogens, especially in localised aggressive periodontitis. Both Capnocytophaga spp and Prevotella intermedia were the most frequently detected microorganisms in a study, which also noted that Capnocytophaga spp was the most prominent bacteria in subgingival samples of patients with aggressive periodontitis.
An impaired ability of peripheral blood lymphocytes to react to chemotactic stimuli is found in the majority of patients with aggressive periodontitis. As well as Aggregatibacter actinomycetemcomitans being associated with this, the synergism of the disease also accounts for both Capnocytophaga spp and Porphyromonas gingivalis.

Pathophysiology

Aggressive periodontitis is a multifactorial disease with many complex interactions including host factors, microbiology and genetics.
Host defences involve multiple factors; saliva, epithelium, inflammatory response, immune response and chemical mediators. The inflammatory exudate in the gingival tissues and gingival crevicular fluid is mostly polymorph neutrophils but also includes B cells and plasma cells. The neutrophils may show an intrinsic functional defect and respond abnormally when challenged by certain pathogens. The plasma cells produce specific antibodies in response to the periodontal pathogens, which diffuse into the gingival crevicular fluid. They produce mainly IgG, with some IgA. It has been suggested that these gingival crevicular fluid antibody levels could be potentially useful in the development of a vaccine. Patients with localised aggressive periodontitis have large amount of Aggregatibacter actinomycetemcomitans specific IgG2. This is suggested to be protective against wider spread periodontal breakdown. However, patients with generalized aggressive periodontitis have decreased ability to mount high titres of IgG to Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans.
It has also been found that a low T-helper to T-suppressor ratio is found in aggressive periodontitis which may alter local immune regulation. Monocytes respond to bacterial and inflammatory stimuli with very high levels of local release inflammatory mediators and induce hyper-inflammatory reaction with activation of tissue degrading matrix-metalloproteinases. These is also evidence they produce increased amounts IL-1α and IL-1β which cause osteoclastic bone resorption. These amounts are greatly reduced following treatment.
Studies of families, twins and sibling pairs have provided strong evidence for a genetic basis for aggressive periodontitis. A person's genetic predisposition to the condition is determined by a single gene of major effect, inherited as an autosomal dominant trait. However, for the disease process to initiate the person must be exposed to the presence of periodontal pathogens and potentially also various environmental factors.
Smoking is a generalized risk factor for generalized forms of aggressive periodontitis. Studies found that smokers have more affected teeth than non-smokers and high levels of attachment loss. This is due to the suppression of serum IgG2 and antibody against Aggregatibacter actinomycetemcomitans found in smokers.

Features

According to the 1999 International Workshop for the Classification of Periodontal Diseases, aggressive periodontitis was defined according to 3 primary features, in contrast to chronic periodontitis. These features are common for both localized and generalized form of disease.

Primary features

Patients are clinically healthy.

Patients do not have any underlying systemic disease that would contribute to aggressive periodontitis. For instance, diabetes is proved to be associated with periodontitis- it is a major risk factor when glycaemic control is poor.

The rate of loss of attachment and bone loss is rapid.

Loss of attachment refers to the destruction of periodontium whereas the bone refers to the alveolar bone supporting the teeth. The loss can be determined by using a calibrated periodontal probe and taking radiographs of the dentition. Usually the loss of attachment is greater than 2mm per year.

Aggressive periodontitis runs in the patient's family.

Familial aggregation of aggressive periodontitis is often discovered by taking a thorough medical history of the patient. The patient is said to have a high genetic susceptibility to aggressive periodontitis. Many studies have shown that genetic factors contribute to the pathogenesis of this disease. In this case, the manifestation of aggressive periodontitis is believed to be the result of genetic mutation, combined with environmental factors.

Secondary features

Secondary features are characteristics which are frequently seen but not always present in every patient diagnosed with aggressive periodontitis.

The severity of periodontal tissue destruction is out of proportion to amount of bacteria present.

The amount of bacteria is often indicated by the level of dental plaque. This feature implies that when aggressive periodontitis is present, loss of attachment and bone loss tend to occur even if the plaque level is low.

High levels of Aggregatibacter actinomycetemcomitans and, in some populations, Porphyromonas gingivalis.

These gram-negative microbes are considered the chief aetiological agent of aggressive periodontitis. They are implicated in the development of aggressive periodontitis by triggering inflammatory response in periodontal tissue.

There are abnormalities associated with phagocytes.

Phagocytes are essential in resolving inflammation. The impairment of their phagocytic activity results in persistent inflammation in periodontal tissues.

Hyper-responsive macrophage phenotype.

Due to the increased responsiveness, the macrophages produce excessive levels of inflammatory mediator and cytokine, such as prostaglandin E2 and interleukin-1β. Their hyperactivity is associated with periodontal tissue destruction and bone loss.

Progression of attachment loss and bone loss may be self-arresting.

In some patients, the disease may burnout without any cause-related therapy.
Caries levels have seen to be lower in cases of aggressive periodontitis.
Staging
Cases of aggressive periodontitis have been staged into Stage I, II and III based on the severity of the cases. The staging index was proposed based on clinical features, radiological features and possible risk factors. The proposed index was validated with 10 cases of aggressive periodontitis followed for 10 years.