|Treatment of aggressive periodontitis
For figures, tables and references we refer the reader to the original paper.
Aggressive periodontitis comprises a group of rapidly progressing forms of periodontal disease that occur in otherwise clinically healthy individuals. It is accepted that, compared with patients with chronic periodontitis, patients with aggressive periodontitis show a more rapid attachment loss and bone destruction that occurs earlier in life. The patient's age when attachment loss is detected is often the criterion used by clinicians to diagnose aggressive periodontitis and to distinguish aggressive periodontitis from chronic adult periodontitis [reviewed by Albandar in this volume of Periodontology 2000 ]. Typically, aggressive periodontitis runs in families (familial aggregation), pointing towards a genetic predisposition. These three features (i.e. rapid attachment loss, bone destruction that occurs early in life and familial aggregation) are considered to be the primary features of this disease. In the Workshop for a Classification of Periodontal Diseases and Conditions, the secondary features of aggressive periodontitis were identified as (i) relatively low amounts of bacterial deposits despite severe periodontal destruction, (ii) presence of hyper-responsive macrophage phenotypes, and (iii) increased portions of Aggregatibacter actinomycetemcomitans and Porphy-romonas gingivalis . Recently an entire volume of Periodontology 2000 was devoted to the differences in clinical  and histopathological  features, epidemiological patterns , microbiological  and immunological [29, 81] aspects, and genetic and environmental risk factors  between aggressive periodontitis and chronic periodontitis. From these reviews it becomes clear that there are indeed major differences between aggressive periodontitis and chronic periodontitis. Despite these major differences, it is not always easy to differentiate these two disease entities clinically. However, from a research perspective, it is essential that these diseases can be, and are, clearly distinguished in order to gain a complete understanding of their etiology and pathogenesis . Also, as pointed out throughout this review, from a treatment perspective, distinction is of major importance. Additionally, patients with aggressive periodontitis are often diagnosed as having a localized form or a generalized form of disease. Each form has its own typical clinical features. The relative lack of clinical inflammation, often associated with the localized molar-and-incisor form of aggressive periodontitis, has been recognized for almost 100 years. It is generally accepted that this form of the disease is most often associated with a thin biofilm, at least in its early stages. In contrast, the presence of clinical inflammation in generalized aggressive periodontitis appears to be similar to that observed in chronic periodontitis. In this situation, age of onset and familial aggregation are important additional criteria for either diagnosis or classification. It is also becoming more commonly recognized that chronic periodontitis may occur simultaneously with both localized and generalized forms of aggressive periodontitis (reviewed in reference ).
The overall treatment concepts and goals in patients with aggressive periodontitis are not markedly different from those in patients with chronic periodontitis. Therefore, the different treatment phases (systemic, initial, re-evaluation, surgical, maintenance and restorative) are similar for both types of periodontitis. However, the considerable amount of bone loss relative to the young age of the patient and the high rate of bone loss warrants a well-thought-through treatment plan and an often more aggressive treatment approach, in order to halt further periodontal destruction and regain as much periodontal attachment as possible. The ultimate goal of treatment is to create a clinical condition that is conducive to retaining as many teeth as possible for as long as possible.
Diagnosis and treatment planning
Given the rapid progression of the disease and the high degree of difficulty in gaining control of the disease, diagnosis and treatment of aggressive periodontitis should preferably be carried out by a periodontist. However, the general practitioner does play an essential role in the early detection of patients who potentially have aggressive periodontitis. For a proper diagnosis, a thorough review of the patients' medical history, medications, family history and social history is required. In addition to an anamnesis, screening tests can be performed to establish systemic modifying factors such as diabetes and hematological conditions. Should a systemic disease be present, for instance poorly controlled diabetes, specialist medical consultation should be sought. Furthermore, risk factors, such as smoking and stress, must be identified.
The diagnosis should be made based on the above-mentioned criteria and considerations, together with a thorough mapping of the periodontal condition, which includes the recording of probing pocket depths, clinical attachment levels, bleeding on probing, furcation involvement, suppuration and tooth mobility, and an assessment of the patients' level of oral hygiene. These data, together with a radiological analysis, are of utmost importance for screening and for establishing the proper diagnosis and a differential diagnosis. The diagnosis will also be a clear starting point for proper treatment planning, for evaluating and explaining treatment effects to the patient and for patient education.
It is important to realize that even the most aggressive and advanced cases of periodontitis are treatable. Case reports have been published with a follow-up of up to 19 years for patients with localized aggressive periodontitis  and a follow-up of up to 40 years for patients with generalized aggressive periodontitis . However, it is essential for the patient to be highly compliant and highly motivated to do his part in order to gain control of the disease. A concerted effort must therefore be made by the clinician to inform the patient about the severity of the disease and the risk factors, and the role of the patient in the treatment. Also, the patient must be instructed very precisely about the necessary oral-hygiene measures. Furthermore, the clinician must assist the patient in controlling risk factors, such as smoking.
Considerable evidence points to a familial aggregation of aggressive periodontitis [discussed by Vieira & Albandar in this volume of Periodontology 2000 ]. Therefore, it is the practitioners' duty to inform the patient of this aspect and at least suggest screening other family members once the diagnosis has been established. The patient should be asked about the periodontal condition of their close relatives and, if possible, these relatives should seek consultation with a periodontist [11, 66].
Treatment of aggressive periodontitis starts with patient education and ensuring patient compliance. A considerable amount of time should be invested in establishing a good patient–clinician relationship. The time devoted to this, before commencing any form of active treatment and during the whole process of periodontal therapy, will have an impact on treatment success that should not be underestimated. The patient should be clearly informed about the disease process, contributing factors, the different phases and goals of the treatment, the predictability of treatment success and the patient's own crucial role in the treatment. The patient should be aware that, for success, it is essential for optimal compliance in plaque control and maintenance and for possible modifiable risk factors to be addressed. If the clinician doubts the compliance of the patient, several pretreatment visits could be included in the treatment plan, in which compliance with oral-hygiene instructions can be monitored and enhanced, together with compliance towards, for example, a smoking-cessation protocol.
Owing to the aggressive nature of the disease, clinicians are often faced with teeth that are severely periodontally compromised. The prognosis of these teeth needs to be discussed with the patient when setting up a treatment plan . One of the most difficult aspects is whether or not to extract a tooth. It is often stated that retention of hopeless teeth, but also of teeth with a doubtful prognosis, can compromise the treatment outcome. Leaving residual pockets of ≥6 mm is a risk factor for the progression of periodontal disease after active treatment . Residual deep pockets are niches in the mouth where considerable numbers of pathogenic bacteria can remain, even after treatment. Earlier studies have reported the disappearance of pathogenic bacteria from the mouth after extraction of compromised teeth, thus preventing recolonization of other teeth . A protective effect of extracting such compromised teeth has been identified in young children . It is therefore suggested that a more radical extraction protocol is justified when treating patients with aggressive periodontitis. However, the use of high-sensitivity bacterial-detection techniques has indicated that even after a full-mouth tooth extraction, periodontal pathogens remain in the mouth. Van Assche et al.  performed a full-mouth tooth extraction in nine patients and took microbial samples of subgingival plaque, the tongue dorsum and the saliva before extraction, and samples of the tongue dorsum and the saliva 6 months after extraction. Using a quantitative PCR analysis, the authors showed that, although tooth extraction resulted in significant reductions in the numbers of periodontal pathogens, it failed to eliminate the pathogenic species from the mouth . A study by the same authors investigated the microbial ecology in the newly formed pockets around implants placed in patients 3–6 months after a full-mouth tooth extraction. They showed that as soon as 1 week after abutment connection, the detection frequencies of pathogenic bacteria around the newly placed implants had risen to detection frequencies comparable with those before extraction. The bacterial numbers, however, were lower than before extraction . As a full-mouth extraction of periodontally compromised teeth does not result in the elimination of pathogens from the mouth, the extraction of compromised teeth in the dentate patient will probably not result in sufficient protection from recolonization around other teeth. Thus, extraction of teeth should not be advocated for preventing colonization around other teeth in the mouth.
Although the ultimate goal in the treatment of aggressive periodontitis is to create a clinical condition that is conducive to retaining as many teeth as possible for as long as possible, this is obviously difficult because patients with aggressive periodontitis are considerably younger than the average patient with chronic periodontitis. This age aspect interferes with treatment and treatment planning at different levels, some of which are not often considered.
One level is the psychological impact of the message that multiple teeth need to be extracted in young patients. Whilst there are currently no studies that address this aspect in patients with aggressive periodontitis, there are some indications that the impact of tooth loss on people and their lives should not be underestimated. Davis et al.  reported that in a cohort of 94 fully edentulous patients, 45% reported retrospectively to have experienced difficulties in accepting their tooth loss. In the cohort of Naik & Pay , which comprised 400 fully and partially edentulous patients, ‘only’ 25% of the patients reported having difficulties in accepting the loss of their teeth. One of the major differences between both studies was the age of the patients, which was above 60 years in the study by Naik & Pay  but of a wider range (31 years and older) in the study by Davis et al. . It cannot be directly derived from the latter paper whether younger patients experience more coping problems than do older patients, but it could be a reasonable hypothesis. Additionally, one should take into account that the patient's attitude toward tooth loss might be different in different parts of the world. Similarly, one could hypothesize that the compromised esthetics after periodontal therapy might have a significant effect on the general and psychological well-being, self-esteem and daily social life of younger patients.
Another level on which age impacts treatment in aggressive periodontitis is the prosthetic rehabilitation. Obviously, when teeth are extracted, the patient will seek adequate prosthetic rehabilitation. Although teeth can have a life expectancy of over 80 years, there is currently no single type of prosthetic device with a similar life expectancy. This means that the age of the patient when a tooth/teeth are extracted can play a decisive role in the patient's quality of life. Early extraction of a putatively questionable tooth in a 40-year-old patient with a life expectancy of 80 years could mean the start of time-consuming and expensive prosthetic treatment for the next 40 years [30, 51, 74]. However, when considering that several studies have demonstrated that compromised teeth can survive for decades, given that a proper maintenance program is followed. In this regard, Graetz et al.  followed 34 patients with aggressive periodontitis and 34 patients with chronic periodontitis, who had two or more teeth with alveolar bone loss of ≥50%, for 15 years. After 15 years they found that in the patients with aggressive periodontitis, 88.2% of the teeth with a questionable prognosis and 59.5% of the teeth with a hopeless prognosis had survived . These authors did not find any significant difference in tooth-survival rate between patients with aggressive periodontitis and patients with chronic periodontitis. It has been suggested that teeth with a predicted questionable prognosis as a result of severe bone loss should not be treated periodontally, but rather extracted early to avoid possible involvement of neighboring teeth. In regard to this aspect, it has been shown that long-term preservation of hopeless teeth is an attainable goal with no detrimental effect on the adjacent teeth . The treatment of periodontally compromised teeth that have advanced bone loss is a meaningful, therapeutic approach to prevent tooth loss with the consequence of prosthetic rehabilitation. Several studies have been performed in which the prognosis of dental implants in periodontally healthy subjects has been compared with the prognosis of dental implants in subjects with aggressive periodontitis. De Boever et al.  placed implants in, and followed up, 110 patients. Sixty-eight of these patients had suffered from chronic periodontitis and 16 from generalized aggressive periodontitis. After a follow-up period of 100 months in which the patients were enrolled in a maintenance program, there was a significant difference in implant survival between the chronic periodontitis and generalized aggressive periodontitis groups, with implant-survival rates of 96% and 80%, respectively . Swierkot et al.  evaluated the prevalence of mucositis and peri-implantitis, implant success and implant survival in patients treated for generalized aggressive periodontitis, over a period of 5–16 years, comparing them with periodontally healthy subjects. They found that patients with generalized aggressive periodontitis had a five times greater risk of implant failure, a three times higher risk of developing mucositis and a 14 times greater risk of developing peri-implantitis . Similarly to these studies, Mengel & Floris-de-Jacoby  studied 39 patients over a 3-year period following implant placement: 15 patients were treated for generalized aggressive periodontitis, 12 for chronic periodontitis and 12 patients were periodontally healthy. The results showed that the increase in pocket depth and attachment loss was greater, and the implant-survival rate was lower, for subjects with generalized aggressive periodontitis than for periodontally healthy subjects or patients with chronic periodontitis . From the aforementioned studies it can be concluded that implant survival in patients with generalized aggressive periodontitis is lower than in periodontally healthy subjects, or even in patients with chronic periodontitis. For localized aggressive periodontitis specifically there is very little evidence on which to base any conclusions. Clinicians should be aware of this when they consider implant-supported restorations for replacing teeth in patients with aggressive periodontitis, especially as patients with aggressive periodontitis are generally of a younger age than are patients with chronic periodontitis. This means that dental restorations need to remain functional and retain good esthetics for a longer period of time in these patients. Consulting with other dental specialists to assess the strategic restorative value of certain teeth or to assess alternative restorative options, such as orthodontic treatment, might help in the final decision of whether to extract or to retain.
Active periodontal treatment
Despite better insights into the etiology of aggressive forms of periodontitis, initial treatment is directed toward the bacterial load in the periodontal pockets. As such, there is no difference between the treatment concepts used for treating chronic periodontitis or aggressive periodontitis. However, the clinical response to nonsurgical therapy is much less documented for aggressive periodontitis than for chronic periodontitis. The number of studies assessing the effect of periodontal treatment on aggressive periodontitis is limited and they often report on only a small number of patients. This primarily relates to the low prevalence of this disease, and this hampers the execution of comparative clinical trials.
Although the effect of nonsurgical treatment on chronic periodontitis is well documented , its effect on aggressive periodontitis is much less clear. In relation to the effect of nonsurgical therapy alone as a treatment for aggressive periodontitis, two aspects seem of importance. The first aspect relates to the question of whether, and to what extent, scaling and root planing alone can result in the desired clinical changes, such as probing pocket-depth reduction, gain in clinical attachment and reduction in bleeding on probing. Ideally, this aspect is derived from data on the magnitude of the effect on the clinical parameters (e.g. the amount of probing pocket-depth reduction) combined with data on the predictability (e.g. the proportion of patients responding to treatment). Unfortunately, the latter is often not reported. The second aspect relates to the long-term stability of the results obtained. For this, longitudinal data are necessary.
For localized aggressive periodontitis, the effect of nonsurgical therapy alone can be derived from studies in which scaling and root planing represent the first phase of a staged combination therapy. In this regard, Slots & Rosling , evaluated 20 deep pockets in six patients with localized aggressive periodontitis and reported a small reduction of 0.3 mm in the probing pocket depth 16 weeks after scaling and root planing. However, this reduction was accompanied by a small average loss, of 0.05 mm, in clinical attachment. Similarly to these observations, Kornman & Robertson  reported an average probing pocket-depth reduction of 0.1 mm in eight patients, 2 months after scaling and root planing. This virtual absence of clinical response is, however, contradicted by data from comparative studies in which scaling and root planing alone represented the control treatment of the study. Reporting on 19 patients with localized aggressive periodontitis, Palmer et al.  showed an average reduction of approximately 0.8 mm in probing pocket depth and an average gain in clinical attachment of approximately 0.3 mm for the affected teeth, 3 months after scaling and root planing. Also, a reduction in bleeding on probing was observed. Asikainen et al.  even reported an average probing pocket-depth reduction of 1.4 mm in eight patients, 2 months after scaling and root planing. Unfortunately, none of the above-mentioned studies performed a statistical analysis of the observed effects. However, Ünsal et al.  analyzed the clinical effect of scaling and root planing alone in nine patients with localized aggressive periodontitis included in the control group of their study. Three months after performing scaling and root planing, pocket-depth reduction of 1.8 mm and clinical attachment gain of 1.2 mm was recorded. These effects were accompanied by a significant reduction in bleeding on probing, from 47.1% to 10.1%. Although the average probing pocket depth was not provided by Saxén et al. , it is interesting to note that the four patients with localized aggressive periodontitis in the control group of the study who did not receive surgery, showed a significant reduction in the percentage of sites with a probing pocket depth of >4 mm, from 19.4% at baseline to 2.8% 20 months after scaling and root planing. These findings are in line with those reported by Gunsolley et al. , who recalled 19 treated and 21 untreated patients with localized aggressive periodontitis, approximately 4 years after initial therapy. Some of the treated patients also received open flap curettage but, according to the authors, there was no significant difference in response between both groups of treated patients. Although no statistical comparison between the baseline and the recall data (approximately 4 years after baseline) was performed, the clinical data show, for the treated patients, a reduction in probing pocket depth of 0.2 mm and a gain in clinical attachment of 0.3 mm. Interestingly, probing pocket depth was increased by an average of 0.2 mm, and an additional loss of attachment of 0.3 mm was recorded for the untreated patients with localized aggressive periodontitis.
These limited data and statistical analyses on the effect of scaling and root planing in patients with localized aggressive periodontitis hamper a solid conclusion on its effectiveness and long-term stability. However, based on these data, it seems that scaling and root planing improves the clinical parameters in patients with localized aggressive periodontitis, which contradicts the reports from the 1980s. Its predictability is unknown, but the clinical effects can be recorded for up to 3 years after treatment.
The effect of root planing alone on generalized aggressive periodontitis is much better documented, although only one study has been specifically designed to assess the effect on clinical parameters. Hughes et al.  re-evaluated 79 patients with generalized aggressive periodontitis, 10 weeks after scaling and root planing. They reported statistically significant mean changes in overall probing pocket depth of 0.4 ± 1.7 mm, and of 2.1 ± 2.0 mm for initially deep pockets. An overall gain in clinical attachment of 0.2 ± 1.93 mm was also recorded, and for deep sites this was 1.77 ± 2.15 mm. The percentage of bleeding on probing was reduced by 34%. Interestingly, the authors reported that 32% of the patients did not respond to treatment. Probably, this large proportion of nonresponders can explain the large standard deviation values observed in this study. The nonresponding patients were primarily smokers. The observation that scaling and root planing indeed reduces clinical probing pocket depth and bleeding on probing, and results in a gain of attachment, is also confirmed by several comparative studies investigating the adjunctive effect of antimicrobials where the control group was treated with scaling and root planing alone [1, 7, 12, 34, 36, 37, 62, 76, 82, 88, 103, 106, 107] (Table 1). These studies show average whole-mouth probing pocket-depth reductions ranging from 0.7 to 1.5 mm, and average gains in clinical attachment ranging from 0.2 to 1.4 mm. For the majority of these studies the clinical changes were statistically significant. These results confirm the effectiveness of scaling and root planing in patients with generalized aggressive periodontitis, at least for the short term. In most of these studies the outcome of scaling and root planing was assessed, for the first time, 2–6 months after the baseline measurements had been performed. However, some studies followed the clinical results over time, up to 24 months after scaling and root planing, and the data from these studies can provide important information on the stability of the clinical results obtained. The majority of these studies show that the probing pocket-depth reductions [1, 12, 36, 37, 88, 103, 107] and gains in clinical attachment [1, 12, 34, 36, 37, 88, 103] remain stable or improve, up to 6 months after the initial therapy (Table 1). However, in some studies, there is already a small relapse in probing pocket-depth reduction [34, 82, 106] or a gain in clinical attachment [82, 106, 107] between 3 and 6 months after scaling and root planing. Studies with longer follow-up [36, 88] show that after 6 months, probing pocket depths start to increase and the obtained gain in clinical attachment starts to decrease (Table 1). These findings are again in agreement with those reported by Gunsolley et al.  who recalled 28 treated and 20 untreated patients with generalized aggressive periodontitis, approximately 4 years after initial therapy. Although no statistical comparison was performed between the baseline data and the recall data, the clinical data show an increase in probing pocket depth of 0.3 mm and a loss in clinical attachment of 0.4 mm for the treated patients.
Based on these observations, it seems that generalized aggressive periodontitis responds well to scaling and root planing in the short term (up to 6 months). However, after 6 months, relapse and disease progression is reported, despite frequent recall visits and oral-hygiene reinforcements.