Periodontology 2000, Vol. 53, 2010, 711 Printed in Singapore.

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2010 John Wiley & Sons A/S

PERIODONTOLOGY 2000

Comparative biology of chronic and aggressive periodontitis: introduction

G A R Y C. A R M I T A G E , M A R Y P. C U L L I N A N & G R E G O R Y J. S E Y M O U R

The overall aim of this volume of Periodontology 2000 is to compare the biological features of chronic and aggressive forms of periodontitis in order to identify similarities and differences between these phenotypic expressions of periodontal diseases. The contributors were asked to compare the features of chronic and aggressive periodontitis, with an emphasis on shared characteristics (i.e. similarities) and unique characteristics (i.e. differences). This task has been a formidable one, as many details of the etiology and pathogenesis of periodontal infections are unknown. In addition, studies dealing with these diseases often use different terminology and case denitions, thereby complicating any attempt at effective analysis of the existing literature (6). Indeed, all of the contributors to this volume of Periodontology 2000 expressed frustration about the inconsistent use of criteria to dene cases of the different forms of periodontitis in the periodontal literature.

Clinical features of chronic and aggressive periodontitis

The clinical features associated with periodontitis are the foundation upon which these periodontal infections have historically been categorized, classied and diagnosed (1, 3). This review limits its discussion to localized and generalized forms of chronic and aggressive periodontitis. It is argued that chronic and aggressive forms of periodontitis are different diseases because of important differences in the following clinical features: (i) age of onset or detection, (ii) rates of progression, (iii) patterns of destruction, (iv) signs of inammation, and (v) relative amounts of plaque and calculus. However, since localized and

generalized chronic periodontitis appear to share numerous clinical, epidemiological and etiological characteristics, they are considered to be slightly different manifestations of the same disease. In contrast, major clinical differences between localized and generalized aggressive periodontitis suggest that they are different diseases. The differences between the generalized chronic and generalized aggressive forms of periodontitis are less clear. From a clinical point of view, generalized aggressive periodontitis is characterized by widespread destruction of periodontal tissues in a young patient; the amount of destruction seen at an early age suggests a rapid rate of progression (i.e. high ratio of damage to age). Generalized chronic periodontitis is also characterized by widespread periodontal damage, but usually in an older individual; a slow rate of progression is assumed based on the relatively low ratio of damage to age. This distinction is important from a disease management perspective, as individuals with aggressive forms of periodontitis are in need of relatively urgent care.

Epidemiological patterns of chronic and aggressive periodontitis

A major problem in the literature dealing with chronic and aggressive forms of periodontitis is the absence of universally accepted case denitions that can be used by investigators who wish to study the epidemiology, etiology, pathogenesis and treatment of these diseases (6). As a consequence of this deciency, it is extraordinarily difcult to make valid comparisons from one study to the next.

Armitage et al.

Unfortunately, the 1999 classication system (1) did not identify unequivocal criteria for these muchneeded case denitions. Development of such denitions is a formidable task since they need to include a wide array of disease-associated variables such as: (i) type of damage (e.g. clinical attachment loss, radiographically assessed bone loss), (ii) severity of damage (e.g. slight, moderate or severe, based on the amount of clinical attachment loss), (iii) probing depths as a surrogate assessment of the potential habitat for periodontal pathogens, (iv) inammatory status of the tissues, (v) age of the patients, and (vi) extent of disease (e.g. number of sites teeth affected). Furthermore, for maximum utility, a case denition should be applicable to multiple aspects of the epidemiology, etiopathogenesis and management of periodontal infections. As a rst step towards resolving the case-denition problem in the periodontal literature, Demmer & Papapanou (6) propose case denitions for chronic periodontitis and generalized aggressive periodontitis that might be useful in epidemiological studies.

forms of periodontitis, and nd no apparent histopathological explanations for the different rates of destruction observed in chronic and aggressive forms of periodontitis.

Mechanisms and control of pathological bone loss in periodontitis

Bartold et al. (4) examined the mechanisms and regulation of bone loss associated with all forms of periodontitis, and found that the periodontal lesions of patients with chronic or aggressive periodontitis appear biochemically similar with respect to the molecular mediators and pathological processes that lead to bone loss. However, there are differences in the speed at which bone loss occurs, but the reasons for this are unclear. A better understanding of the host response and inammatory pathways leading to bone loss in chronic and aggressive forms of periodontitis may eventually lead to novel pharmacological methods for inhibiting the tissue destruction associated with these diseases.

Histopathological features of chronic and aggressive periodontitis

Chronic and aggressive forms of periodontitis both involve progressive destruction of the periodontium, and, if left untreated, eventual loss of the affected teeth. Among the major overlapping histopathologic events in both diseases are: (i) acute inammatory changes [e.g., vasculitis] in response to microbial colonization of the tooth, (ii) inux of neutrophils toward microbial components of subgingival biolms, (iii) detachment of the junctional epithelium and its conversion to pocket epithelium, (iv) inammatory destruction of connective tissue adjacent to the pocket epithelium, (v) accumulation of chronic inammatory cells, (vi) apical migration of the epithelium onto the tooth root, and (vii) osteoclastic resorption of alveolar bone. Tissues obtained from sites with chronic or aggressive forms of periodontitis appear identical when viewed using conventional light and electron microscopic methods. It is currently believed that most of the destruction found in all cases of periodontitis is mediated by host inammatory and immunological responses to subgingival biolms. In their review, Smith et al. (11) discuss and compare the nature of the inammatory inltrates found in cases of chronic and aggressive

Comparison of the microbiological features of chronic and aggressive periodontitis

In the past century, signicant advances have occurred in our understanding of the subgingival microbiota associated with periodontal infections. The ability to isolate putative periodontal pathogens by growing them on articial media in the laboratory has led to recognition of a widely accepted group of cultivable periodontal pathogens. In the current genomic era of exploration, it is now possible to detect and study the not yet cultivable components of the subgingival microbiota. Accordingly, the list of putative pathogens is growing, and now includes a very diverse group of microorganisms in both the Bacteria and Archaea domains. It is becoming increasingly apparent that periodontal infections are caused by a much more diverse microbiota than merely gram-negative anaerobes. Based on currently available data, it appears that the microbiota associated with localized aggressive periodontitis is somewhat different from that associated with either generalized aggressive or chronic forms of periodontitis (3). In addition, preliminary data from a limited number of studies suggest that the subgingival microbiota associated

Chronic vs. aggressive periodontitis

with cases of generalized aggressive periodontitis is signicantly different from that of chronic periodontitis. However, there are many microbiological similarities between the two diseases (2). A substantial proportion of the periodontally healthy population harbors some periodontal pathogens as part of their normal oral microbiota. In such cases, the host and the microbiota live in a mutualistic homeostatic relationship. Armitage (2) discusses emerging thoughts about the interaction of the oral microbiota with the host, and its relationship to maturation of the host innate and adaptive immune responses necessary for establishment of the host microbe homeostasis compatible with health. In addition, preliminary combined genomic and proteomic analyses of hostbiolm interactions have suggested that a person-specic consortium of bacteria may be associated with clinically similar periodontal diseases.

Immunological differences and similarities between chronic and aggressive periodontitis

In their review, Ford et al. (7) examine the possibility that there are subtle immunological differences in the innate and adaptive immune responses associated with cases of chronic periodontitis vs. aggressive periodontitis. Toll-like receptors are an important component of innate immunity, as they trigger the release of antimicrobial peptides and proteins when stimulated by pathogen-associated molecular patterns of periodontal microorganisms. Ford et al. (7) discuss some of the intriguing possible differences in Toll-like receptor activation patterns between chronic and aggressive forms of periodontitis. In addition, preliminary data suggest that there are differences between these two forms of periodontitis with respect to the synthesis of b-defensins by host cells. Potential differences in components of the adaptive immune system are also possible. However, these subtle differences do not indicate a different immunopathology for each entity. Overall, the lack of studies of wellcharacterized cases of aggressive periodontitis hinders careful comparisons between the two forms of periodontitis. However, it appears that both diseases have similar immunohistological proles, suggesting similar immunopathological mechanisms.

Human viruses in periodontitis

It has now been established that human viruses are part of the micro-ecosystem of the oral cavity in both chronic and aggressive forms of periodontitis. Evidence from a variety of sources supports a co-infection hypothesis in which the development and progression of periodontal disease is associated with dual infection by certain human viruses (e.g. Epstein Barr virus and cytomegalovirus) in conjunction with an increase in opportunistic pathogenic bacteria residing in the endogenous subgingival microbiota. In the review by Slots (10), important theoretical events associated with this co-infection are summarized. One of the scenarios is that infection with herpes viruses results in a local increase in proinammatory cytokines that subsequently disrupts the homeostatic balance between the resident periodontal microbiota and the host. Members of the subgingival microbiota that thrive under inammatory conditions (e.g. Porphyromonas gingivalis, Tannerella forsythia and Treponema spp.) proliferate and contribute to the development and progression of periodontitis. Also of interest is the hypothesis that primary cytomegalovirus infection during root formation and subsequent reactivation at puberty may be involved in the pathogenesis of localized aggressive periodontitis. This could lead to initial malformation of the attachment apparatus and also account for the clinical feature of minimal plaque that is reported in the initial stages of localized aggressive periodontitis.

Comparison of neutrophil functions in aggressive and chronic periodontitis

The earlier literature dealing with neutrophil function in chronic vs. aggressive forms of periodontitis suggested that patients with localized aggressive periodontitis (i.e. formerly localized juvenile periodontitis) had an inherited trait characterized by lower than normal chemotaxis, phagocytosis and intracellular microbial killing responses when exposed to an intense microbial challenge. Alternatively, it was suggested that the dampened neutrophil responses are an acquired characteristic secondary to persistent exposure to microbial products and inammatory mediators. Ryder (9) summarizes the rationale behind these two points of view, and explains why these altered neutrophil responses were considered important in the progression rates of periodontitis. In addition, he discusses current views regarding modied neutrophil functions associated with different forms of periodontitis. It is currently believed that the constant

Armitage et al.

presence of uncontrolled periodontal infections activates or primes neutrophils to a heightened state of readiness in order to deal more effectively with microbial assaults on the host. When primed neutrophils reach the site of an infection, they rapidly release an array of lytic enzymes that can accelerate local destruction of tissue. As discussed by Ryder (9), it is now believed that some of the differential functions of neutrophils in aggressive forms of periodontitis may be due to a combination of inherited and acquired characteristics. Primed neutrophils are heavily committed to debridement activities at infected sites, and are less likely to display the optimal chemotactic and phagocytic functions that are characteristic of their behavior during earlier stages of infection.

subgingival biolms at regular intervals is absolutely critical for long-term prevention of disease recurrence. It was once incorrectly believed that localized aggressive periodontitis was a degenerative disease that would not respond well to anti-infective treatments. Deas & Mealey (5) compare the responses of chronic and aggressive forms of periodontitis to anti-infective therapy, and conclude that both diseases respond well to this initial management strategy. In addition, all forms of regenerative therapy work well in both diseases. In both cases, long-term success depends on a rigorous program of periodontal maintenance care designed to control the overgrowth of potential pathogens within the biolm.

Genetic and environmental risk factors for chronic and aggressive periodontitis
A risk factor for a disease is any item or condition that is in, or affects, the causal chain for that disease. As all forms of chronic and aggressive periodontitis are infections in a genetically susceptible host, anything in the environment that modies the clinical course or increases this innate susceptibility may be considered a risk factor. In their review, Stabholz et al. (12) discuss the major risk factors for aggressive and chronic forms of periodontitis, and conclude that there are no striking differences in risk factors between these diseases. This is especially true for risk factors associated with generalized aggressive and chronic forms of periodontitis. In addition, both forms of periodontitis have a genetic susceptibility component, although the associated gene polymorphisms may be somewhat different. Genetic risk factors for both diseases clearly exist, but their effects on disease expression are unclear.

Comparative biology of chronic and aggressive periodontitis vs. peri-implantitis

In their review, Heitz-Mayeld & Lang (8) compare the basic features of the most common forms of periodontitis (i.e. chronic and generalized aggressive) with those associated with peri-implantitis. It is clear that periodontitis and peri-implantitis are polymicrobial opportunistic infections caused by the commensal microbiota. In these diseases, tissue destruction around teeth or implants is mediated by similar host inammatory and immunological responses to pathogens residing in the biolms that form on tooth or implant surfaces. Individuals who are susceptible to periodontitis appear to be at a similar risk for developing peri-implantitis. The two conditions have almost identical local and systemic risk factors. In some individuals with peri-implantitis, there is very rapid loss of supporting bone, much faster than that observed even in aggressive cases of periodontitis. The factors that are responsible for this may include variations in toothborne vs. implantassociated microbiota and structural differences in the periodontal tissuetooth interface vs. the implantbone mucosa interface, although the immunopathology appears to be similar.

Response of chronic and aggressive periodontitis to treatment

It has been known for a very long time that antiinfective treatment is very effective in arresting the progression of chronic periodontitis. In addition, after the infection has been controlled, subsequent attempts at regenerating some of the lost periodontal tissues are often successful. Finally, periodic maintenance treatment designed to maximize the effectiveness of the patients oral hygiene and disrupt remove

Unmet research need unambiguous case denitions

All contributors to this volume of Periodontology 2000 expressed concerns about the lack of a consistent and validated literature upon which to base their reviews. There is a major need for the periodontal research

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Chronic vs. aggressive periodontitis

community to develop, and then widely use, valid and acceptable case denitions for each of the three diseases discussed in this volume: Localized aggressive periodontitis Generalized aggressive periodontitis Chronic periodontitis Unambiguous case denitions are critically important if meaningful progress is to be made in understanding the etiology, pathogenesis and management of this complex group of polymicrobial infections. For example, as pointed out by Demmer & Papapanou (6), a young individual with copious amounts of plaque and calculus could have severe generalized chronic periodontitis while a slightly older individual with minimal amounts of plaque and calculus could have generalized aggressive periodontitis. Until unambiguous case denitions are developed, researchers are strongly urged to use stringent case denitions to avoid overlap between the various diseases and to enable valid interpretation of their results, although it is recognized that this may well be at the expense of sample size.

References
1. Armitage GC. Development of a classication system for periodontal diseases and conditions. Ann Periodontol 1999: 4: 16.

2. Armitage GC. Comparison of the microbiological features of chronic and aggressive periodontitis. Periodontol 2000 2010: 53: 7088. 3. Armitage GC, Cullinan MP. Comparison of the clinical features of chronic and aggressive periodontitis. Periodontol 2000 2010: 53: 1227. 4. Bartold PM, Cantley MD, Haynes DR. Mechanisms and control of pathological bone loss in periodontitis. Periodontol 2000 2010: 53: 5569. 5. Deas DE, Mealey BL. Response of chronic and aggressive periodontitis to treatment. Periodontol 2000 2010: 53: 154 166. 6. Demmer RT, Papapanou PN. Epidemiological patterns of chronic and aggressive periodontitis. Periodontol 2000 2010: 53: 2844. 7. Ford PJ, Gamonal J, Seymour GJ. Immunological differences and similarities between chronic periodontitis and aggressive periodontitis. Periodontol 2000 2010: 53: 111 123. 8. Heitz-Mayeld LJA, Lang NP. Comparative biology of chronic and aggressive periodontitis vs. peri-implantitis. Periodontol 2000 2010: 53: 167181. 9. Ryder MI. Comparison of neutrophil functions in aggressive and chronic periodontitis. Periodontol 2000 2010: 53: 124137. 10. Slots J. Human viruses in periodontitis. Periodontol 2000 2010: 53: 89110. 11. Smith M, Seymour GJ, Cullinan MP. Histopathological features of chronic and aggressive periodontitis. Periodontol 2000 2010: 53: 4554. 12. Stabholz A, Soskolne WA, Shapira L. Genetic and environmental risk factors for chronic periodontitis and aggressive periodontitis. Periodontol 2000 2010: 53: 138153.

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