CS4-9)_Periodontitis,Prof.Dr.TolgaTözüm.pdf

Prof. Dr. TOLGA TOZUM YAKINDOĞU ÜNİVERSİTESİ DİŞHEKİMLİĞİ FAKÜLTESİ Learning outcomes: 1-Will be able to explain and clinically distinguish the causes and risk factors of chronic periodontitis with its definition in the 1999 classification. 2- Will be able to explain the microbiology, distribution...

Prof. Dr. TOLGA TOZUM YAKINDOĞU ÜNİVERSİTESİ DİŞHEKİMLİĞİ FAKÜLTESİ Learning outcomes: 1-Will be able to explain and clinically distinguish the causes and risk factors of chronic periodontitis with its definition in the 1999 classification. 2- Will be able to explain the microbiology, distribution, symptoms and progression of chronic periodontitis. 3-Will be able to explain and clinically distinguish the causes and risk factors of generalized and localized aggressive periodontitis with its definition in the 1999 classification. 4- Will be able to describe the microbiology, distribution, severity and symptoms of generalized and localized aggressive periodontitis. 5- Will be able to explain the etiology, risk factors, microbiology, distribution and symptoms of necrotizing periodontitis. 6-Will be able to distinguish the clinical features of chronic periodontitis, aggressive periodontitis and necrotizing periodontitis Aggressive Periodontitis In 2017, a joint world workshop was organized by the European Federation of Periodontology (EFP) and the American Academy of Periodontology (AAP), and periodontal diseases were reclassified.The main reason for the classification change; As a result of clinical, biochemical and microbiological studies conducted in the 2000s, findings proving that chronic and aggressive periodontitis are two different diseases have not emerged. As a result of the discussion sessions held during the workshop, chronic and aggressive periodontitis; It has been accepted that there are no two different diseases that differ from each other in terms of disease causes, pathogenic mechanisms and clinical findings, and they are grouped under the title of periodontitis, and grading and staging were made in periodontitis according to attachment loss, pocket depth, radiographic bone loss and factors that determine the rate of progression. Periodontitis degree Primary Criteria Direct evidence of progressi on Indirect evidence of progressi on Degree modifiers Risk factors Grade A: Slowly progressive Longitudinal data (clinical attachment loss or radiographic bone loss) % bone loss/age No evidence of bone loss over 5 years Grade B: Moderately progressive < 2mm in more than 5 years Grade C: Fast progressing < 0,25 0,25-1,0 >1 Phenotype Large deposits of biofilms seen with low degradation Biofilm compatible destruction ≥ 2mm in more than 5 years Cigarette <10 cigarettes/day More destruction than existing biofilm: Specific clinical patterns suggestive of rapid progression and/or early onset of disease (eg molar-incision pattern, lack of expected response to standard therapy) ≥ 10 cigarettes/day Diabetes HbA1c < 7,0 HbA1c ≥ 7 The part called Aggressive periodontitis (AgP) in the old classification is the part shown in the table in the new classification. There is a rapid progression of the disease, the presence of more than 2 mm attachment loss in more than 5 years was determined as a criterion in the grading, and it can only be observed as a result of the follow-up of this patient. However, the patient's age is young (for example, 20's) and in the presence of very severe bone and attachment loss, it can be assumed that the patient is the rapidly progressive type. AgP is an inflammatory disease associated with many complex causes, which usually starts at an early age and progresses with advanced bone destruction and tooth loss. The progression and severity of the disease are shaped by the interactions between microbiological, immunological, genetic and environmental factors such as race and non-modifiable risk factors such as age, gender, race. Its etiology is not fully known. The disease is divided into 2 subgroups as localized aggressive periodontitis (LAgP) and generalized aggressive periodontitis (GAgP) according to the area of effect, severity and affected teeth. Affected areas or teeth can be grouped as GAgP if less than 30% of all teeth or areas and LagP is more than 30%. Diagnostic Criteria of Localized and Generalized Aggressive Periodontitis Criterion Age of onset Localized Aggressive Periodontitis Circumpubertal Generalized Aggressive Periodontitis Most often <30 years of age, but can also occur in older individuals Serum antibody response against infecting agents Destruction pattern Robust poor Localized attachment loss at incisors and first molars; interproximal attachment loss at two or more permanent teeth, one of which is a first molar, and involvement of two or fewer teeth other than the first molars and incisors Generalized loss of proximal attachment, 1. Diffuse interproximal attachment loss is observed in at least three permanent teeth except molars and incisors. Episodic nature of attachment loss Generalized Aggressive Periodontitis. Generalized aggressive periodontitis (GAP) is the subgroup of periodontal disease that is characterized by the highest severity and extent of disease and also by its large heterogeneity. The diagnosis of GAP encompasses the diseases that were previously classified as generalized juvenile periodontitis and rapidly progressive periodontitis. Two gingival tissue responses can be found in cases of GAP. One involves severe, acutely inflamed tissue that is often proliferating, ulcerated, and fiery red. Bleeding may occur spontaneously or with slight stimulation, and suppuration may be an important feature. This tissue response is thought to occur during the destructive stage, in which attachment and bone are actively lost.In other cases, the gingival tissues may appear pink, free of inflammation, and occasionally with some degree of stippling, although stippling may be absent. However, despite the apparently mild clinical appearance, deep pockets can be demonstrated by probing. In addition Localized Aggressive Periodontitis. Localized aggressive periodontitis (LAP) is usually found in younger individuals than GAP. It is characterized by more pronounced systemic antibody titers against periodontal pathogens than are found in patients with GAP. This could indicate that, in individuals who are susceptible to disease but who also have the ability to enact a robust response against pathogens, the disease might be limited in extent (i.e., LAP). Alternatively, in individuals with a lesser humoral response, the disease would not be limited to the first permanent teeth, and the patient would develop GAP. This would mean that LAP and GAP would merely be phenotypic variations of the same underlying disease. This assumption is backed by several reports that show a sequence of LAP and GAP in the same individuals over time. Epidemiology The question of the prevalence of aggressive periodontitis in different populations is complicated by the fact that the currently used classification2 is relatively young and not easy to apply in epidemiological studies. Therefore, many available studies either (1) report on older, previously used entities of periodontitis that showed early onset or rapid progression but that are not interchangeable with aggressive periodontitis or (2) report only on periodontitis severity and not on diagnosis Case Definition The diagnosis of aggressive periodontitis in epidemiological studies is difficult, because all primary criteria for the disease, rapid progression, systemic health, and familiar aggregation are difficult to reliably assess in the setting of such a study. Both the criteria for systemic health and familiar aggregation would require extensive interviews and thorough verification. The rapid progression of disease can consistently only be documented by following a subject longitudinally and performing at least two subsequent examinations within a reasonable time frame; alternatively, it may be extrapolated from older clinical or radiographic records. These, however, are frequently not available, and they would add extensive bias to the study, because prior providers of oral care were not calibrated. Pathobiology and Risk Factors All forms of periodontitis share certain common pathobiological principles as polymicrobial, biofilm-mediated, chronic inflammatory diseases at the biofilm–gingival interface. For now, we will focus on the biological reasons for the rapid course of destruction in patients with aggressive periodontitis, including looking at research that has investigated the specific properties of aggressive periodontitis in periodontal microbiology, immunology, and genetics. Microbiology Periodontitis is caused by specific microorganisms in a susceptible host. In the subgingival biofilm, up to 700 bacterial species have been identified, some of which have been identified as being causative.The observed higher rate of disease progression in aggressive versus chronic periodontitis could possibly be explained by the presence of specific microorganisms that cause and perpetuate tissue destruction. In addition, the reported familiar aggregation of aggressive periodontitis cases could be also to a certain point explained by an infection or the within-family transmission of specific microorganisms. Therefore, several studies have sought to identify the specific microbial properties of aggressive periodontitis cases. However, when evaluating GAP and LAP as a single entity and solely focusing on a small number of “classic” pathogens, it has been concluded that microbiological infection patterns could not reliably distinguish between this entity and chronic periodontitis cases. However, data from a limited number of studies involving both classic microbiological tools and more recent molecular techniques suggest that there exist differences in microbiological composition between both (1) LAP and both GAP and chronic periodontitis, and (2) CAP and chronic periodontitis Specific Bacteria in Localized Aggressive Periodontitis. In patients with LAP, the situation seems to be different. In these cases, several lines of evidence point to a strong role of specific microorganisms, most notably A. actinomycetemcomitans. For decades, this bacterial species has been associated with LAP, and its presence predicted the development of LAP in two longitudinal studies. Longitudinal studies are of critical importance for the demonstration of a causal relationship, whereas cross-sectional studies can by definition only show correlations that cannot be used to infer causality. In the first longitudinal study, age-, gender- and race-matched juvenile carriers and noncarriers of A. actinomycetemcomitans (serotypes a, b, and c were equally distributed, with no presence of A. actinomycetemcomitans strain JP2) were followed longitudinally. After 1 year of follow-up, 80% of the carriers and only 10% of the noncarriers had developed periodontitis.In the second and larger longitudinal study, the highly leukotoxic A. actinomycetemcomitans (serotype b) strain JP2, which has a 530-bp deletion in its leukotoxin gene operon that leads to a 10- to 20-fold higher production of leukotoxin,29 was found to be directly related to the occurrence of LAP in children in Northern Africa. Specifically, the odds ratio for future attachment loss among carriers of the JP2 strain was 18.0 as compared to 3.0 for carriers of other, non-JP2 strains of A. actinomycetemcomitans. Similar findings can also be found in West African countries such as Ghana. This is in contrast with the eastern parts of Africa, where no studies have reported the presence of JP2 clone strains in patients with periodontitis.A recent study of the occurrence of JP2 clone strains in patients with aggressive periodontitis demonstrated a high incidence of both LAP and GAP, which suggests that both subclasses could be more related than initially thought.In addition, it needs to be noted that LAP is clearly not a monoinfection with A. actinomycetemcomitans; as with all entities involving periodontitis, LAP features a polymicrobial biofilm. In support of this notion is the fact that there are also reports of confirmed cases of LAP that did not involve A. actinomycetemcomitans. Host Response to Bacterial Challenge The inflammatory host response toward pathogens is generally attributed to be responsible for a larger proportion of the tissue destruction in periodontitis than the invading periodontal pathogens themselves. The rapid progression of aggressive periodontitis implies that—in addition to the aforementioned composition of the subgingival microbiological flora—specific properties of this inflammatory response render the individuals with aggressive periodontitis both more susceptible to disease and more prone to lose more attachment in a shorter amount of time. Host Response Specific to Aggressive Periodontitis. With regard to GAP, a recent review concluded that “there appears to be no difference between aggressive and chronic periodontitis in terms of their histopathology and immunopathology.”Still, it has to be acknowledged that this could mean that there exist no differences or, rather, that “the differences between both disease entities only reflect variations in the degree of severity of susceptibility rather than actual different immune-pathologies.”Most recently, the stronger activation of natural killer cells and natural killer T cells in patients with aggressive periodontitis was suggested to be causative for the more pronounced tissue destruction that has been observed in these patients. Abnormalities in Localized Aggressive Periodonti-tis. Earlier work suggested that individuals with LAP were characterized by an inherited defect of neutrophil function that led to a dampened immune response against the microflora inhabiting the periodontal pocket. Specifically, when challenged with periodontal pathogens, the LAP neutrophils were reported to show impaired chemotaxis, phagocytosis, and killing of bacteria. Alternatively, it was also hypothesized that these impaired defense properties were in fact acquired defects caused by prolonged exposure to an inflammatory microenvironment. Today, the understanding of neutrophil biology is that neutrophils arriving at a site with uncontrolled periodontal inflammation are primed to attack the invading pathogens by releasing lytic enzymes. These enzymes may, on the other hand, accelerate tissue destruction. It is hypothesized that the observed dampened neutrophil function in deep aggressive periodontitis lesions is due to the heavy commitment of primed neutrophils to debridement so that less potency remains for chemotaxis and defense. Genetics: Family Studies. A familiar aggregation of aggressive periodontitis cases is a secondary feature of the disease entity; it is often (but not always) found with aggressive periodontitis. To assess the familiar component of the disease, twin studies were performed, and these demonstrated a strong genetic component with a likely autosomal-dominant inheritance pattern and a 70% (African-Americans) to 73% (Caucasians) penetrance.Genetics: Polymorphisms. Accordingly, there has been extensive work to determine the inherent genetic traits that underlie this familiar aggregation. Environmental Factors That Affect Susceptibility. The amount and duration of smoking are important variables that can influence the extent of destruction seen in young adults.Patients with GAP who smoke have more affected teeth and more loss of clinical attachment than nonsmoking patients with GAP.However, smoking may not have the same impact on attachment levels in younger patients with LAP. Current Developments. On the basis of the aforementioned still incomplete current understanding of the specific microbiological, immunological, and genetic properties of the clinical symptom based periodontitis entities aggressive and chronic periodontitis, research now focuses on the assessment whether these entities are in fact sufficiently distinct with respect to their underlying pathobiology to form etiology-based clinical classes. For these analyses, novel, unbiased, high-throughput methodologies such as microarrays and next-generation sequencing are employed. Diagnosis Assessment of Clinical Presentation The most reliable diagnostic marker for periodontitis is periodontal probing. However, this technique merely assesses a loss of attachment; it does not classify subcategories of periodontal disease. The diagnosis of aggressive periodontitis in the clinic is therefore made by jointly assessing the primary and secondary features of aggressive periodontitis, as described previously. As a result of the small but significant prevalence of this severecategory of periodontal disease, it is recommended to also routinelyscreen for the presence of attachment loss in younger patients with the use of Periodontal Screening and Recording or the Periodontal Screening Index every year. In patients with significant findings, a more thorough clinical assessment that includes the evaluation of periodontal probing depth and attachment loss at six sites per tooth should be performed. Assessment of Radiographic Presentation Radiographic evidence of periodontal bone loss is a very specific but not very sensitive diagnostic sign of periodontitis.It has been suggested to screen for bone loss in younger children and adolescents with the use of the bite-wing radiographs that are regularly obtained for the early detection of dental caries; in this population with erupting permanent teeth, periodontal probing can be difficult. A distance of 2 mm between the cementoenamel junction and the alveolar bone crest in these patients could be a sign of periodontitis and may warrant a more thorough examination.70 Assessment of Microbiological Burden There exists a wealth of commercially available tests for sampling the subgingival microbiota. These tests most often assess the presence and estimate the relative numbers of 3 to 20 prominent periodontal pathogens. However, the sensitivity and specificity of these tests is disputed. In addition, in patients with aggressive periodontitis, the test results will likely not change standard treatment protocols, which most often include the prescription of systemic antibiotics as adjuncts to anti-infective therapy. Therefore, some authors suggest that microbial testing can be omitted. Assessment of Genetic Features Because recent large-scale and well-controlled studies could not replicate earlier reports from smaller collectives of an association of candidate genes (e.g., interleukin-1) with aggressive periodontitis, it seems unwarranted at the present time to test putative aggressive periodontitis patients for the presence of DNA polymorphisms or other genetic markers. Assessment of Host Defense In a suspect case of rapidly progressing aggressive periodontitis, one may consider the use of one of the commercially available tests for markers of ongoing periodontal inflammation and tissue breakdown in either gingival crevicular fluid or saliva (e.g., matrix metalloproteinase-8) or other areas. Still, none of the available tests to date can reliably discriminate aggressive periodontitis from other conditions, and thus the utility of these tests to assess ongoing tissue breakdown is disputed. Furthermore, their value (if any) lies primarily in screening individuals for the recurrence of disease during the maintenance phase rather than providing an initial diagnosis. Therefore, the use of these tests for the diagnosis of aggressive periodontitis is not recommended at present. Therapeutic Considerations for Patients With Aggressive Periodontitis Considerations for the Anti-infective Therapy of Aggressive Periodontitis Anti-infective therapy in patients with aggressive periodontitis seems to benefit strongly from the adjunctive use of systemic antibiotics. Considerations for the Surgical Therapy of Aggressive Periodontitis In general, individuals with aggressive periodontitis, especially LAP, have to undergo surgical therapy more often than the average patient with periodontitis. This is due to the following: (1) the often much more pronounced loss of attachment with deep periodontal pockets that are challenging to instrument4,42; and (2) the high prevalence of vertical defects, most notably in patients with LAP, that need to be resolved.Considerations for the Supportive Periodontal Therapy of Patients With Aggressive PeriodontitisIt is the current view that patients with aggressive periodontitis suffer from a combination of an especially virulent microbiological burden in combination with alterations in their host defense that render them more prone to rapid attachment loss, even in the absence of seemingly “adequate” amounts of etiological factors. This suggests that, during the maintenance phase, utmost care needs to be taken to optimize self-performed oral hygiene to minimize the amount of plaque that could eventually lead to a new and rapid loss of attachment. Therefore, many clinicians recommend performing supportive periodontal therapy, including the regular assessments of periodontal parameters, at least every 3 months. This should even be the schedule for patients who show particularly high levels of oral hygiene proficiency, and it should be independent of the Periodontal Risk Assessment tool, which seems to be of limited use in patients with aggressive periodontitis. Considerations for Oral Rehabilitation and Implant Therapy in Patients With Aggressive Periodontitis Dental implants today allow for the routine and predictable func- tional and aesthetic replacement of lost teeth. Still, there are concerns about the incidence of peri-implantitis; this is an inflammatory condition of dental implants that has parallels with periodontal disease and for which no defined, predictable treatment protocols exist to date. Peri-implantitis risk is linked to a history of periodontal disease in the individual with dental implants. There exist limited data that show an even stronger risk for the development of the disease among patients with aggressive periodontitis as compared with patients with chronic periodontitis or periodontally healthy controls. Chronic Periodontitis Chronic periodontitis is the most prevalent form of periodontitis, and it generally demonstrates the characteristics of a slowly progressing inflammatory disease. However, systemic and environmental factors (e.g., diabetes mellitus, smoking) may modify the host’s immune response to the dental biofilm so that periodontal destruction becomes more progressive. Although chronic periodontitis is most frequently observed in adults, it can occur in children and adolescents in response to chronic plaque and calculus accumulation. Chronic periodontitis has been defined as “an infectious disease resulting in inflammation within the supporting tissues of the teeth, progressive attachment loss, and bone loss.” This definition out-lines the major clinical and etiologic characteristics of the disease: (1) microbial biofilm formation (dental plaque); (2) periodontal inflammation (e.g., gingival swelling, bleeding on probing); and (3) attachment as well as alveolar bone loss. In addition to the local immune response caused by the dental biofilm, periodontitis may also be associated with a number of systemic disorders and defined syndromes. In most cases, patients with systemic diseases that lead to impaired host immunity may also show periodontal destruction. Therefore, periodontitis is a disease that is not only limited to the area of the oral cavity; it is also associated with severe systemic diseases (e.g., cardiovascular disorders, diabetes mellitus). Clinical Features General Characteristics Characteristic clinical findings in patients with untreated chronic periodontitis include the following: • Supragingival and subgingival plaque and calculus • Gingival swelling, redness, and loss of gingival stippling • Altered gingival margins (e.g., rolled, flattened, cratered papillae, recessions) • Pocket formation • Bleeding on probing • Attachment loss (angular or horizontally) • Bone loss • Root furcation involvement (exposure) • Increased tooth mobility • Change in tooth position • Tooth loss Chronic periodontitis can be clinically revealed with periodontal screening and recording, which results in a periodontal screening index rating. The condition is diagnosed via the assessment of the clinical attachment level and the detection of inflammatory changes in the marginal gingiva.Measurements of periodontal pocket depth in combination with the location of the marginal gingiva allow for conclusions to be drawn regarding the loss of clinical attachment. Disease Distribution Chronic periodontitis is considered a site-specific disease. Local inflammation, pocket formation, attachment loss, and bone loss are the consequences of direct exposure to the subgingival plaque (biofilm). As a result of this local effect, pocket formation and attachment as well as bone loss may occur on one surface of a tooth, whereas other surfaces maintain normal attachment levels. As a result of the site-specific nature, the number of teeth with clinical attachment loss classifies chronic periodontitis into the following types: • Localized chronic periodontitis: less than 30% of the sites show attachment and bone loss • Generalized chronic periodontitis: 30% or more of the sites show attachment and bone loss Disease Severity The severity of periodontal destruction that occurs as a result of chronic periodontitis is generally considered a function of time in combination with systemic disorders that impair or enhance host immune responses. With increasing age, attachment loss and bone loss become more prevalent and more severe as a result of an accumulation of destruction. Disease severity may be described as mild, moderate, or severe: • Mild chronic periodontitis: when no more than 1 mm to 2 mm of clinical attachment loss has occurred • Moderate chronic periodontitis: when 3 mm to 4 mm of clinical attachment loss has occurred • Severe periodontitis: when 5 mm or more of clinical attach- ment loss has occurred Symptoms Chronic periodontitis is commonly a slowly progressive disease that does not cause the affected individual to feel pain. Therefore, most patients are unaware that they have developed a chronic disease that is also associated with other systemic diseases (e.g.,cardiovascular disease). For the majority of the patients, gingival bleeding during oral hygiene procedures or eating may be the first self-reported sign of disease occurrence. As a result of gingival recession, patients may notice black triangles between the teeth or tooth sensibility in response to temperature changes Disease Progression Patients appear to have the same susceptibility to plaque induced chronic periodontitis throughout their lives. The rate of disease progression is usually slow, but it may be modified by systemic, environmental, and behavioral factors. The onset of chronic periodontitis can occur at any time, and the first signs may be detected during adolescence in the presence of chronic plaque and calculus accumulation. Because of its slow rate of progression, however, chronic periodontitis usually becomes clinically significant when a patient reaches his or her mid-30s or later. Chronic periodontitis does not progress at an equal rate in all affected sites throughout the mouth. Some involved areas may remain static for long periods,whereas others may progress more rapidly. More rapidly progressive lesions occur most frequently in interproximal areas, and they may also be associated with areas of greater plaque accumulation and inaccessibility to plaque control measures (e.g., furcation areas, overhanging margins of restorations, sites of malposed teeth, areas of food impaction). Prevalence Chronic periodontitis increases in prevalence and severity with age, and it generally affects both genders equally. Periodontitis is an age-associated (not an age-related) disease. Nonetheless, the prevalence of periodontitis increases with age so that 40% of patients who are 50 years old or older and almost 50% of patients who are 65 years old or older show moderate periodontal destruction. The prevalence of severe forms of periodontitis also increases with age. Up to 30% of patients develop severe periodontitis by the time they are 40 years old or older. Generally, 50% of the human population experiences at least one form of periodontal disease Risk Factors for Disease A number of different factors influence the etiopathology of chronic periodontitis. The composition of the oral microflora is a major etiologic factor that leads to periodontal destruction. In this context, the extent of the periodontal destruction depends on the host’s immune competence as well as genetic predispositions that influence individual susceptibility to disease. In addition, both systemic diseases and environmental factors interfere with the development and progression of chronic periodontitis. Microbiological Aspects Plaque accumulation on tooth and gingival surfaces at the dento gingival junction is considered the primary initiating agent in the etiology of gingivitis and chronic periodontitis. Attachment and bone loss are associated with an increase in the proportion of gram-negative organisms in the subgingival biofilm, with specific increases in organisms that are known to be exceptionally pathogenic and virulent. Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola—otherwise known as the “red complex”—are frequently associated with ongoing attachment and bone loss in patients with chronic periodontitis. The development and progression of chronic periodontitis may not depend on the presence of one specific bacterium or bacterial complex alone. It is assumed that chronic periodontitis is the result of a multispecies infection with a number of different bacteria that influence the pro-inflammatory immune response of the host. Local Factors Plaque accumulation and biofilm development are the primary causes of periodontal inflammation and destruction. Therefore,factors that facilitate plaque accumulation or that prevent plaque removal by oral hygiene procedures can be detrimental to the patient. Plaque-retentive factors are important for the development and progression of chronic periodontitis, because they retain microorganisms in proximity to the periodontal tissues, thereby providing an ecologic niche for biofilm maturation. Calculus is considered the most important plaque-retentive factor as a result of its ability to retain and harbor plaque bacteria on its rough surface as well as inside. As a consequence, calculus removal is essential for the maintenance of a healthy periodontium. In addition, tooth morphology may influence plaque retention. Roots may show grooves or concavities, and, in some instances, enamel projections on the surface or the furcation entrances. These morphologic variations may facilitate plaque retention, subgingival calculus formation, and disease progression.In addition, subgingival and overhanging margins of restorations, carious lesions that extend subgingivally, and furcations exposed by loss of bone promote plaque retention. Systemic Factors Chronic periodontitis is a complex disease that may not only be limited to the infection of local sites. In several instances, periodontitis is also associated with other systemic disorders, such as Haim– Munk syndrome, Papillon–Lefèvre syndrome, Ehlers–Danlos syndrome, Kindlers syndrome, and Cohen syndrome. Patients with diseases that impair the host immune response (e.g., human immunodeficiency virus, acquired immunodeficiency syndrome) may also show periodontal destruction.For diabetes mellitus and periodontitis, it is known that there is an interaction during which both diseases mutually correlate with each other. Patients with diabetes mellitus exhibit a higher risk for the development of periodontitis, and periodontal infection and inflammation may negatively interfere with the glycemic control of the diabetic patient. A number of studies showed that the prevalence, severity, and prognosis of periodontitis are associated with the incidence of diabetes mellitus. It was found that the average pocket depth as well as the clinical attachment loss was increased in patients with diabetes mellitus Immunologic Factors Chronic periodontitis is a disease that is induced by bacteria organized in the dental biofilm. However, the onset, progression, and severity of the disease depend on the individual host’s immune response. Patients may show alterations in their peripherial monocytes, which are related to the reduced reactivity of lymphocytes or an enhanced B-cell response. B-cells, macrophages, periodontal ligament cells, gingival fibroblasts, and epithelial cells synthesize pro-inflammatory mediators (e.g., interleukin-1β, interleukin-6, interleukin-8, prostaglandin E2, tumor necrosis factor-α) that modify innate and adaptive immune responses at periodontal site Pro-inflammatory mediators regulate the synthesis and secretion of, for example, matrix metalloproteinases and receptor activator of nuclear factor-κβ ligand (RANKL). In periodontal lesions, matrix metalloproteinases contribute to soft- and hard-tissue degradation during active inflammatory reactions.RANKL binds to its receptor activator of nuclear factor-κβ on the cell surface of premature osteoclasts, thereby initiating osteoclast differentiation that leads to the degradation of alveolar bone. Genetic Factors Periodontitis is considered to be a multifactorial disease that is influenced by local, systemic, and immunologic factors, as described previously. Each factor is in turn directly related to individual genetic conditions. Genetic variations such as single nucleotide polymorphisms (SNPs) and genetic copy number variations may directly influence innate and adaptive immune responses as well as the structure of periodontal tissues. Periodontal destruction has been found among family members and across different generations within a family, thereby suggesting a genetic basis for the susceptibility to periodontal disease. In a number of studies, the prevalence of aggressive and chronic periodontitis has been investigated in families with a history of one or more family members with periodontitis. Environmental and Behavioral Factors In addition to microbial, immunologic, and genetic factors, the development and progression of chronic periodontitis is further influenced by environmental and behavioral factors, such as smoking and psychological stress. Smoking is a major risk factor for the development and progression of generalized chronic periodontitis. Periodontitis is influenced by smoking in a dose dependent manner. The intake of more than 10 cigarettes per day tremendously increases the risk of disease progression as compared with non-smokers and former smokers.As compared with non-smokers, the following features are found in smokers: • Increased periodontal pocket depth of more than 3 mm • Increased attachment loss • More recessions • Increased loss of alveolar bone • Increased tooth loss • Fewer signs of gingivitis (e.g., less bleeding with probing) • Greater incidence of furcation involvement As a result of the consumption of tobacco, reactive oxygen (i.e., radicals) is released that chemically irritates periodontal tissues via DNA damage, the lipid peroxidation of cell membranes, the damage of endothelial cells, and the induction of smooth muscle cell growth. NECROTIZING ULCERATIVE PERIODONTITIS (NUP) Necrotizing Ulcerative Periodontitis (NUP) may be an extension of necrotizing ulcerative gingivitis (NUG) into the periodontal structures that leads to periodontal attachment and bone loss. Alternatively, NUP and NUG may be different diseases. NUG and NUP can be proved or disproved, it has been suggested that NUG and NUP be classified together under the broader category of necrotizing periodontal diseases, although with differing levels of severity. The term necrotizing ulcerative gingivoperiodontitis was given in 1986. The term necrotizing ulcerative periodontitis was first adopted at the 1989 World Workshop in Clinical Periodontics. In 1999, the subclassifications of NUG and NUP were included as separate diagnoses under the broader classification of “necrotizing ulcerative periodontal diseases.Similar to NUG, clinical cases of NUP are defined by necrosis and ulceration of the coronal portion of the interdental papillae and gingival margin, with a painful, bright-red marginal gingiva that bleeds easily. The distinguishing feature of NUP is the destructive progression of the disease, which includes periodontal attachment and bone loss. Deep interdental osseous craters typify periodontal lesions of NUP. However, “conventional” periodontal pockets with deep probing depth are not found, because the ulcerative and necrotizing nature of the gingival lesion destroys the marginal epithelium and connective tissue, thereby resulting in gingival recession. Periodontal pockets are formed because the junctional epithelial cells remain viable and can therefore migrate apically to cover areas of lost connective-tissue attachment. The necrosis of the junctional epithelium in patients with NUG and NUP creates an ulcer that prevents this epithelial migration, and a pocket cannot form. Advanced lesions of NUP lead to severe bone loss, tooth mobility, and ultimately tooth loss. In addition to these manifestations, as previously mentioned, patients with NUP may present with oral malodor, fever, malaise, or lymphadenopathy. In a study involving the use of transmission electron microscopy and scanning electron microscopy of the microbial plaque overlying the necrotic gingival papillae, Cobb and colleagues demonstrated striking histologic similarities between NUP in HIV-positive patients and previous descriptions of NUG in HIV-negative patients. Microscopic examination revealed a surface biofilm composed of a mixed microbial flora with different morphotypes and a subsurface flora with dense aggregations of spirochetes (i.e., the bacterial zone). Gingival and periodontal lesions with distinctive features are frequently found in patients with HIV infection and AIDS. Many of these lesions are atypical manifestations of inflammatory periodontal diseases that arise during the course of HIV infection and as a result of the patient’s concomitant immunocompromised state. Linear gingival erythema, NUG, and NUP are the most common HIV-associated periodontal conditions reported in the literature.NUP lesions found in patients with HIV or AIDS can present with features similar to those seen in HIV-negative patients. Alternatively, NUP lesions in patients with HIV or AIDS can be much more destructive and frequently result in complications that are extremely rare among patients without HIV or AIDS. For example, periodontal attachment and bone loss associated with NUP in an HIV-positive patient may be extremely rapid. The etiology of NUP has not been determined, although a mixed fusiform–spirochete bacterial flora appears to play a key role. Numerous predisposing factors have been attributed to NUG, including poor oral hygiene, preexisting periodontal disease, smoking, viral infections,immunocompromised status, psychosocial stress, and malnutrition. NUG and NUP are more prevalent and more severe among patients with HIV. These patients require urgent treatment, because untreated lesions can progress rapidly; within a few days, severe bone loss around affected teeth can be seen. Murray and colleagues reported that cases of NUP in HIV-positive patients demonstrated significantly greater numbers of the opportunistic fungus Candida albicans and a higher prevalence of Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium nucleatum, and Campylobacter species as compared with HIV-negative controls. In addition, they reported a low or variable level of spirochetes, which is inconsistent with the flora associated with NUG. 1-Newman M, Takei H, Klokkevold P, Carranza F. Newman and Carranza (2019); Clinical Periodontology, 13th Ed., Elsevier.