Aggressive periodontitis

Presented by : Dr. Alka kaushik P.G. STUDENT

1. Introduction 2.Classification and clinical syndrome 3. Localized aggressive periodontitis 4. Generalized aggressive periodontitis 5. Epidemiology - primary and permanent dentition 6. Risk factors for periodontitis 7. Etiology and pathogenesis - Microbiological factor - Immunological factors - genetic factor - Environmental factor - Current concept 8. Diagnosis 9.Treatment

1999 international classification workshop

periodontitis

Chronic

Aggressive

Necrotising

Systemic disease manifestation

What is Aggressive periodontitis???

CLASSIFICATION AND CLINICAL SYNDROMES PRIMARY FEATURES (lang et al)

Non contributory systemic disease

Rapid attachment loss and bone destruction

Familial aggregation of cases

SECONDARY FEATURES
Hyperresponsive macrophage phenotype, including elevated PGE2 and IL1 in response to bacterial endotoxins

microbial deposit inconsistent with the severity

Phagocyte abnormality

Elevated proportions of AaC, P.gingivalis

Progression of attachment loss and bone loss may be self arresting

Tonetti & Mombelli 1999, Lang et al 1999).

Localised aggressive periodontitis

Generalised aggressive periodontitis

Mombelli et al 2002

Secure aggressive periodontitis

Insecure aggressive periodontitis

Uncertain aggressive periodontitis

In 1923, Gottlieb diffuse atrophy of the alveolar bone.

In 1942 Orban and Weinmann

periodontosis
stages -1,2 and 3 HISTORICAL BACKGROUND

In 1928, Gottlieb deep cementopathia and hypothesized that this was a disease of eruption

In 1940 Thoma and Goldman paradontosis

In 1938, Wannemacher parodontitis marginalis progressive.

In 1952 Glickman extreme variant of destructive processes In 1989 the world workshop -of early-onset periodontitis

Historical background

HISTORICAL BACKGROUND

1966 the world workshop degenerative entity was unsubstantiate d

In 1971, Baer disease of the periodontium occurring in an otherwise healthy adolescent

juvenile periodontitis was introduced by Chaput and colleagues in 1967 and by Butler in 1969.

Localized aggressive periodontitis

Clinical features

Localised aggressive periodontitis.

Other clinical features

Lack of clinical inflammation despite the presence of periodontal pocket

Advanced bone loss

Minimal amount of Plaqueelevated level of Aac and in some case Porphyromonas gingivalis. . Distolabial migration of maxillary incisor with concomitant diastema formation Increased mobility

Radiographic features

Possible reasons for the limitation of periodontal destruction to certain teeth

After initial colonization of the first permanent teeth to erupt , AAC evades the host defense
Colonization of bacteria antagonistic to A.ac A.Actinomycetamcomitans may loose its leukotoxin

producing ability
A defect in cementum formation

Prevalence and distribution by age SS

The prevalence of LAP in geographically diverse

adolescent population is estimated less than 1%. Most report suggest a low prevalence about 0.2%

Generalized aggressive periodontitis

Clinical features person under 30 years of age, but patient may be older Generalized interproximal attachment loss affecting at least three permanent teeth other than first molar and incisors Pronounced episodic nature of destruction of attachment loss and alveolar bone Poor serum antibody response to infecting agent

TISSUE RESPONSE TWO TYPES

Severe acutely inflamed tissue

Gingival tissue may appear pink, free of inflammation

Some patients systemic manifestations,

such as weight loss. mental depression, and general malaise.

Age and sex distribution

puberty and 30 years of age
Both males and females Some studies shows a predilection for female patient

particularly in the youngest age group whereas other report no male female differences in incidence. Among blacks, males are affected more than females.

Radiographic findings
minimal number of teeth, to

advanced bone loss Vertical loss of alveolar bone Arc shaped loss of alveolar bone

Epidemiology
Epidemiological studies relate aggressive periodontitis to

early onset periodontitis.

Aggressive form of periodontal disease are detectable in all

age and ethnic groups ( Papapanou 1996)

wide variation in the prevalence, with some studies

showing up to 51.5 % affected individuals. These differences are probably due to the difference in the employed epidemiological methodologies definition of early onset periodontitis

PRIMARY DENTITION
Little evidence is available few studies marginal alveolar bone loss

primary dentition of 5-11 yr old (frequency of 0.9-4.5%.)

periodontitis effecting the primary dentition does not

necessarily mean presence of an aggravated form of periodontitis, abundance of local factors( plaque and calculus).

but may indicate a chronic form of disease with relative tooth exfoliation early in life are usually interpreted as

periodontal manifestation of systemic disease such as leukocyte adhesion deficiency.

Permanent dentition
In permanent dentition between age group between 3-20

year prevalence of periodontitis is less than 1%.however it differs among different population: In US school children 5-17 yrs prevalence is 0.2% for whites, 2.6% for blacks ( Loe & Brown) Longitudinal studies have shown that young age subjects with signs of destructive periodontitis are prone to further deterioration. -more pronounced - initially affected sites, patient diagnosed with LAP and low socioeconomic states. -involves both an increase in extent and increase in severity of lesion.( Clerehugh et al 1990, Lissau et al 1990, Albander et al 1991a,b, 1993, Aass et al 1994)

Risk factors
Microbiological Immunological Genetic Environmental Current concept

Bacterial etiology
AAc
Campylobactor rectus
Capnocytophaga species Eikenella coorrodens Prevotella intermedia

Bacterial etiology

Eikenella corrodens

Prevotella intermedia

campylobactor

capnocytophaga

AAC

bacterial etiology. Bacterial damage to the periodontium

Bacteria causes destruction the

marginal periodontium via two related mechanism 1. Direct action of the microorganism or their products on the host tissue 2. As a result of their eliciting tissue damaging inflammatory response

Host defense
Intact epithelial barrier Salivary components Sulcular fluid components local antibody production high level of tissue turnover presence of normal flora or

beneficial species emigrating PMNs and other leukocytes

bacterial etiology Why Aac is considered as primary pathogen???

Tonetti & Mombelli
1. found in high frequency (LAP LESION) 2. Sites with evidence of disease progression of often show elevated level of Aac 3. significantly elevated serum antibody titers to Aac 4. correlation between reduction in the subgingival load of Aac during treatment and a successful clinical response. 5. Aac produces a number of virulence factor

Socransky and Haffajee- LINK IS BASED ON

Association studies linking the organism to the

disease Demonstration of the virulence factor including leucotoxin Finding of immune response correlation between treatment outcome and level of AAC

Leucotoxin

Endotoxin

Virulence factors

Collagenase

bacteriocin

Host response to bacterial pathogens

local and systemic host response Local inflammatory response - recruitment of leucocytes

B cell and antibody producing plasma cell (Lijenberg & Lindhe 1980)
Type of Plasma cell.( Mackler et al 1977,1978) Depressed T-helper to T- suppressor ratio in blood

High level o f PGE2, IL-1 and IL-1 in AgP patients

Host response to bacterial pathogen.

Substantial titers of AgP associated antibodies and cleaved complement fragment in GCF

LAP

High titers and high avidity of AAC specific IgG2

In GAP patients antibody response to P.gingivalis

PMN defect may be inherited

PMNs present decreased migration and antibacterial function

PMNs abnormality -result of a hyper -inflammatory state - pro-inflammatory cytokines (Shapira et al 1994, Agarwal et al 1996).

Genetic factor
prevalence of AgP is high among certain famlies whearas percentage of affected sibling may reach 40-50%. pattern of disease transmission is consistent with mendelian inheritace of a gene of major effect. This means that observed familial pattern can be partly accounted for by one or more genes that could predispose individual to develop AgP.

Genetic factors..
Segregation analysis - Autosomal dominant It is possible to find other mode of inheritance in different

population. Linkage analysis - chromosomal location of a gene of major effect for a trait. Several loci have been proposed as genes conferring increased susceptibility to AgP. these genes are associated with neutrophils function and with the host ability to effectively deal with the LPS exposure.

Genetic factors..
Beside gene of major effect other gene may act as

modifying gene The ability to control high titer of specific antibodies is race dependent and probably protective. Allelic variation in the Fc receptor for IgG2 immunoglobulin have also been suggested to play role in suboptimal handling of Aac infection. PMNs expressing the R131allotype of FcRIIa( Fc receptor containing an arginine instead of histidine at amino acid 131) shows decreased phagocytosis of A.a.

Segregation analysis
Aggressive periodontitis aggregates in families. suggests but does not prove the disease has a genetic basis

because .

mode of inheritance for localized and generalized aggressive

periodontitis are considered as variant of the same disorder.

This theory is supported by the observation that both forms occur

in the same family, the probability of two rare disease occurring in same family is exceedingly small.

Various forms of aggressive periodontitis (e.g. prepubertal and

juvenile periodontitis) have been observed in the same family and found to occur sequentially in the same individual. These findings suggest there are common genetic risk factor for the subforms of AP.

BOTH FORM HAVE A SAME GENETIC BASIS

Segregation analysis..
Many reports in the literature describing families with

multiple effected individuals Pattern of disease in these families lead to investigation Both dominant and recessive mode of inheritance for AP disease

 Melnick et al proposed X-linked inheritance because Father to son transmission

Finnish population - Autosomal recessive (parents of

probands were not consistently unaffected) U.S. study conducted African-american and Caucasian families - Autosomal dominant

Despite inconsistent conclusion regarding their mode of inheritance, segregation analysis consistently have supported the role of major gene in the etiology of AP.

Schenkein

MODEL OF INHERITANCE

to distinguish b/n etiology of LAP AND GAP

He theorized that AP disease and IgG2 responsiveness to bacterial lipopolysaccharide segregate independently as dominant and codominant traits, respectively. The subjects with one AP disease allele and two copies of high IgG-2 response allele -localized disease. one AP disease allele and only one copy of the IgG2allele more widespread disease (because the IgG2 response to lipopolysaccharide would be less robust)

Linkage studies
Linkage between the AgP and a specific chromosomal

region. (Boughmen et al first reported) Autosomal dominant form of AgP & dentinogenesis imperfecta (DGI). AgP disease gene - long arm of chromosome 4 near the gene for DGI. Aggressive periodontitis does not typically co-segregate with DGI, however, and it is unlikely an important AP disease gene reside within this chromosomal region in the more general population.

Association studies
Role of HLA
More than 40 autoimmune diseases are associated with

HLA antigen. Two antigens HLA A9 and HLA B15. The risk of disease in subjects wit HLA A-9 and B-15 is about 1.5 to 3.5 times greater . HLA-A2 antigens - less prevalent in AgP patients (may be protective.

ASSOCIATION STUDIES
Class II DR4 antigen - association with type I diabetes

mellitus. DR4 antigen - is more prevalent in AgP patients in control, (Katz et al ). Role of IL-1 Pleiotropic; stimulate bone resorption , inhibit collagen synthesis, and up-regulate matrix metalloproteinase activity and prostaglandin synthesis. Polymorphism in the vitamin-D receptor and IL-1 receptor antagonist genes and mutation in the N-formyl-1-methionyl-1-leucyl-1phenylalanine receptor gene have been associated with aggressive periodontal disease.

Association with genetic and inherited conditions

The search for periodontitis suceptiblity alleles is

complicated because 1) etiologic heterogeneity 2) genetic heterogeneity

Genetic and inherited disorder associated with aggressive periodontitis

DISORDER
Leucocyte adhesion deficiency type I Leucocyte adhesion deficiency type II

PROTEIN OR TISSUE DEFCET

CD 18 (-2 inegrin chain of LFA

molecule)

CD 15(neutrophils ligand for E and P-

selectin); inborn error in fucose metabolism

Actalasia
Chronic and cyclic neutropenia Chediak Higashi syndrome

Catalase enzyme
Unknown abnormal transport of vesicle to and

from neutrophils lysosomes caused by mutation in the lysosome trafficking regulator gene.
unknown for EDS type VIII

Ehler Danlos syndrome

Type III collagen for EDS type IV,

continue
DISORDER
Papillon lefevre syndrome Hypophosphatasia Trisomy 21 Prepubertal-

PROTEIN/TISSUE DEFECT
Catepsin C dipeptidyl

aminopeptidase I
Tissue nonspecific alkaline

phosphatase
Multiple; critical trisomic region

at least 5 Mb long

periodontitis(non syndromic)
Kindler syndrome

Cathepsin C

Defect in actin- extracellular

matrix linkage caused by loss of function mutation in KIND-1

Immunologic factors
Role of immune defect - pathogenesis of AgP Role of HLA - HLA A9 and B15 antigens

patients with AgP display functional defect of PMNs,

Monocytes or both. can impair either the chemo tactic attraction / phagocytosis AAC as well as some strains of most putative periodontal pathogens are resistant to serum mediated killing mechanisms.

Immune defect..
Deficiency in GP110

dysfunctional neutrophils - decreased expression of G- protein

couple receptors (Approx.75% of patients )

Pan receptor defect/global membrane receptor defect

decrease in the chemotactic response to several chemotactic agent

trans-endothelial migration, trans-epithelial migration, chemo taxis, secretion and priming can be effected

Immunological factor
The molecular basis for the receptor defect is postulated to be inherited as an intrinsic cellular defect

or a modulation of neutrophils receptor expression by elevated level of proinflammatory cytokines including IL-1 and TNF
LAP patients who do not show G-protein couple receptor deficiency has the same clinical feature as with the neutrophils defect. This suggests that the G-protein couple receptor deficiency is sufficient but not essentially for LAP, and other alteration of the host bacterial interaction may yield a similar clinical outcome

Immunological factor.
In LAP collagenase (in tissues & GCF) MMP-1 TIMP-1 Elevated level of antibodies to AAC ( IgG2)

Antibody & complement

Chronic periodontitis, collagenase MMP-8. b/c of altered neutrophils function .

opsonization & phagocytosis. .

immunological factor.
variant of the Fc receptor on neutrophils ( R131 allele of FcRII-)
does not efficiently bind IgG2

B/C of less efficient binding , an antibody response more vigorous than normal is necessary to control the AAC infection in LAP,

supported by the observation that patient with an elevated antibody response have significantly less loss of attachment.

In comparison, individual with generalized early onset periodontitis do not develop a strong antibody response which support the hypothesis that antibodies function to limit the disease process.

Possible destructive mechanism

AAC can produce substance that can kill PMNs and monocytes. Inhibition of PMNs chemotaxis produce a fibroblast inhibiting factor that impairs the defense mechanism.

Endotoxin from AAC can induce Schwartzman reaction, macrophage toxicity, platelet aggregation, complement activation and bone resorption

Polyclonal Blymphocytes activation by periodontal bacteria may result in production of antibodies unrelated to the activating agent.

By Lindhe and slots

Environmental factors
smoker patients

IgG2
antibody level against A.a. significantly depressed.

Ciggrete smoking risk factor for GAP patients (Schenkein et al 1995).

More affected teeth and greater mean level of attachment loss.

Current concepts
MICROBIAL EXPOSURE & INFECTION ,AAC NORMAL LAP CIGGRETTE SMOKING P.GINGIVALIS & OTHER BACTERIA GAP

GENETIC PREDISPOSITION
GENE OF MAJOR EFFECT AUTOSOMAL DOMINANT INHERITANCE

GENETIC MODIFYING FACTORS IgG2 RESPONSE AGAINST AAC, IMMUNOGLOBULIN RESONSE AGAINST OTHER BACTERIA

Diagnosis
CLINICAL

MICROBIOLOGIC

GENETIC

Clinical diagnosis
clinical examination, medical and dental history
more advanced aids are to properly diagnose, treatment plan and monitor the disease.

QUESTIONS TO BE ANSWERED
is there periodontitis is there loss of periodontal support is there a plausible cause for attachment loss other than periodontitis
.

Is there process imitating periodontal disease by pseudo pocket formation. recognize different causes for the attachment loss must rule out other causes attachment loss
.

Orthodontic consideration are necessary

clinical diagnosis.

Incidental attachment loss

What it is???
Conditions ..

The question here is does the patient have a systemic condition medical history is fundamental

Diagnosis : Periodontal manifestation of systemic disease

Exclusion of the systemic disease exclusion of the rare but clearly but clearly identified necrotizing / ulcerative forms. If both are negative, differential diagnosis between chronic and aggressive periodontitis . Diagnosis of AgP is made on the basis of the criteria established for it.

differential diagnosis between LAP and GAP exclusion of the presence of modifying factors/ contributory factors such as smoking and drug abuse

Microbiologic diagnosis
presence of AAC - secondary feature of AgP. successful treatment of LAP depends on

the elimination of the bacterium AAC.

useful at different stages of the treatment plan, initial

diagnosis, at revaluation or during the recall phase.

have no influence on the way as initial treatment is

performed, microbiologic testing may be postponed until the first phase is completed.

Microbiological diagnosis
But the reduction in the bacterial load -false negative result

If the specific clinical diagnosis is LAP - a maximal

suppression of AAC.
microbial testing of spouse, children or siblings of AgP

patients may be indicated to intercept early disease in susceptible individuals.

Evaluation of host response

Both LAP and GAP - phagocyte functional disturbances Different form of AgP - specific pattern of host response to

bacterial pathogens AgP patients have higher level of PGE2 in GCF( indicating that monocytes from these patients respond to bacterial and inflammatory stimuli with very high level of local release of inflammatory mediators). These may induce an exuberant reaction associated with high level of activation of tissue degrading matrixmetalloproteinases.

Evaluation of host response

GAP patients have decreased ability to mount high titre of

specific IgG2 antibodies to AAC.

tendency towards progressive periodontal destruction

leading to tooth loss over a relatively short period of time.

LAP patients have better prognosis and do not express this

trait.
Some of the LAP cases may progress to GAP, so early

detection of patients infected with Actinobacillus actinomycetemcomitans producing low level of specific antibodies may indicate early identification of high risk group for GAP.

Genetic diagnosis
Evaluation of siblings of the probands

and other family members should be done. construction of a pedigree of the AgP trait. Such diagnosis may bring considerable information regarding the level of risk shared with the family and helps to establish the need for monitoring clinically unaffected individuals.
All the evidences gathered during

the diagnostic process should contribute to the definition of a specific diagnosis.

Therapeutic modalities

Early detection.

initial diagnosis-radiographs to assess the rate of progression of the disease. future radiographs - facilitate the clinician assesment of treatment success and control of the disease.

therepeutic modalities.
Educate the patient about the disease & family members therapeutic considerations

-control the infection, -arrest the disease progression, -correct anatomic defects, replace the missing tooth

therapeutic modalities.
Conventional periodontal therapy Surgical resective therapy Regenerative therapy Antimicrobial therapy Microbial testing Local delievery Host modulation Treatment planning and restorative consideration

Use of dental implants

Outcome Assessment
1. Significant reduction of clinical signs of gingival
inflammation; 2. Reduction of probing depths; 3. Stabilization or gain of clinical attachment; 4. Radiographic evidence of resolution of osseous lesions; 5. Progress toward occlusal stability; 6. Progress toward the reduction of clinically detectable plaque to a level compatible with periodontal health.

conclusion