aggressive periodontitis, its pathogenesis, risk factors, differential diagnosis, radiographic and clinical aspects of the disease, its management and how's it different from chronic form of periodontitis recent studies, schoransky's postulates, biomarkers genetic predisposition of the disease

1. AGGRESSIVE
PERIODONTITIS
PRESENTED BY:- DR. SHALINI DUBEY

2. CONTENTS
 HISTORICAL BACKGROUND
 INTRODUCTION (CLASSIFICATION & SUB-CLASSIFICATION; PRIMARY &
SECONDARY FEATURES)
 ETIOLOGY & PATHOGENESIS
 BACTERIAL DAMAGE TO PERIODONTITIS
 HOST RESPONSE TO BACTERIAL PATHOGENS
 CLINICAL DIAGNOSIS
 PRINCIPLES OF THERAPEUTIC INTERVENTION
 CONCLUSION

3. HISTORICAL BACKGROUND
 In 1999, AAP INTERNATIONAL WORKSHOP named it
“Aggressive Periodontitis”

4.  Aggressive Periodontitis refers to the multifactorial, severe &
rapidly progressive form of periodontitis, which primarily but
not exclusively affects younger adults. (Int’l Workshop
Classification of Periodontal Disease & Conditions)

6. Baer proposed 7 criteria to define the disease:-

12. CLASSIFICATION AND CLINICAL
SYNDROMES
 Aggressive forms of periodontal disease have been defined
based on the following primary features. Lang et al (1999):

13. SECONDARY FEATURES
 Amounts of microbial deposits inconsistent
with the severity of periodontal tissue
destruction.
 Elevated proportions of Aggregatibacter
actinomycetamcomitans and in some Far
East populations, Porphyromonas gingivalis.
 Phagocyte abnormalities.
 Hyper-responsive macrophage phenotype,
including elevated proportions of PGE2, IL-
1b.
 Progression of attachment loss and bone
loss may be self arresting.

14. Subclassification of AgP (International
classification Workshop)
LOCALISED AGGRESSIVE PERIODONTITIS (LAP) :-
 Circumpubertal onset
 Localised first molar/incisor presentation with interproximal
attachment loss on atleast two permanent teeth, one of which is a
first molar, and involving no more than two teeth other than first
molars and incisors.
 Robust serum antibody response to infecting agents.

16.  A striking feature is lack of clinical
inflammation despite the presence
of deep periodontal pockets and
advanced bone loss.
 Plaque on the affected teeth is
minimal.
 The plaque that is present forms a
thin biofilm on the teeth and rarely
mineralizes to form calculus.

17.  Distolabial migration of maxillary incisors with diastema formation.
 Increasing mobility of maxillary and mandibular incisors and first molars.
 Sensitivity to denuded root surfaces to thermal and tactile stimuli.
 Deep dull radiating pain during mastication probably caused by irritation of
the supporting structures by mobile teeth and impacted food.

18.  Vertical loss of alveolar bone around the first molars and incisors beginning
around puberty- classic diagnostic sign of LAP
 Arc shaped loss of alveolar bone extending from distal surface of second
premolar to mesial surface of second molar.

19. The following possible reasons for the limitation of
periodontal destruction to certain teeth have been
suggested:
 After initial colonization of first permanent teeth
to erupt, A.a evades the host defences by different
mechanisms including production of PMN
chemotaxis-inhibiting factors, endotoxins,
collagenases, leukotoxins and other factors that
allow the bacteria to colonize the pocket and
initiate destruction of periodontal tissues.
 After this initial attack, adequate immune defenses
are stimulated to produce opsonic antibodies.
 To enhance the clearence and phagocytosis of
invading bacteria and neutralise leukotoxic
activity.
 In this manner, colonization of other sites may
be prevented.

20.  Bacteria antagonistic to Aggregatibacter actinomycetamcomitans colonize
the periodontal tissues and inhibit Aggregatibacter actinomycetamcomitans
from further colonization therefore localizing A.a infection and tissue
destruction.
 Aggregatibacter actinomycetamcomitans may lose its leukotoxin-producing
ability; progression becomes arrested or impaired and colonization of new
sites may be averted.
 A defect in cementum formation may be responsible for localization of
lesions.

21. GENERALIZED AGGRESSIVE
PERIODONTITIS (GAP)
 Usually affecting persons< 30 yrs; may be older.
 Generalized interproximal attachment loss affecting atleast
three permanent teeth other than first molars and incisors.
 Pronounced episodic nature of destruction of attachment and
alveolar bone.
 Poor serum antibody response to infecting agent.

22. Two types of gingival responses seen:
 Severe, acutely inflamed tissues, often proliferating, ulcerated and fiery red.
(DESTRUCTIVE STAGE )
Bleeding may be spontaneous or with slight stimulation. Suppuration may be an
important feature.
 Tissues may appear pink, free of inflammation, and occasionally with some
degree of stippling.
Page and Schroeder believed that this type of response coincides with periods
of quiescence in which bone levels remain stationary.
Systemic manifestations can be seen like fever, weight loss, mental depression,
and general malaise.

23. Radiographically
 Can range from severe bone loss associated with minimum number of teeth
to advanced bone loss affecting the majority of teeth in the dentition.

24. ETIOLOGY AND PATHOGENESIS
Dominant microorganisms in LAP :
 Aggregatibacter actinomycetamcomitans, Capnocytophaga
sp., Eikenella corrodens, Prevotella sp., Campylobacter rectus.
 Gram positive isolates : streptococci, peptostreptococci.
 Aggregatibacter actinomycetamcomitans, Capnocytophaga,
Prevotella sp. Are predominant members of subgingival flora.

25. Aggregatibacter actinomycetamcomitans
Key microorganism in LAP.
 Short, facultatively anaerobic, non-
motile, gram negative rod.
 This view was principally based on four
lines of evidence (Socransky & Haffajee
1992):
 Aggregatibacter actinomycetamcomitans
was isolated in more than 90% of LAP
patients. In some studies, it was possible to
demonstrate elevated levels of A.a in sites
showing evidence of recent or ongoing
periodontal tissue destruction (Haffajee et al
1984; Mandell 1984; Mandell et al 1987.)

26.  Aggregatibacter actinomycetamcomitans produces several potentially
pathogenic substances, including leukotoxin and is capable of inducing
disease in experimental animals and non-oral sites. It can translocate across
epithelial membranes. ( Zambon et al 1988, Slots & Schonfeld 1991).
 Findings of immune response towards this bacterium: elevated levels of
serum antibodies to Aggregatibacter actinomycetamcomitans in LAP patients
(Listgarten et al 1981, Tsai et al 1981, Altman et al 1982, Ebersole et al 1982).
 Clinical studies showing correlation between treatment outcomes and levels
of Aggregatibacter actinomycetamcomitans after therapy: unsuccessful
treatment outcomes linked to failure in reduction of subgingival load.

27.  Using monoclonal antibody technology, five serotypes (a,b,c,d,e) of
Aggregatibacter actinomycetamcomitans can be distinguished.
 Serotype b strains often isolated from patients with localized juvenile
periodontitis than from other subjects (Zambon et al 1983, 1996).
 Several properties of Aggregatibacter actinomycetamcomitans are regarded
as important determinants of virulence and pathogenic potential.
 Leukotoxin production is considered highly significant since it may play
important role in A.a’s evasion of local host defences.

28. LEUKOTOXIN: role in evasion of local host defences.
 Belongs to family of RTX (Repeats in ToXin), which are pore-forming lytic
toxins.
 Exhibits cytotoxic specificity and destroys human PMN leukocytes and
macrophages, but neither epithelial and endothelial cells, nor fibroblasts.
 Serotype-b strain (JP2 Clone) present in high frequency in patients with LJP.
This strain was isolated from African American child with prepubertal
periodontitis (Tsai et al 1984).

30.  Gram negative bacteria consists of lipopolysaccharide (LPS).
 A.a can secrete membrane vesicles that can serve as transport vehicles to
spread endotoxin as well as other pathogenic substances produced by
bacterium.
 LPS can activate host cells & macrophages to secrete inflammatory mediators
such as Prostaglandins, IL-1b, TNF-a.
 It is highly immunogenic, since high titers of antibodies against its antigenic
determinants are frequently detected in infected individuals

31. Dominant organisms in GAP
 Porphyromonas gingivalis, Bacteroides
forsythus and A.a.
 A.a is facultative anaerobe; P.gingivalis
and B. forsythus are fastidious strict
anaerobes.
 P. gingivalis produce collagenases,
proteases, endotoxins, fatty acids, other
possibly toxic agents (Shah 1993).
 High local and systemic immune
responses against this bacterium have
been demonstrated in patients with GAP.

32. BACTERIAL DAMAGE TO PERIODONTIUM
 Two related mechanisms:
 Direct action of the microorganism or their products on the
host tissues.
 Results of the eliciting tissue damaging inflammatory
responses.
 Investigations have indicated that A.a is able to
translocate through junctional epithelium and invade
the underlying connective tissue (Saglie et al 1988).

33.  Apical spread of bacteria loosely adhering to hard, non
shedding surface of tooth is thought to be controlled through
first line of defence.
Mechanisms:
 High turnover rate of junctional epithelium keratinocytes.
 Outward flow of GCF.
 Directed migration of PMN leukocytes through junctional
epithelium.

34. HOST RESPONSE TO BACTERIAL
PATHOGENS
 Local inflammatory response characterized by intense
recruitment of PMNs both within the tissues and into
periodontal pocket.
 Depressed T-helper cell to T-suppressor cell ratio
compared to both healthy gingiva and peripheral blood.
 High levels of PGE2, IL-1a, IL-1b in both crevicular fluid
and peripheral blood.
 Prostaglandin E2 production is highly elevated in AgP
subjects when compared to periodontally healthy
individuals and chronic periodontitis patients.

35. IMMUNOLOGICAL FACTORS
 The human leukocyte antigens (HLAs), which regulate immune responses,
have been evaluated as candidate markers for aggressive periodontitis.
 HLA A9, B15 antigens are consistently associated with aggressive
periodontitis.
 Patients with aggressive periodontitis display functional defects of
polymorphonuclear leukocytes (PMNs), monocytes, or both.
 These defects can impair either the chemotactic attraction of PMNs to the
site of infection or their ability to phagocytose and kill microorganisms.
 Current studies demonstrate hyper responsiveness of monocytes from LAP
patients involving the production of PGE2 in response to Lipopolysaccharide.
 This lead to increased connective tissue or bone loss due to excessive
catabolic factors.

36. Possible immune mechanisms include
 Increase in expression of MHC II, HLA DR4.
 Polyclonal activation of B cells by microbial plaque.
 Genetic predisposition.

37. GENETIC ASPECTS OF HOST
SUSCEPTIBILITY
 SEGREGATION ANALYSIS : autosomal dominant inheritance.
 Segregation analysis provides information about the mode
of inheritance of a genetic trait but not about the specific
gene involved.
 LINKAGE ANALYSIS: linkage of LAP to Vitamin D binding
locus on region q of chromosome 4 in large family of
Brandywine population (Boughman et al 1986).
 Li et al 2004 : has shown linkage of LAP with q25 region of
chromosome 1.
 Scapoli et al 2005: showed linkage with q13-14 region of
chromosome 2 that contains IL-1 gene complex.

38.  Tonetti and Mombelli,1999 summarized that “it seems that
specific genes may be different in various populations and/or
ethnic groups and therefore true heterogeneity in disease
susceptibility may be present.
 The role of specific genes remains to be elucidated”.

39. ENVIRONMENTAL ASPECTS OF HOST
SUSCEPTIBILITY
 Cigarette smoking was shown to be a risk factor for patients with GAP.
(Schenkein et al 1995).
 Smokers with GAP have more affected teeth and greater means of
attachment loss than patients with GAP who did not smoke.
The results indicated that IgG2 levels as well as antibody
levels are significantly depressed in subjects with GAP who
smoke.
Since these antibodies are considered to represent a
protective response against A.a, it is possible that the
depression of IgG2 in smokers may be associated with the
observed increase in disease extent and severity.

40. CLINICAL DIAGNOSIS
A tentative clinical diagnosis is based on following criteria:
 Absence of significant systemic conditions.
 Rapid attachment loss and bone destruction.
 Familial aggregation of cases.
 Lack of consistency between clinically visible bacterial deposits
and severity of periodontal breakdown.

41. PRINCIPLES OF THERAPEUTIC
INTERVENTION
 Treatment should be initiated after completion of careful
diagnosis.
 Successful treatment is considered to be dependent on early
diagnosis, directing therapy towards elimination or
suppression of infecting organisms and providing an
environment conducive to long-term maintenance.

42. The prognosis depends on
 Whether the disease is generalized or localized.
 Degree of destruction present at the time of diagnosis.
 Ability to control future progression. GAP rarely undergoes
spontaneous remission, whereas LAP have been known to
arrest spontaneously. This has been referred to as
“BURNOUT” OF THE DISEASE.

43. CONVENTIONAL PERIODONTAL THERAPY
 Consists of patient education, oral hygiene improvement,
scaling and root planing and regular recall maintenance.
 Teeth with moderate to advanced attachment loss and bone
loss often have a poor prognosis.
 Treatment options for teeth with deep periodontal pockets
and bone loss may be non-surgical or surgical.
 Surgery may be purely resective, regenerative or a
combination.

44. RESECTIVE SURGICAL THERAPY
 Reduces or eliminates pocket depth.
 If a significant height discrepancy exists between periodontal
support of affected teeth and unaffected teeth, the gingival
transition will often result in deep probing pocket depth
around affected tooth.
 It is important to realize the limitations of surgical therapy and
to appreciate the possible risk that surgical therapy may
further compromise teeth that are mobile because of
extensive loss of periodontal support.

45. REGENERATIVE PERIODONTAL THERAPY
 Use of barrier materials, bone grafts, and wound healing
agents.
 Intrabony defects, particularly vertical defects with multiple
osseous walls are often amenable to regeneration with these
techniques.
 Recent advances in regenerative therapy have advocated the
use of enamel matrix derivative (Emdogain) to aid in
regeneration of cementum and new attachment in
periodontal defects.

46. ANTIMICROBIAL THERAPY
SYSTEMIC ADMINISTRATION
 Adjunctive antibiotic treatment frequently
results in a more favorable clinical response
than mechanical therapy alone.
 In a systematic review, Herrera et al found
that systemic antimicrobials in conjunction
with scaling and root planing offer benefits
over scaling and planing alone in terms of
clinical attachment level, probing pocket
depth, and reduced risk of additional
attachment loss.

47.  Genco et al treated localized aggressive periodontitis patients
with scaling and root planing plus systemic administration of
tetracycline (250 mg four times daily for 14 days every 8
weeks).
18 months after the initiation of therapy.
Bone loss had stopped, and one-third of the defects demonstrated
demonstrated an increase in bone level, whereas in the control
control group, bone loss continued.

48.  Liljenberg and Lindhe treated also treated LAP with administration of tetracycline
(250 mg 4 times daily for 2 weeks), modified widman flaps, and periodic recall visits
every month for 6 months. The lesions healed rapidly and more completely.
 After 5 years they found that the treatment group continued to demonstrate
 resolution of gingival inflammation,
 gain of clinical attachment,
 refill of bone in angular defects.
 Systemic antibiotics should only be administered as an adjunct to mechanical
debridement because IN UNDISTURBED SUBGINGIVAL PLAQUE, THE TARGET
ORGANISMS ARE EFFECTIVELY PROTECTED FROM ANTIBIOTIC AGENT DUE TO
BIOFILM EFFECT.

49.  Systemic tetracycline (250mg of tetracycline hydrochloride
four times daily for atleast 1 week) should be given in
conjunction to local mechanical debridement.
 Doxycycline 100mg/day may be used instead of tetracycline.
 Chlorhexidine rinses should be prescribed and continued for
several weeks to enhance plaque control and facilitate
healing.

50.  Antibiotics have been essentially used in two ways for
treatment:
 In combination with intensive instrumentation over a short period of
time after achievement of adequate plaque control in pretreatment
motivation period.
 As a staged approach after completion of initial therapy.

52.  A randomised controlled clinical trial has provided evidence of a significant
benefit arising from treatment approach (Guerrero et al. 2005):
 Achievement of adequate supragingival plaque control (less than 25% sites with
detectable plaque).
 Subgingival instrumentation for 2-day period.
 An adjunctive systemic antibiotic regime consisting of metronidazole (500 mg tid
for 7 days) combined with amoxicillin (500 mg, tid for 7 days)

53. LOCAL DELIVERY
 FORMULATED IN FORM OF SOLUTIONS,
GELS, CHIPS, FIBRES . Advantages:
 Smaller dosages can be administered inside the
pocket.
 No side effects of systemic therapy.
 Increased exposure of the target microorganism
to high concentration therefore more
therapeutic levels of medication.

54. FULL MOUTH DISINFECTION
 Described by Quirynen et al.
 Full mouth debridement completed in two appointments
within a 24 hr period.
 In addition to scaling and root planing, the tongue is brushed
with a chlorhexidine gel (1%) for 1 minute, the mouth is rinsed
with a chlorhexidine solution (0.2%) for 2 minutes, and pockets
are irrigated with 1% chlorhexidine solution.

55. HOST MODULATION
 Administration of agents that modulate the host response.
 Subantimicrobial dose doxycycline (SDD) : help to prevent the destruction of
PDL attachment by controlling the activation of MMP’s, primarily collagenase
and gelatinase, from both infiltrating cells and resident cells of periodontium,
primarily neutrophils.
 SDD as an adjunct to repeated mechanical debridement resulted in clinical
improvement in patients with generalized aggressive periodontitis.
 Other agents such as flubriprofen, indomethacin, and maproxen may reduce
inflammatory mediator production.

56. CONCLUSION
 Aggressive periodontitis comprises a group of rare, often
severe, rapidly progressive forms of periodontitis ,
characterised by an early age of onset and tendency for cases
to aggregate in the families.
 Diagnosis of one of these forms requires the absence of
systemic diseases that may severely impair host defences and
lead to premature exfoliation of teeth.
 Optimal plaque control by patient is of paramount importance
for a favourable clinical and microbiological response to
therapy.

57. REFERENCES
 Carranza, 10th & 12th edition
 Albandar, J. M. (2014), aggressive periodontitis: case defition and diagnostic
criteria. Periodontology 2000, 65: 13-25
 Kӧnӧnen, E. and Muller, H. P. (2014), microbiology of aggressive periodontitis.
Periodontology 2000, 65: 46-78
 Kulkarni, C. and Kinane, D. F. (2014), Host response in aggressive
periodontitis. Periodontology 2000, 65: 79-91
 Teughels, W., Dhondt, R., Dekeyser, C. and Quirynen, M. (2014), treatment of
aggressive periodontitis. Periodontology 2000, 65: 107-133

58. THANK YOU