Content
 Introduction
 History
 Classification & Clinical Features
 Epidemiology
 Localized Aggressive Periodontitis
 Generalized Aggressive Periodontitis
 Histopathology
 Etiology and Pathogenesis
 Diagnosis and Treatment
 Conclusion
 References

Introduction
Group of rare, often severe, rapidly progressive forms of
periodontitis often characterized by an early age of clinical
manifestation and a distinctive tendency for cases to
aggregate in families

History
Terminology Investigator Year
Diffuse atrophy of alveolar bone Gottlieb 1923
Deep cementopathia Gottlieb 1928
Paradontitis marginalis progressiva Wannenmacher 1938
Paradontosis Thoma & Goldman 1940
Periodontosis Orban & Weinmann 1942
Acute juvenile periodontitis Chaput 1967
Juvenile periodontitis Butler 1969

History
Localized generalized periodontosis Baer 1971
Periodontitis complex Box 1972
Localized periodontosis Fourel 1972
Gottlieb syndrome Fourel 1974
Destructive juvenile periodontitis Waerhaug 1977
Periodontosis Baer & Kaslick 1978
Juvenile periodontitis Page & Schroeder 1982
“A disease of the periodontium occurring in an otherwise healthy
adolescent which is characterized by a rapid loss of alveolar bone
about more than one tooth of the permanent dentition. The amount
of destruction manifested is not commensurate with the amount of
local irritants.”
Baer 1971

History
 Early Onset Periodontitis
 Prepubertal periodontitis
 Juvenile periodontitis
 Rapidly progressive periodontitis
Caton, 1989 World Workshop in Clinical Periodontics
 Aggressive Periodontitis
Lang , 1999 International Workshop for
Classification of Periodontal Diseases

Classification & Clinical features
Primary features
Clinically healthy
Rapid attachment loss
& bone destruction
Familial aggregation
Secondary features
Inconsistent amounts of microbial
deposits
Elevated proportions of A.a, P.g
Phagocyte abnormalities
Hyper-responsive macrophage
phenotype
Progression of attachment & bone
loss may be self-arresting
Lang et al, 1999

Classification & Clinical features
 Localized Aggressive Periodontitis (LAP)
 Generalized Aggressive Periodontitis (GAP)
Lang et al. 1999; Tonetti & Mombelli 1999

Epidemiology
 Rapid progression : 8%
Loe 1986
 Adolescents (14 - 17yrs) : 0.13%
Loe 1991
 LAP : < 1% (0.2% - 2.6%)
Loe & Brown 1991
 Black males > Black females >White females > White males
Melvin 1991
 Individuals < 35 years : 1% - 15%
Demmer & Papapanou 2010

Epidemiology
 Madras : 0.01% Miglani et al. 1965
 Bombay : 6.80% Rao et al. 1968
17.60% Day et al. 1949

Localized Aggressive Periodontitis
 Localized distribution of lesions
 Adequate immune defenses after initial colonization
Zambon 1983
 Bacteria antagonistic to A.a may colonize periodontal tissues
Hillman 1982
 A.a might lose its leukotoxin producing ability
Slots 1982
 Defect in cementum formation
Page 1985

Localized Aggressive Periodontitis
 Lack of clinical inflammation
 Deep periodontal pockets
 Gingival index, gingival bleeding & suppuration scores
Burmeister et al. 1984
 Minimal amount of plaque
 Elevated levels of A.a & P.g
 Rate of bone loss : 3 - 4 times faster
Baer 1971

Localized Aggressive Periodontitis
 Diastema
 Increasing mobility
 Sensitivity
 Deep, dull, radiating pain
 Periodontal abscesses
 Regional lymph node enlargement

Localized Aggressive Periodontitis
 ‘Burn out’ of disease
Baer (1971)
 Stable disease
Gunsolley (1995)
 Periodontal diseases : Episodic phenomenon

Localized Aggressive Periodontitis
 Radiographic features
 Vertical bone loss
 Arch shaped loss

Generalized Aggressive Periodontitis
 Attachment loss ≥ 8 teeth, at least 3 of which were not 1st molars
or incisors
Burmeister et al. 1984
 Generalized interproximal attachment loss affecting at least 3
permanent teeth other than first molars & incisors
Lang, AAP Consensus Report,1999
 Plaque : Inconsistent
 P.g, A.a, T.f

Generalized Aggressive Periodontitis
 Poor antibody response
 Occurs episodically
 Two gingival responses
 Systemic manifestations
Acutely
inflamed tissue Free of
inflammation

Generalized Aggressive Periodontitis
 Radiographic features

Histopathology
 Plasma cell-dominated inflammatory infiltrate
 PMNs migrates through pocket-lining epithelium
 Layer between tissues and plaque biofilm
 Root surfaces : Abundant (Fine et al.1984, Rams et al. 1984)
 Infiltrated connective tissue : Very low (Lijenberg 1980)

Histopathology
 Plasma cells entering an apoptotic phase
 IgG
 IgM & IgA levels
Van Swol et al. 1980
 Cementum hypoplasia
 Absence of reparative cementum

Etiology & Pathogenesis
Factors
Microbial
Immunological
Genetic
Environmental

Etiology & Pathogenesis
Microbial etiology
 LAP
 A.a, Capnocytophaga sp, Eikenella corrodens, Prevotella sp,
Campylobacter rectus
 Streptococci, actinomycetes, peptostreptococci
 GAP
 P.g, A.a, T.f

Etiology & Pathogenesis
 A.a is the key microorganism in LAP
 > 90% of LAP sites (Slots et al, 1990)
 Disease progression show elevated levels of A.a (ie ongoing
sites – haffajee et al, 1994)
 Virulence factors (like leukotoxin) – Zambon, 1988
 Elevated serum antibody titers to A.a ( Listgarten, 1981)
 Reduction in subgingival load of A.a during treatment
(Haffajee et al, 1994)
Socransky & Haffajee 1992, Tonetti & Mombelli1999

Etiology & Pathogenesis
 Archaea : Prokaryotes that physically resemble bacteria
 29.4% aggressive periodontitis patients
Yamabe 2008
 68% GAP sites
 Methanobrevibacter oralis
 Environmental modifier
Matarazzo et al.2011

Etiology & Pathogenesis
Viral etiology
 EBV & CMV
 LAP : Odds ratio
Michalowicz 2000
Cytomegalovirus : 6.6 P. gingivalis : 8.7
Cytomegalovirus + P. gingivalis : 51.4

Etiology & Pathogenesis
 Herpesvirus like virions found signifying active viral infection.
Burghelea,1990
 Primary CMV infection at time of root formation : Defective
periodontium
Ting et al. 2000
 CMV infection early in life : Cemental hypoplasia
 Reactivation during hormonal changes during puberty:
Suppression of antibacterial immune defenses, increaing chancesof
infection
Slots 2010

Etiology & Pathogenesis
 Active CMV infection were heavily infected with A.a as compared
to latent infection.
 73% - 78% GAP : HSV1, EBV & CMV
Saygun 2004

Etiology & Pathogenesis
 Herpesvirus infection : Pathogenicity of periodontal microbiota
 Direct cytopathic effects
 CMV : Enhance adherence of A.a
 Induce abnormalities in PMNs
 EBV : Neutropenia & stimulate proliferation of B-lymphocytes
 Up-regulate the IL-1β & TNF-α gene expression of monocytes &
macrophages
Slots 2010

Etiology & Pathogenesis
Immunological factors
 Intense recruitment of PMNs : Tissues & Pocket
 B cells & plasma cells : Connective tissue lesion
Liljenberg & Lindhe 1980
 Plasma cells : IgG-producing cells
 Local inflammatory infiltrate : T cells
 Depressed T-helper to T suppressor ratio
 PGE2, IL-1α, IL-1β
Masada et al. 1990, Offenbacher et al. 1993

Etiology & Pathogenesis
Impaired Neutrophil Model in Aggressive Periodontitis
 Reduced chemotaxis to f- Met- Leu- Phe (72% - 86%)
Lavine 1979, Page 1984,1985, Altman 1985
 Reduced chemotaxis without f- Met- Leu- Phe stimulation
Page 1993
Reduction in number
of receptors
Defect in f-Met-Leu-Phe receptor or
co-receptors (GP110 or CD38)

Etiology & Pathogenesis
 Impaired phagocytosis & killing
 LAP (53%) & GAP (46%) : % of PMNs with phagocytosed
particles & numbers of phagocytosed particles per PMN
Kimura et al 1992
 GCF : LL-37 cathelicidin & peptide 1-3 defensin
Puklo et al 2008
 Polymorphisms in Fcγ receptor : Phagocytosis of
periodontopathic bacteria
Kaneko 2004, Nibali 2006

Etiology & Pathogenesis
Concept of a Hyperactive or Primed Neutrophil
 Hyperactive ⁄ primed neutrophil : Tissue destruction
Kantarci et al 2005
 Increased intracellular levels of beta-glucuronidase
Pippin 2000
 Baseline levels of myeloperoxidase : Correlated with bleeding &
suppurating sites
Kaner 2006

Etiology & Pathogenesis
 Oxidative burst products : Superoxide, hydroxyl radicals &
hydrogen peroxide
 Inherent / Acquired

Etiology & Pathogenesis
Genetic factors
 Familial Aggregation
 US survey (1996) of 7447 dentate individuals : 40% - 50%
siblings in families similarly affected
 Segregation Analyses
 Dominant + Recessive
 Autosomal dominant : Largest study in U.S. in African-American
& Caucasian families
Marazita et al 1994

Etiology & Pathogenesis
 Linkage Analysis
 Vitamin D binding locus on 4q in a large family of Brandywine
population Boughman et al. 1986
 q25 region of chromosome 1 in an area close to COX-2 gene
Li et al. 2004
 Chromosome 2q13–14 that contains the IL-1 gene complex
Scapoli et al. 2005

Etiology & Pathogenesis
Gene polymorphisms
 IL-1B +3954
Quappe 2004, Scapolli 2005
 No IL gene polymorphisms : Aggressive periodontitis
Prakash et al 2010, Shete et al 2010
 Vitamin D Receptor RFLP Fok1 : Risk of developing GAP
Li et al 2008

Etiology & Pathogenesis
 Fc γ receptor IIIB NA1/NA1 genotype : Chinese population
Fu 1999, Zhang 2003
 Fc γ receptor IIA R131 allele : Taiwanese population
Chung 2003
 HLA-A9 & -B15 : Aggressive periodontitis
 HLA-A2 & -B5 : Potential protective factors
Shapira et al 1994

Etiology & Pathogenesis
Environmental factors
 Cigarette smoking : Risk factor for GAP
 More affected teeth and greater mean levels of attachment loss
Schenkein et al. 1995
 GAP group : Significantly increased depression & loneliness
Monteiro da Silva 1996

Etiology & Pathogenesis
Microbial exposure & infection
A. a
Environmental modifying factors
Cigarette smoking
P.g & other bacteria
Genetic predisposition
Autosomal dominance inheritance
Genetic modifying factors
IgG2 response against A. a
Immunoglobulin response against other
bacteria
Normal LAP GAP
Environmental Factors
Genetic Factors

Diagnosis and Treatment
Diagnosis
Host
defense
evaluation
Clinical
Micro-
biological

Diagnosis and Treatment
 15-year follow-up study
 LAP : Stabilize over time
 GAP : Increasing amounts of attachment & tooth loss
 LAP : Gain in periodontal attachment with SRP & surgery
Gunsolley et al. 1995

Diagnosis and Treatment
LAP
 Mechanical debridement + chemotherapeutic agents
 Predominant culturable microbiota susceptible to tetracycline
 A.a penetrated pocket epithelium
 Root surface debridement + tetracycline : Successful in treating
most LAP sites
Slots & Rosling 1986

Diagnosis and Treatment
 Rationale for surgery
 Modified Widman flap surgery + tetracycline regimen
Lindhe & Liljenberg 1984, Kornman & Robertson 1985
 Regenerative techniques
 Autogenous grafts
 Freeze-dried bone allograft : Average defect fill 80%
Yukna & Sepe 1982
 GTR Sirirat et al 1996

Diagnosis and Treatment
GAP
 SRP : 1 mm reduction in probing depth and a 0.5 mm gain in
attachment levels
Purucker et al 2001
 Nonsurgical root surface debridement : Mean reduction in probing
depth of 2.11 mm & mean attachment level gain of 1.77 mm
Hughes et al. 2006

Diagnosis and Treatment
 SRP + Metronidazole & amoxicillin : Sites > 7 mm, additional 1.4
mm reduction in PD & 1 mm gain in attachment level
 Disease progression at 6 months : 1.5% of sites in patients of
antibiotic group & 3.3% of sites in controls
Guerrero et al. 2007
 Metronidazole & clindamycin significantly improved the clinical
response
Sigusch et al. 2001

Diagnosis and Treatment
 Metronidazole ⁄ amoxicillin 6 weeks after SRP : PD > 6 mm
significantly reduced
Xajigeorgiou et al. 2006
 Immediately after SRP
Kaner et al. 2007
 Tetracycline fibers + SRP > SRP
Sakellari 2003

Diagnosis and Treatment
SRP + Systemic antibiotics (24 h before SRP)
Re-evaluation at 4- 6 weeks
Resolution of disease indicators No significant positive response
Maintenance / Surgical phase Initial phase
Culture & sensitivity
Subgingival scaling + Different antibiotic regimen
Deas & Mealey 2010

Diagnosis and Treatment
 Surgical modalities
 Maintenance program – call pt every1month for 6 motnhs, then
call every 2 months for 6 months following which call every 3
months
 Isolated sites of recurring disease – SRP of that site n tetracycline
fibers
 Generalized recurrence- full mouth SRP + systemic antibiotics.

Diagnosis and Treatment
 Implants
 Survival rate : 56% -100%
Malmstrom et al 1990, Mengel et al 2005
 >90%
 Impaired host response
 Lower implant survival rates
 After controlling dental & periodontal diseases
Al-Zahrani 2008

Conclusion
 Thorough understanding of the etiopathogenesis and clinical
features of aggressive periodontitis and the therapeutic
approaches available is essential to provide the patient with the
best chances of successful treatment outcomes

References
 Newman MG, Takei HH, Klokevold PR, Carranza FA. Carranza’s
Clinical Periodontology. Saunders Elsevier;10th Edition.
 Lindhe, Karring, Lang. Clinical Periodontology & Implant Dentistry.
Blackwell Munksgaard; 5th Edititon.
 Armitage GC, Cullinan MP, SeymourGJ. Comparative biology of
chronic and aggressive periodontitis: introduction. Periodontol 2000
2010;53.
 L A Wisner-Lynch, W V Giannobile. Current concepts in juvenile
periodontitis. Current opinion in Periodontology 1993: 28-42.

References
 Lang N, Bartold PM, Cullinas M et al. Consensus report: Aggressive
periodontitis . Ann Peridontol 1999; 4: 32-37.
 Meng H, Xu L, Li Q, Han J, Zhao Y. Determinants of host
susceptibility in aggressive periodontitis. Periodontol 2000
2007;43:133-59.
 Ryder MI. Comparison of neutrophil functions in aggressive and
chronic periodontitis. Periodontol 2000 2010;53: 124-137.
 Al-Zahrani MS. Implant therapy in aggressive periodontitis patients:
a systematic review and clinical implications. Quintessence Int. 2008
Mar;39(3):211-215.