Aggressive periodontitis

Aggressive Periodontitis

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 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


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


Diastema

Increasing mobility

Sensitivity

Deep, dull, radiating pain

Periodontal abscesses

Regional lymph node enlargement


‘Burn out’ of disease

Baer (1971)

Stable disease

Gunsolley (1995)

Periodontal diseases : Episodic phenomenon


Radiographic features

Vertical bone loss

Arch shaped loss


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


Poor antibody response

Occurs episodically

Two gingival responses

Systemic manifestations

Acutely inflamed tissue Free of

inflammation


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


Microbial etiology

LAP

A.a, Capnocytophaga sp, Eikenella corrodens, Prevotella sp,

Campylobacter rectus

Streptococci, actinomycetes, peptostreptococci

GAP

P.g, A.a, T.f


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


Archaea : Prokaryotes that physically resemble bacteria

29.4% aggressive periodontitis patients

Yamabe 2008

68% GAP sites

Methanobrevibacter oralis

Environmental modifier

Matarazzo et al.2011


Viral etiology

EBV & CMV

LAP : Odds ratio

Michalowicz 2000

Cytomegalovirus : 6.6 P. gingivalis : 8.7

Cytomegalovirus + P. gingivalis : 51.4


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


Active CMV infection were heavily infected with A.a as compared

to latent infection.

73% - 78% GAP : HSV1, EBV & CMV

Saygun 2004


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


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


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)


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


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


Oxidative burst products : Superoxide, hydroxyl radicals &

hydrogen peroxide

Inherent / Acquired


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


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


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


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


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


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

Host defense

evaluation

Clinical

Micro-biological


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


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


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


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


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


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


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


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.


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.

Aggressive periodontitis

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