Localized Aggressive Periodontitis (LAP): by OrBI869

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									   Localized Aggressive
     Periodontitis (LAP):




By: Rebecca Goldberg, Pediatric Dentistry
    What is Localized Aggressive Periodontitis
                      According to Dr. Joseph Califano, 2003, Position Paper:
                         “Periodontal Diseases of Children and Adolescents

   Rapid and severe loss of alveolar bone around more than one
    permanent tooth, usually the first molars and incisors
   Characterized by interproximal attachment loss on at least 2
    permanent first molars and incisors, with attachment loss on no
    more than 2 teeth other than first molars and incisors
   Frequently disease is localized to permanent molars and incisors,
    however some retrospective data on LAP patients suggest that
    findings of bone loss around primary teeth can be early finding in
    disease
   Occurs in otherwise healthy children and adolescents without
    clinical evidence of systemic disease
   Patients have little or no tissue inflammation and very little
    supragingival dental plaque or calculus
          Rates of Bone Loss Progression
 Adult Periodontitis:
 0.072-0.736mm per year


 LocalizedAggressive Periodontitis:
 1.08-1.80mm per year


 *Approximately   5x’s more bone loss per
 year in LAP

                                             3
                    Localized Aggressive
                            Periodontitis




* Term used to be Localized Juvenile Periodontitis (LJP)
                                            Epidemiology
        According to Dr. Terry D. Rees, 2004, American Academy of Pediatric
                                Dentistry: Periodontal Diseases of Children”

   Overall prevalence range in United States is 0.2% to 15%
   Most estimates suggest a low prevalence of 0.2%
   African Americans estimated prevalence greater than 2.5%
   Hispanics estimated prevalence at 1.0%
   Caucasian estimated prevalence at 0.1%
   Incidence increases in adolescents aged 12-17 when
    compared to children 5-11 years old
   Due to influence of race on prevalence of LAP, the risk of this
    disease implies genetic component
    Genetic Defects in LAP Patients
      According to Dr. Harvey Schenkein, 1998, American Academy of
           Periodontology: The Pathogenesis of Periodontal Diseases




            Neutrophil chemotactic defects
    Neutrophil Chemotactic Defects
According to Thomas E. Van Dyke, 1985, “Role of Neutrophil in Oral Disease:
 Receptor Deficiency in Leukocytes from Patients with Juvenile Periodontitis”

 Thefunction of the neutrophil is thought to be
 clearance of infecting organisms and other
 noxious substances
 Theabnormality of chemotaxis in LAP is
 characterized by a decrease in the rate of cell
 migrations in response to a chemotactic
 gradient
 StudyPurpose: Investigate the total binding of
 labeled C5a to LAP neutrophils compared to
 neutrophils of non-LAP patients
     Neutrophil Chemotactic Defects
According to Thomas E. Van Dyke, 1985, “Role of Neutrophil in Oral Disease:
 Receptor Deficiency in Leukocytes from Patients with Juvenile Periodontitis”

   C5a was isolated from human plasma
   These cells were placed in polyethylene tubes containing
    125I-labeled C5a (LAP)


   After incubation at 4˚C the cells were tagged with
    radioactivity
   Results: There was a significant reduction of 125I-labeled C5a
    specifically bound to LAP neutrophils as compared to those
    bound by unlabeled “control” neutrophils
   Results: The number of LAP binding sites for LAP neutrophils
    was 133,000 and 218,000 sites for control neutrophils (~50%
    difference)
Complement Pathways
      Alternative Pathway (Innate Immunity):
      C3b is receptor on PMN’s and acts as docking agent for
      bacteria
      C3b-Bb (C3 Convertase) breaks up C3 into more C3b
      C3b binds to C3 Convertase to form C5 Convertase
      C5 Convertase forms C5b (attaches to LPS to initiate MAC)
      and C5a (chemoattracts PMN’s)
      Classical Pathway (Adaptive Immunity-Humoral):
      Antibodies bound to bacterial agent activates C1
      C1 activates C2 and C4
                   C2 forms C2a and C2b
                   C4 forms C4a and C4b
      Together these form C3 Convertase to break up more C3
      into more C3b
      C3b binds to C3 Convertase to form C5 Convertase
      C5 Convertase forms C5b (attaches to LPS) and C5a
      (chemoattracts PMN’s)
Complement Pathways
                                                What Causes LAP
      According to Graaff, Winkelhoff, Goene, 2000, “The Role of Actinobacillus
               Actinomycetemcomitans in Localized Aggressive Periodontitis”

   Actinobacillus actinomycetemcomitans (A.a.) Characteristics:

   -Gram negative rod
   -Non-spore forming
   -Nonmotile
   -Facultatively anaerobic
   -Isolated mainly from subgingival plaque but may be found in
   supragingival plaque & on mucosal surfaces
   -Normally found in oral flora of 36% of population
   -Found to occur in actively diseased sites at levels 100 fold greater
   than those of the non-actively diseased sites
   * Now known as “Aggregatibacter actinomycetemcomitans
       Aggregatibacter
actinomycetemcomitans
         Aggregatibacter actinomycetemcomitans
  According to Graaff, Winkelhoff, Goene, 2000, “The Role of Actinobacillus
           Actinomycetemcomitans in Localized Aggressive Periodontitis”

         growth of S. sanguis and A. viscous and other
 Inhibits
 supragingival plaque forming organisms through
 bacteriocin (actinobacillin)

 Produces  virulence factors to promote its colonization
 and survival
  • Leukotoxin is the prime virulence factor (other
    virulence factors: collagenase, bone resorption
    inducing factor, catalase positive)

 Fivedistinct serotypes of A.a.
  • Serotype B (Y4) most commonly associated with LAP
     What Does Leukotoxin Do?
KillsPMN’s and monocytes
Inhibits PMN’s functions
Resistant to complement mediated killing
    How Does Leukotoxin Affect Our Cells

   According to Edward Lally, 1997- A.a.’s leukotoxin (RTX) kills
    human immune cells by binding to neutrophils and causing
    cytolysis(cell death)



   According to Yamaguchi, 2001- A.a.’s leukotoxin induces apoptosis
    through a mitochondrial pathway that involves decreased levels of
    ADP in the mitochondrial matrix and arrest of oxidative
    phosphorylation




                                                                        15
                                    Leukotoxin (LTX)
                According to Bruce Shenker, 1988, “Infection and Immunity:
                        Immunosuppressive Properties of A.a. Leukotoxin”

   Study Purpose: To examine A.a.’s leukotoxin (LTX) and its
    ability to alter human lymphocyte function
   HPBLs (Human Peripheral Blood Lymphocytes) from blood of
    healthy donors was centrifuged for 15 minutes at 15˚C
   4 x 107 HPBLs were isolated and then washed 2X with HBSS
    (Hank’s Balanced Salt Soltn)
   These HPBLs were incubated at 37˚C for 90 minutes with
    either (1) LTX, (2) Medium, and (3) Pre-treated LTX with
    neutralizing monoclonal antibody
   The non-viable cells were identified using trypan blue stain
    uptake
                                           Leukotoxin (LTX)
                    According to Bruce Shenker, 1988, “Infection and Immunity:
                            Immunosuppressive Properties of A.a. Leukotoxin”

   Results of Groups 1, 2, 3:
   (1) It was determined that 80-85% of the total monocytes exposed to LTX died
   (2) It was determined that there was no change in cell viability in cultures
    exposed to medium (control)
   (3) It was determined that there was no change in cell viability in cultures
    exposed to pre-treated LTX with monocolonal antibody
          -The monoclonal antibody neutralizes the lethal effects of LTX on
            monocytes
   Note: Although this study determined that pre-treated LTX with monoclonol
   antibody neutralizes A.a.’s leukotoxin virulence factor, it does not have
   an affect on the T-cell immunosuppressor activation ability of A.a.
      How Do You Treat Patient With LAP?
        According to Dr. Terry D. Rees, 2004, American Academy of Pediatric
                                Dentistry: Periodontal Diseases of Children”


   It is common practice that patients with periodontitis are
    given oral hygiene instruction and treated mechanically with
    debridement of dental plaque in subgingival and
    supragingival areas
    • However, the arrest of LAP in this manner was found to be not possible
      due to the inability to eliminate A.a.
    • A theory as to why: Because A.a. invades periodontal tissues and
      epithelium which makes the bacteria less accessible for mechanical
      removal (SRP)

   There is some disagreement among studies on treatment of
    LAP-but most recommend a combination of surgical or non-
    surgical root debridement in conjunction with antibiotic
    therapy
      How Do You Treat Patient With LAP?
    According to Graaff, Winkelhoff, Goene, 2000, “The Role of Actinobacillus
             Actinomycetemcomitans in Localized Aggressive Periodontitis”

   Study: 30 LAP patients were selected and randomly divided
    into 3 different groups
    (1) Consisted of 7 LAP patients receiving IT (initial
         treatment: oral hygiene instruction and mechanical
         debridement of supragingival and subgingival plaque)
    (2) Consisted of 12 LAP patients receiving IT and
         tetracycline as adjuct antimicrobial therapy for 7 days
    (3) Consisted of 11 LAP patients who received IT, and
         adjuct antimicrobial therapy of a combination of
         metronidazole (250mg 3X daily) and amoxicillin (375mg
         3X daily) for 7 days
      How Do You Treat Patient With LAP?
    According to Graaff, Winkelhoff, Goene, 2000, “The Role of Actinobacillus
              actinomycetemcomitans in Localized Aggressive Periodontitis”

   Group (1): All 7 remained colonized with A.a. and
               further progression of disease was observed
   Group (2): After four months, only 5 patients became
               free of A.a.
         These patients clinically gained periodontal attachment and the disease
          was arrested
         The other 7 patients remained colonized with A.a. and no arrest of
          disease was observed

   Group (3): Clinical and microbiological evaluation was
               carried out for 2, 4, and 10 months after
               therapy
         After this therapy, no A.a. could be detected in all 11 patients
     How Do You Treat Patient With LAP?
  According to Graaff, Winkelhoff, Goene, 2000, “The Role of Actinobacillus
            actinomycetemcomitans in Localized Aggressive Periodontitis”

 Results:
 The finding that A.a. was still undetectable after
 10 months of therapy suggests that this treatment
 is effective
 Theclinical condition after treatment of Group (3)
 determined that the probing pocket depth of the
 sampled sites reduced with significantly less
 bleeding
*These findings show that the success of treating
 LAP is associated with the eradication of A.a.
                        LAP Clinical Case
       Tapper Dental Clinic (2007-Present)
   7 year old, Caucasian male presents with only
    medical history of ADHD and chief complaint
    “teeth are mobile”

   Treatment Protocol:
   (1) Biopsy plaque and saliva
   (2) Initial SRP & Prophy
   (3) CHX Periochip in pocket sites
   (4) 10 day course of Ampicillin
   (5) Follow-up with Arestin (minocycline HCL) in
    pocket areas

   *From 9-07 to 10-08 patient returned to clinic
   continuously for SRP and Arestin Injection treatments   22
      Initial Pocket Depths (2007)
                                   Upper

333   222    343   333   323   324    323    722   333   213   313   223


3     A B C 7                  8      9      10 11 I           J     14
412   212    212   212   224   813    324    313   312   212   212   212


                                   Lower

322    222   212   333   212   212     212   212   222   212   212   213


30 T S             R 26 25 24 23 M L                           K 19
322    212   212   212   332   212     212   212   322   122   122   223




                                                                           23
      Final Pocket Depths (2008)
                                   Upper

233   212        333   323   323     323   422   333   213   313   223


3     4          C 7         8       9     10 H I            J     14
312   212        212   223   413     324   313   312   212   212   212


                                 Lower

322   222   PE   333   212   212     212   212   322   212   212   213


30 T 28 R 26 25 24 23 M L                                    K 19
322   212   PE   212   332   212     212   212   222   122   122   223




                                                                         24
                                 March 2011
   11 year old patient presents with teeth 3,
    4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 19, K, 21, 22,
    23, 24, 25, 26, 27, 28, T, 30

 All   probing depths are 3mm and under




                                                       25
    Localized Aggressive
            Periodontitis



   Questions…..

								
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