PapillonLefvre Syndrome

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Papillon-Lefèvre Syndrome

• Ashley L. Paulus, DDS
• Pediatric Dentistry Resident
• April 13, 2009

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Papillon-Lefèvre Syndrome

• First described by two French physicians,
  Papillon and Lefèvre, in 1924
• Prevalence of 1-4 cases per million persons
• Consanguinity between parents in 1/3 of cases
• Males and females are equally affected with no
  racial predominance
• Rare genetic disorder
• Autosomal recessive

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Papillon-Lefèvre Syndrome

• Rapid generalized periodontal destruction of
  alveolar bone (primary and secondary dentition)
• Palmar-plantar hyperkeratosis

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CTSC gene

• In humans, Cathepsin C is coded by the CTSC gene
• Located on chromosome 11q14-q21
• Encodes a cysteine-lysosomal protease known as
  dipeptidyl-peptidase I or Cathepsin C
• Appears to be a central coordinator for
  activation of many serine proteinases in
  immune/inflammatory cells

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Cathepsin C

• Found in PMN and leukocyte granules, important in
  protein degradation and proenzyme activation in
  PMNs and T-cells
• CTSC required for processing and activation of
  the T-lymphocyte granzymes A and B, the key
  agents of T cell-mediated cell killing
• Activator of the PMN-derived serine proteinases
  elastase, cathepin G, and proteinase 3
• These serine proteases are implicated in a wide
  variety of immune and inflammatory processes
• A lack of functional cathepsin C may be
  associated with a reduced host response against
  plaque bacteria

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Papillon-Lefèvre Syndrome

• The exact cause of periodontal disease in PLS has
  not been found but it has been attributed to
• Neutrophil defects
• Decreased neutrophil chemotaxis and phagocytosis
• Bacterial infection
• A. actinomycetemcomitans
• Natural killer cell defect
• Cytotoxicity

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Immunology

• Neutrophils create a barrier along the junctional
  epithelium and within the gingival crevice
• Neutrophils are the first line of defense against
  dental plaque microorganisms

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Neutrophils and Periodontal Disease

• Evidence that neutrophils are protective against
  periodontal destruction
• First, primary neutrophil or myeloid
  abnormalities have been associated with severe
  periodontal destruction.
• Second, otherwise healthy individuals with severe
  periodontal problems appear to have subtle
  defects in their neutrophils.
• Third, experimental neutropenia in animals leads
  to rapid periodontal infection.

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Papillon-Lefèvre Syndrome
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A. actinomycetemcomitans

• Facultatively anaerobic nonmotile gram-negative
  rod
• Produces virulence factors to promote its
  colonization and survival
• Leukotoxin is the prime virulence factor of A.a.
• Five distinct serotypes of A.a.
• Serotype B most commonly associated with diseased
  sites

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A. a. Leukotoxin

• 116-kDa pore-forming leukotoxin belonging to the
  repeat-in-toxins (RTX)
• Effects myeloid cells, such as PMNs and
  monocytes, and causes degranulation
• Cathepsin G and elastase from PMNs degrade this
  toxin extracellulary
• Cathepsin C activates the PMN-derived serine
  proteinases elastase and cathepsin G
• Decreases PMN ability to neutralize leukotoxin

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IgG2

• Alteration in immunoglobins present in PLS
• Elevated levels of salivary and serum IgG2
  antibody to A.a. in PLS
• Serum antibody IgG2 weak complement fixation
  activity and poor opsonization compared to other
  IgG subclasses
• IgG2 production dependant upon Th1

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PLS vs Haim-Munk Syndrome
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Haim-Munk Syndrome
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PLS vs Non-Syndromic Prepubertal Periodontitis
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PLS vs LJP
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Hyperkeratosis of the palms of the hands and
soles of the feet
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Dermatologic Treatment

• A multidisciplinary approach is important for the
  care of patients with PLS, skin manifestations
  are usually treated with emollients
• Salicylic acid and urea may be added to enhance
  their effects
• Oral retinoids including acitretin, etretinate,
  and isotretinoin are used in treatment of both
  the keratoderma and periodontitis associated with
  PLS

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Aggressive Periodontits in PLS
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Periodontal Treatment
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Periodontal Treatment

• Early treatment and compliance with the
  prevention program are the major determinants for
  preserving permanent teeth in young PLS patients
• By extracting all primary teeth and eradicating
  periodontal pathogens the patients adult teeth
  can erupt into a safe environment

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Pyogenic Liver Abscess in PLS
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References

• Ullbro C, Brown A, Twetman S. Preventive
  Periodontal Regimen in Papillon-Lefèvre Syndrome.
  Pediatric Dentistry 273, pages 226-231, 2005.
• Yang, H. W., Asikainen, S., Dogan, B., Suda, R.,
  Lai, C. H. Relationship of Actinobacillus
  actinomycetemcomitans serotype b to aggressive
  periodontitis frequency in pure cultured
  isolates. Journal of Periodontology, Taichung,
  Taiwan. www.pubmedcentral.nih.gov/articlerender.fc
  gi?artid88070
• Burne R, Lamont R, Lantz M, LeBlanc D. Oral
  Microbiology and Immunology. ASM Press.
  Washington, DC. 2006.
• Hart TC, Shapira L. Papillon-Lefèvre syndrome.
  Periodontol 2000. 1994 Oct688-100.
• Gorlin RJ, Sedano H, Anderson VE. The syndrome of
  palmar-plantar hyperkeratosis and premature
  periodontal destruction of the teeth. J Pediatr
  196465895-908.
• Rudiger S, Petersika G, Fleming F. Combined
  systemic and local antimicrobial therapy of
  periodontal disease in Papillon-Lefevre syndrome.
  A report of 4 cases. J Clin Periodontol199926847
  -54.
• Cury VF, Costa JE, Gomez RS, Boson WL, Loures CG,
  De ML. A Novel Mutation of the Cathepsin C Gene
  in Papillon-Lefevre syndrome. J Periodontol
  200273307-12.
• Lundgren, T., Parhar, R.S., Renvert, S., Tatakis,
  D.N. (2005). Impaired Cytotoxicity in
  Papillon-Lefevre Syndrome. JDR 84 414-417
• Moore SW, Millar AJW, Cywes S. Conservative
  initial treatment for liver abscesses in
  children. Br J Surg.1994 81 872 874
• Noack, B., Gorgens, H., Hoffmann, Th., Fanghanel,
  J., Kocher, Th., Eickholz, P., Schackert, H.K.
  (2004). Novel Mutations in the Cathepsin C Gene
  in Patients with Pre-pubertal Aggressive
  Periodontitis and Papillon-Lefevre Syndrome. JDR
  83 368-370