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Review Paper: Dental Treatment for Patients with Papillon-Lefèvre Syndrome (PLS)

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Abstract

Aim: The aim of this article is to present a review of the most current literature regarding the aetiology of the periodontal disease that occurs in patients with Papillon-Lefèvre syndrome (PLS). It is also to encourage clinicians to adopt a treatment regime intending to save permanent teeth and alveolar bone in young patients with PLS. Review: The phenotypic expression of Papillon-Lefèvre syndrome is heterogeneous as regards the severity of the dermatological as well as the periodontal symptoms. The genetic defect is lack-of-function mutations of the gene encoding for cathepsin C, a lysosomal cysteine proteinase. The defect is associated with a severe reduction in the levels and activities of neutrophil-derived serine proteases (cathepsin G, elastase, Proteinase 3) and in the activation of granzyme B in natural killer cells. About 20% of patients with PLS experience infections besides the periodontal infection, although the patients are not known to be unusually susceptible to viral infections. The reason why many patients with PLS dodevelop periodontal inflammation is most likely due to the fact that the amount of aerobic and anaerobic pathogens in the periodontal pocket overpower a somewhat weakened innate immune response. Based on this literature review a standardised dental treatment protocol for patients with Papillon-Lefèvre syndrome is suggested. Conclusion: It is evident that by regularly reducing the periopathogenic flora in the oral cavity and by instigating a potent antibiotic therapy at an early stage of any potential infection, patients with PLS are not predestined to be edentulous in the permanent dentition.

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References

  • Adkison AM, Raptis SZ, Kelley DG, Pham CT. Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis. J Clin Invest 2002;109:363–371.

    PubMed  Google Scholar 

  • Agarwal S, Huang JP, Piesco NP, et al. Altered neutrophil function in localized juvenile periodontitis:intrinsic or induced? J Periodontal 1996;67:337–344.

    Article  Google Scholar 

  • Allende LM, Moreno A, de Unamuno P. A genetic study of cathepsin C gene in two families with Papillon-Lefèvre syndrome. Mol Genet Metab 2003;79:146–148.

    Article  PubMed  Google Scholar 

  • Almuneef M, Al Khenaizan S, Al Ajaji S, Al-Anazi A. Pyogenic liver abscess and Papillon-Lefèvre syndrome: not a rare association. Pediatrics 2003;111:85–88.

    Article  Google Scholar 

  • Baer PN, McDonald RE. Suggested mode of periodontal therapy for patients with Papillon-Lefèvre syndrome. Periodontal Case Rep 1981;3:10.

    PubMed  Google Scholar 

  • Berthou C, Michel L, Soulie A, et al. Investigation of granzyme B and Fas ligand proteins by human keratinocytes contributes to epidermal cell defense. J Immunol 1997;159:5293–5300.

    PubMed  Google Scholar 

  • Brown RS, Hays GL, Flaitz CM, et al. A possible late onset variation of Papillon-Lefèvre syndrome: report of 3 cases. J Periodontol 1993;64:379–386.

    Article  PubMed  Google Scholar 

  • Bullon P, Pascual A, Fernandez-Novoa MC, et al. Late onset Papillon-Lefèvre syndrome? A chromosomic, neutrophil function and microbiological study. J Clin Periodontol 1993;20:662–667.

    Article  PubMed  Google Scholar 

  • Cagli NA, Hakki SS, Dursun R, et al. Clinical, genetic, and biochemical findings in two siblings with Papillon-Lefèvre syndrome. J Periodontol 2005;76:2322–2329.

    Article  PubMed  Google Scholar 

  • Clerehugh V, Drucker DB, Seymore GJ, Bird PS. Microbiological and serological investigation of oral lesions in Papillon-Lefèvre syndrome. J Clin Pathol 1996;49:255–257.

    Article  PubMed  Google Scholar 

  • Czauderna P, Sznurkowska K, Korzon M, Roszkiewicz A, Stoba C. Association of inflammatory pseudotumor in the liver of Papillon-Lefèvre syndrome — case report. Eur J Pediatr Surg 1999:9:343–346.

    Article  PubMed  Google Scholar 

  • Cury VF, Costa JE, Gomez RS, et al. A novel mutation of the cathepsin C gene in Papillon-Lefèvre syndrome. J Periodontol 2002:73:307–312.

    Article  PubMed  Google Scholar 

  • De Haar SF, Jansen DC, Shoenmaker T, et al. Loss of function mutations in cathepsin C in two families with Papillon-Lefèvre syndrome are associated with deficiency of serine proteinases in PMNs. Hum Mutat 2004:23:524.

    Article  PubMed  Google Scholar 

  • De Haar SF, Tigchelaar-Gutter W, Everts V, Beertsen W. Structure of the periodontium in cathespin C-deficient mice. Eur J Oral Sci 2006;114:171–173.

    Article  PubMed  Google Scholar 

  • Del Fabbro M, Francetti L, Pizzoni L, Rozza R, Weinstein RL. Neutrophil physiology: role and mechanism of action in the immune response at gingival level. Minerva Stomatol 2000:49:227–248.

    PubMed  Google Scholar 

  • Dennison DK, Van Dyke TE. The acute inflammatory response and the role of phagocytic cells in periodontal health and disease. Periodontol 2000, 1997:14:54–78.

    Article  PubMed  Google Scholar 

  • De Vree H, Steenackers K, De Boever JA. Periodontal treatment of rapid progressive periodontitis in 2 siblings with Papillon-Lefèvre syndrome:15 years follow-up. J Clin Periodontol 2000:27:354–360.

    Article  PubMed  Google Scholar 

  • Eickholz P, Kugel B, Pohl S, Näher H, Staehle HJ. Combined mechanical and antibiotic periodontal therapy in a case of Papillon-Lefèvre syndrome. J Periodontol 2001:72:542–549.

    Article  PubMed  Google Scholar 

  • Eronat N, Ucar F, Kilinc G. Papillon-Lefèvre syndrome: treatment of two cases with a clinical microbiological and histopathological investigation. J Clin Pediatr Dent 1993:17:99–104.

    PubMed  Google Scholar 

  • Firatli E, Tuzun B, Efeoglu A. Papillon-Lefèvre syndrome. Analysis of neutrophil chemotaxis. J Periodontol 1996:67:617–620.

    Article  PubMed  Google Scholar 

  • Genco RJ, Zambon JJ, Christersson LA. The origin of periodontal infection. Adv Dent Res 1988;2:245–259.

    PubMed  Google Scholar 

  • Ghaffer KA, Zahran FM, Fahmy HM, Brown RS. Papillon-Lefèvre syndrome: neutrophil function in 15 cases from 4 families in Egypt. Oral surg Oral Med Oral Pathol Oral Radiol Endo 1999:33:320–325.

    Google Scholar 

  • Glenwright HD, Rock WR Papillon-Lefèvre syndrome. A discussion of aetiology and a case report. Br Dent J 1990:168:27–29.

    Article  PubMed  Google Scholar 

  • Haneke E. The Papillon-Lefévre syndrome: keratosis palmoplantaris with periodontopathy. Report of a case and review of the cases in the literature. Hum Genet 1979: 15:1–35

    Article  Google Scholar 

  • Hart TC, Shapira L. Papillon-Lefèvre syndrome. Periodontol 2000, 1994;6:88–100.

    Article  PubMed  Google Scholar 

  • Hart TC. Genetic risk factors for early-onset periodontitis. J Periodontol 1996:67:355–366.

    Article  Google Scholar 

  • Hart TC, Hart PS, Bowden DW, et al. E. Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome. J Med Genet 1999;36:881–887.

    PubMed  Google Scholar 

  • Hart PS, Zhang Y, Firatli E, et al. Identification of cathepsin C mutations in ethnically diverse Papillon-Lefèvre syndrome patients. J Med Genet 2000:37:927–932.

    Article  PubMed  Google Scholar 

  • Hart TC, Hart PS, Michalec MD, et al. Haim-Munk syndrome and Papillon-Lefèvre syndrome are allelic mutations in cathepsin C. J Med Genet 2000:37:88–94.

    Article  PubMed  Google Scholar 

  • Hewitt C, McGormick D, Linden G, et al. The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis. Human Mutat 2004:23:222–228.

    Article  Google Scholar 

  • Kinane DF, Attström R. Group A summary. J Clin Periodontol 2002:29:37–38.

    Article  Google Scholar 

  • Kleinfelder JW, Topoll HH, Preus HR, et al. Microbiological and immunohistological findings in a patient with Papillon-Lefèvre syndrome. J Clin Periodontol 1996:23:1032–1038.

    Article  PubMed  Google Scholar 

  • Kressin S, Herforth A, Preis S, Wahn V, Lenard HG. Papillon-Lefèvre syndrome — successful treatment with a combination of retinoid and concurrent systematic periodontal therapy: case reports. Quintessence Int 1995:26:795–803.

    PubMed  Google Scholar 

  • Lee MR, Wong LC, Fischer GO. Papillon-Lefèvre syndrome treated with acitretin. Australas J Dermatol 2005:46:199–201.

    Article  PubMed  Google Scholar 

  • Liu R, Cao C, Meng H, Tang Z. Leukocyte functions in 2 cases of Papillon-Lefèvre syndrome. J Clin Periodontol 2000:27:69–73.

    Article  PubMed  Google Scholar 

  • Lundgren T, Crossner CG, Twetman S, Ullbro C. Systemic retinoid medication and periodontal health in patients with Papillon-Lefèvre syndrome. J Clin Periodontol 1996:23:176–179.

    Article  PubMed  Google Scholar 

  • Lundgren T, Twetman S, Johansson I, Crossner CG, Birkhed D. Saliva composition in children and young adults with Papillon-Lefèvre syndrome. J Clin Periodontol 1996:23:1068–1072.

    Article  PubMed  Google Scholar 

  • Lundgren T, Renvert S, Papapanou PN, Dahlén G. Subgingival microbial profile of Papillon-Lefèvre patients assessed by DNA-probes. J Clin Periodontol 1998:25:624–629.

    Article  PubMed  Google Scholar 

  • Lundgren T, Renvert S. Periodontal treatment of patients with Papillon-Lefèvre syndrome. A 3-year follow-up. J Clin Periodontol 2004;31:933–938.

    Article  PubMed  Google Scholar 

  • Lundgren T, Parhar RS, Renvert S, Tatakis DN. Impaired cytotoxicity in Papillon-Lefèvre syndrome. J Dent Res 2005:84:414–417.

    Article  PubMed  Google Scholar 

  • Lux CJ, Kugel B, Komposch G, Pohl S, Eickholz P. Orthodontic treatment in a patient with Papillon-Lefèvre syndrome. J Periodontol 2005 Apr:76(4):642–50.

    Article  PubMed  Google Scholar 

  • Lyberg T. Immunological and metabolic studies in two siblings with Papillon-Lefèvre syndrome. J Periodontal Res 1982:17:563–568.

    Article  PubMed  Google Scholar 

  • Marandian MH, N Foroozanfar, H Haghigat, et al. Papillon-Lefèvre syndrome and recurrent infections. Arch Fr Pediatr 1979:36:819–822.

    PubMed  Google Scholar 

  • McCuire MJ, Lipsky PE, Thiele DL. Purification and characterization of dipeptidyl peptidase ¦ from human spleen. Arch Biochem Biophys 1992:295:280–288.

    Article  Google Scholar 

  • Meade JL, de Wynter EA, Brett R et al. A family with Papillon-Lefèvre syndrome reveals a requirement for cathepsin C in granzyme B activation and NK cell cytolytic activity. Blood 2006:107:3665–3668.

    Article  PubMed  Google Scholar 

  • Murphy G, Atkinson S, Ward R, Gavrilovic J, Reynolds JJ. The role of plasminogen activators in the regulation of connective tissue metalloproteinases. Ann NY Acad Sci 1992:667:1–12.

    Article  PubMed  Google Scholar 

  • Nakano A, Nomura K, Nakano H, et al. Papillon-Lefèvre syndrome: mutations and polymorphisms in the cathepsin C gene. J Invest Dermatol 2001:116:339–343.

    Article  PubMed  Google Scholar 

  • Noack B, Gorgens H, Hoffman T,et al. Novel mutations in the cathepsin C gene in patients with pre-pubertal aggressive periodontitis and Papillon-Lefèvre syndrome. J Dent Res 2004:83:368–370.

    Article  PubMed  Google Scholar 

  • Nuckols GH, Slavkin HC. Paths of glorious proteases. Nat Genet 1999:23:378–380.

    Article  Google Scholar 

  • Oguzkurt R, Tanyel FC, Buyukpamukcu N, Hicsonmez A. Increased risk of pyogenic liver abscess in children with Papillon-Lefèvre syndrome. J Pediatr. Surg 1996:31:955–956.

    Article  PubMed  Google Scholar 

  • Page RC, Offenbacher S, Schroeder HE, Seymore GJ, Kornman KS. Advances in the pathogenesis of periodontitis: summary of development, clinical implications and future directions. Periodontol 2000, 1997;14:216–248.

    Article  PubMed  Google Scholar 

  • Pavicic MJ, van Winkelhoff AJ, Dougue NH, Steures RW, de Graaf J. Microbiological and clinical effects of metronidazole and amoxicillin in Actinobacillus actinomycetemcomitans-associated periodontitis. A 2-year evaluation. J Clin Periodontol 1994:21:107–112.

    Article  PubMed  Google Scholar 

  • Pham CT, Ley TJ. Dipeptidyl peptidase ¦ is required for the processing and activation of granzymes A and B in vivo. Proc Natl Acad Sci USA 1999:96:8627–8632.

    Article  PubMed  Google Scholar 

  • Pham CT, Ivanovich JL, Raptis SZ, Zehnbauer B, Ley TJ. Papillon-Lefèvre syndrome: correlating the molecular, cellular, and clinical consequences of cathepsin C/dipeptidyl peptidase ¦ deficiency in humans. J Immunol 2004;173:7277–7281.

    PubMed  Google Scholar 

  • Pilger U, Hennies HC, Truschnegg A, Aberer E. Late-onset Papillon-Lefèvre syndrome without alteration of the cathepsin C gene. J Am Acad Dermatol 2003;49:240–243.

    Article  Google Scholar 

  • Preus HR. Treatment of rapidly destructive periodontitis in Papillon-Lefèvre syndrome. Laboratory and clinical observations. J Clin Periodontol 1988;15:639–643.

    Article  PubMed  Google Scholar 

  • Rao NV, Rao GV, Hoidal JR. Human dipedtidyl-peptidase 1. Gene characterization, localization and expression. J Biol Chem 1997;272:10260–10265.

    Article  PubMed  Google Scholar 

  • Ressa P. Keratoderma of the Papillon-Lefèvre type associated with diffuse hyperkeratosis follicularis. Arch Anat Microsc Exp 1970;59:195–197.

    Google Scholar 

  • Robertson KL, Drucker DB, James J, Blinkhorn AS, Hamlet S, Bird PS. A microbiological study of Papillon-Lefèvre syndrome in two patients. J Clin Pathol 2001;54:371–376.

    Article  PubMed  Google Scholar 

  • Rosenthal SL. Periodontosis in a child resulting in exfoliation of the teeth. J Periodontal Res 1951;22:101–104.

    Google Scholar 

  • Ryan ME, Golub LM, Modulation of matrix metalloproteinase activities in periodontitis as a treatment strategy. Periodontol 2000, 2000;24:226–238.

    Article  PubMed  Google Scholar 

  • Rüdiger S, Petersilka G, Flemmig TF. Combined systemic and local antimicrobial therapy of periodontal disease in Papillon-Lefèvre syndrome. A report of 4 cases. J Clin Periodontol 1999;26:847–854.

    PubMed  Google Scholar 

  • Selvaraju V, Markandaya M, Prasad PV, et al. Mutation analysis of the cathepsin C gene in Indian families with Papillon-Lefèvre syndrome. BMC Med Genet 2003;4:5.

    Article  PubMed  Google Scholar 

  • Tinanoff N, Tanzer JM, Kornman KS, Maderazo EG. Treatment of periodontal component of Papillon-Lefèvre syndrome. J Clin Periodontol 1986;13:6–10.

    Article  PubMed  Google Scholar 

  • Tinanoff N, Tempro P, Maderazo EG. Dental treatment of Papillon-Lefèvre syndrome: 15-year follow-up. J Clin Periodontol 1995;22:609–612.

    Article  PubMed  Google Scholar 

  • Ting M, Contreras A, Slots J. Herpesvirus in localized juvenile periodontitis. J Periodontal Res 2000;35:17–25.

    Article  PubMed  Google Scholar 

  • Toomes C, James J, Wood AJ, et al. Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Nat Genet 1999;23:421–424.

    Article  PubMed  Google Scholar 

  • Turk D, Janjic V, Stern I, et al. Structure of human dipeptidyl peptidase ¦ (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. EMBO J 2001;20:6570–6582.

    Article  PubMed  Google Scholar 

  • Ullbro C, Lundgren T, Crossner C-G. Papillon-Lefèvre syndrome: a challenge to the dental team. Abstract, Swed Dent J 1997;6:227.

    Google Scholar 

  • Ullbro C, Crossner CG, Lundgren T, Stalblad PA, Renvert S. Osseointegrated implants in a patient with Papillon-Lefèvre syndrome. A 41/2-year follow-up. J Clin Periodontol 2000;27:951–954.

    Article  PubMed  Google Scholar 

  • Ullbro C, Crossner C-G, Nederfors T, Alfadley A, Thestrup-Pedersen K. Dermatological and oral findings in a cohort of 47 patients with Papillon-Lefèvre syndrome. J Am Acad Dermatol 2003;48:345–351.

    Article  PubMed  Google Scholar 

  • Ullbro C, Brown A, Twetman S. Preventive periodontal regimen in Papillon-Lefèvre syndrome. Pediatr Dent 2005;27:226–232.

    PubMed  Google Scholar 

  • Waraaswapati N, Lertsirivorakul J, Nagasawa T, Kawashima Y, Ishikawa I. Papillon-Lefèvre syndrome: serum immunoglobulin G (IgG) subclass antibody response to periodontopathic bacteria. A case report. J Periodontol 2001; 72:1747–1754.

    Article  Google Scholar 

  • Velazco CH, Coelho C, Salazar F, et al. Microbiological features of Papillon-Lefèvre syndrome periodontitis. J Clin Periodontal 1999;26:622–627.

    Article  Google Scholar 

  • Wiebe CB, Hakkinen L, Putnins EE, Walsh P, Larjava HS. Successful periodontal maintenance of a case with Papillon-Lefèvre syndrome: 12 year follow-up and review of the literature. J Periodontol 2001; 72:824–830.

    Article  PubMed  Google Scholar 

  • Wolters PJ, Pham CT, Muilenburg DJ, Ley TJ, Caughey GH. Dipeptidyl peptidase ¦ is essential for activation of mast cell chymases, but not tryptases, in mice. J Biol Chem 2001;276:18551–18556.

    Article  PubMed  Google Scholar 

  • Woo I, Brunner DP, Yamashita DD, Le BT. Dental implants in a young patient with Papillon-Lefèvre syndrome: a case report. Implant Dent 2003;12:140–144.

    Article  PubMed  Google Scholar 

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  1. Institute for Postgraduate Dental Education, Jönköping, Sweden

    C. Ullbro

  2. Dept. Odontology, Umeå University, Umeå, Sweden

    C. Ullbro

  3. DeptCariology and Endodontics, School of Dentistry, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    S. Twetman

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Ullbro, C., Twetman, S. Review Paper: Dental Treatment for Patients with Papillon-Lefèvre Syndrome (PLS). Eur Arch Paediatr Dent 8 (Suppl 1), 4–11 (2007). https://doi.org/10.1007/BF03262602

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