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

  • C. UllbroEmail author
  • S. Twetman


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.

Key words

Papillon-Lefèvre syndrome dental treatment cathepsin C 


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  1. 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.PubMedGoogle Scholar
  2. Agarwal S, Huang JP, Piesco NP, et al. Altered neutrophil function in localized juvenile periodontitis:intrinsic or induced? J Periodontal 1996;67:337–344.CrossRefGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. Baer PN, McDonald RE. Suggested mode of periodontal therapy for patients with Papillon-Lefèvre syndrome. Periodontal Case Rep 1981;3:10.PubMedGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.PubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.PubMedGoogle Scholar
  20. Firatli E, Tuzun B, Efeoglu A. Papillon-Lefèvre syndrome. Analysis of neutrophil chemotaxis. J Periodontol 1996:67:617–620.CrossRefPubMedGoogle Scholar
  21. Genco RJ, Zambon JJ, Christersson LA. The origin of periodontal infection. Adv Dent Res 1988;2:245–259.PubMedGoogle Scholar
  22. 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
  23. Glenwright HD, Rock WR Papillon-Lefèvre syndrome. A discussion of aetiology and a case report. Br Dent J 1990:168:27–29.CrossRefPubMedGoogle Scholar
  24. 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: 15:1–35CrossRefGoogle Scholar
  25. Hart TC, Shapira L. Papillon-Lefèvre syndrome. Periodontol 2000, 1994;6:88–100.CrossRefPubMedGoogle Scholar
  26. Hart TC. Genetic risk factors for early-onset periodontitis. J Periodontol 1996:67:355–366.CrossRefGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. 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.CrossRefGoogle Scholar
  31. Kinane DF, Attström R. Group A summary. J Clin Periodontol 2002:29:37–38.CrossRefGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. Lee MR, Wong LC, Fischer GO. Papillon-Lefèvre syndrome treated with acitretin. Australas J Dermatol 2005:46:199–201.CrossRefPubMedGoogle Scholar
  35. Liu R, Cao C, Meng H, Tang Z. Leukocyte functions in 2 cases of Papillon-Lefèvre syndrome. J Clin Periodontol 2000:27:69–73.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefPubMedGoogle Scholar
  39. Lundgren T, Renvert S. Periodontal treatment of patients with Papillon-Lefèvre syndrome. A 3-year follow-up. J Clin Periodontol 2004;31:933–938.CrossRefPubMedGoogle Scholar
  40. Lundgren T, Parhar RS, Renvert S, Tatakis DN. Impaired cytotoxicity in Papillon-Lefèvre syndrome. J Dent Res 2005:84:414–417.CrossRefPubMedGoogle Scholar
  41. 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.CrossRefPubMedGoogle Scholar
  42. Lyberg T. Immunological and metabolic studies in two siblings with Papillon-Lefèvre syndrome. J Periodontal Res 1982:17:563–568.CrossRefPubMedGoogle Scholar
  43. Marandian MH, N Foroozanfar, H Haghigat, et al. Papillon-Lefèvre syndrome and recurrent infections. Arch Fr Pediatr 1979:36:819–822.PubMedGoogle Scholar
  44. McCuire MJ, Lipsky PE, Thiele DL. Purification and characterization of dipeptidyl peptidase ¦ from human spleen. Arch Biochem Biophys 1992:295:280–288.CrossRefGoogle Scholar
  45. 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.CrossRefPubMedGoogle Scholar
  46. 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.CrossRefPubMedGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. 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.CrossRefPubMedGoogle Scholar
  49. Nuckols GH, Slavkin HC. Paths of glorious proteases. Nat Genet 1999:23:378–380.CrossRefGoogle Scholar
  50. 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.CrossRefPubMedGoogle Scholar
  51. 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.CrossRefPubMedGoogle Scholar
  52. 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.CrossRefPubMedGoogle Scholar
  53. 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.CrossRefPubMedGoogle Scholar
  54. 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.PubMedGoogle Scholar
  55. 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.CrossRefGoogle Scholar
  56. Preus HR. Treatment of rapidly destructive periodontitis in Papillon-Lefèvre syndrome. Laboratory and clinical observations. J Clin Periodontol 1988;15:639–643.CrossRefPubMedGoogle Scholar
  57. Rao NV, Rao GV, Hoidal JR. Human dipedtidyl-peptidase 1. Gene characterization, localization and expression. J Biol Chem 1997;272:10260–10265.CrossRefPubMedGoogle Scholar
  58. Ressa P. Keratoderma of the Papillon-Lefèvre type associated with diffuse hyperkeratosis follicularis. Arch Anat Microsc Exp 1970;59:195–197.Google Scholar
  59. 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.CrossRefPubMedGoogle Scholar
  60. Rosenthal SL. Periodontosis in a child resulting in exfoliation of the teeth. J Periodontal Res 1951;22:101–104.Google Scholar
  61. Ryan ME, Golub LM, Modulation of matrix metalloproteinase activities in periodontitis as a treatment strategy. Periodontol 2000, 2000;24:226–238.CrossRefPubMedGoogle Scholar
  62. 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.PubMedGoogle Scholar
  63. 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.CrossRefPubMedGoogle Scholar
  64. Tinanoff N, Tanzer JM, Kornman KS, Maderazo EG. Treatment of periodontal component of Papillon-Lefèvre syndrome. J Clin Periodontol 1986;13:6–10.CrossRefPubMedGoogle Scholar
  65. Tinanoff N, Tempro P, Maderazo EG. Dental treatment of Papillon-Lefèvre syndrome: 15-year follow-up. J Clin Periodontol 1995;22:609–612.CrossRefPubMedGoogle Scholar
  66. Ting M, Contreras A, Slots J. Herpesvirus in localized juvenile periodontitis. J Periodontal Res 2000;35:17–25.CrossRefPubMedGoogle Scholar
  67. 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.CrossRefPubMedGoogle Scholar
  68. 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.CrossRefPubMedGoogle Scholar
  69. 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
  70. 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.CrossRefPubMedGoogle Scholar
  71. 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.CrossRefPubMedGoogle Scholar
  72. Ullbro C, Brown A, Twetman S. Preventive periodontal regimen in Papillon-Lefèvre syndrome. Pediatr Dent 2005;27:226–232.PubMedGoogle Scholar
  73. 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.CrossRefGoogle Scholar
  74. Velazco CH, Coelho C, Salazar F, et al. Microbiological features of Papillon-Lefèvre syndrome periodontitis. J Clin Periodontal 1999;26:622–627.CrossRefGoogle Scholar
  75. 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.CrossRefPubMedGoogle Scholar
  76. 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.CrossRefPubMedGoogle Scholar
  77. 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.CrossRefPubMedGoogle Scholar

Copyright information

© European Archives of Paediatric Dentistry 2007

Authors and Affiliations

  1. 1.Institute for Postgraduate Dental EducationJönköpingSweden
  2. 2.Dept. OdontologyUmeå UniversityUmeåSweden
  3. 3.DeptCariology and Endodontics, School of Dentistry, Faculty of Health SciencesUniversity of CopenhagenCopenhagenDenmark

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