papillon-lefevre syndrome: clinical presentation and a brief review
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paand devastating periodontitis, affecting the primary aswell as the permanent dentition, attributed to a pointmutation of the cathepsin C gene.2-6
The syndrome is estimated to have frequency of 1-4pewiisthieo
patients with Papillon-Lefevre syndrome, and the rapidprogression of periodontitis results in severe loss ofalveolar bone.14-19 To preserve alveolar bone, earlyextraction of periodontally involved permanent teeth
Vol. 108 No. 1 July 2009
NDEditor million and 300 cases have been reported world-de.7 It seems that the incidence in the Saudi Arabiahigher compared with other parts of the world, ands may be attributed to cluster marriages (consanguin-us marriages).8,9 The onset of disease usually coin-es with the eruption of primary teeth. Boys and girlsequally affected, with no racial predominance.
Following eruption of primary teeth, the gingivaecome inflamed. This is generally followed by a rapidstruction of periodontium and most affected childrenperience premature loss of their primary teeth. Gin-
has been considered to be a mode of treatment.20-25For many years, clinicians have been aware of the
prosthetic problems posed by severely atrophic thinalveolar ridges, and this has constantly motivated cli-nicians to develop new methods of treatment.
In recent years, titanium implants have become animportant treatment alternative to replace missing teeth,and the present author was the first to experience suc-cessful use of them as a mode to rehabilitate patientswith Papillon-Lefevre syndrome.8
This paper presents the etiology and clinical features,and highlights different treatment modalities used topillon-Lefevre syndrome: clinical prreview
Parmanand J. Dhanrajani, BDS, MDS, MSc, MSSydney, AustraliaHCF DENTAL CENTRE
The Papillon-Lefevre syndrome (PLS) was first descessive disorder characterized by a diffuse palmoplanterriodontitis, affecting the primary as well as the permanengene. This paper presents a clinical presentation and a brg Oral Med Oral Pathol Oral Radiol Endod 2009;108:e
e Papillon-Lefevre syndrome (PLS) was first de-ibed by Papillon and Lefevre in 1924.1 It is antosomal recessive disorder characterized by a diffuselmoplanter hyperkeratosis and rapidly progressive
MEDICAL MANAGEMENT Aa seems to resume normal appearance after exfoli-on of the primary dentition.9 The aggressive inflam-tory periodontal process then repeats itself after the
l & Maxillofacial Surgeon.ceived for publication Sep 12, 2008; returned for revision Mar 7,9; accepted for publication Mar 9, 2009.9-2104/$ - see front matter009 Mosby, Inc. All rights reserved.
:10.1016/j.tripleo.2009.03.016tation and a brief
ACDS, FDSRCS, FFDRCSI,
by Papillon and Lefevre in 1924. It is an autosomaleratosis and rapidly progressive and devastatingition, attributed to a point mutation of the cathepsiniew of its etiology and treatment modalities. (Oral
ption of the permanent teeth, and in general all orst of the permanent dentition is lost during thenage years.10-13Conventional periodontal treatment usually fails in
PHARMACOLOGY UPDATErs: F. John Firriolo and Nelson I. Rhodusabilitate the oral cavity in patients with Papillon-fevre syndrome.
IOLOGY AND PATHOGENESISExact etiology and pathogenesis is unknown, butensive work during the last decade has revealedme important factors in the development of the dis-er. In recent years, three main factors are suggested
responsible for the initiation and progression of PLS.
OOOOEe2 Dhanrajani July 2009neticPapillon-Lefevre syndrome is an autosomal reces-e disorder. Recently, a few research groups haveorted that loss-of-function mutations of the lysoso-l protease cathepsin C gene are associated with PLSwell as related conditions.14-18 The cathepsin C geneexpressed in the epithelial regions commonly af-ted by PLS, such as palms, soles, knees, and kera-ized oral gingiva. The cathepsin C gene is alsopressed at high levels in various immune cells, in-ding polymorphonuclear leukocytes, macrophages,
d their precursors. This discovery will certainly leadbetter understanding of the signs and symptomsociated with PLS.3,4,20,21
munologicAnother important etiologic factor is an alteration of
host defense owing to decreased function of lym-ocytes,26 polymorphonuclear leucocytes, or mono-tes.27 The cathepsin C protein encoded by the CTSCne is a lysosomal cysteine proteinase that appears to betral coordinator for activation of many serine protein-s in immune/inflammatory cells, including the neutro-
il serine proteases (NPS) (cathepsin G [CTSG], elas-e, and proteinase 3).28 The inactivation of these NPSsy have multiple downstream effects that ultimatelyult in desregulation of the host immune response tocrobial infection. Ryu et al.26 recently proposed that thes of CTSC function and subsequent inactivity of neu-phil serine proteases may cause dysregulation of local-d polymorphonuclear leucocyte response in inflamedriodontal tissues, leading to the severe tissue destructionn in PLS.29
icrobialGram-negative microbial polysaccharides (LPS) arenerally recognized to be primary factors in the etiol-y of periodontitis, including PLS.19,22 Neutrophilction test showed reduced response to Staphylococ-
s spp. and Actinobacillus actinomycetecomitans.esence of virulent gram-negative anaerobic pathogensre found at the site of lesion (plaque/periodontal pock-), such as Bacteroides gingivalis, Capnocytophagas., spirochetes, and A. actinomycetemcomitans. Of the
thogens, A. actinomycetemcomitans constituted moren 50% of the total colony-forming units,20 and clin-l improvement followed its eradication. There is apothesis that periodontal herpes viruses together withthogenic bacteria, including A. actinomycetemcomi-s, and underlying host defense disorders, participatethe development of Papillon-Lefevre syndrome pe-dontitis.23,24There are also numerous virulence factors present,ch as leukotoxin, collagenase, endotoxin, epithelio-ins, and a fibroblast-inhibiting factor, suggestingt PLS is mediated bacteriologically and therefore
uld be treated to some improvement with antibiotics.24The subgingival plaque found in the periodontalckets of PLS patients resembles a typical periodon-s-associated microflora and has shown a predomi-nce of gram-negative anaerobic rods, including Por-yromonas gingivalis and spirochetes.28,30 Recentcrobiologic studies have revealed that periodontitisPLS patients may also be associated with A. actino-cetemcomitans.7,31,32Human keratinocytes in culture normally secrete gran-me B with antimicrobial activity that is able to protectainst invading pathogens. The activation of granzyme By thus provide protection against dermal inflamma-n.33,34 The failing activation of granzyme B in individ-ls with PLS might weaken the epithelial response to-rd bacterial infection and contribute to the individualpensity to develop gingival inflammation.
Defect of immune-mediated mechanisms, including re-ced lymphocyte response to pathogens, depression oflper-to-suppressor T-cell ratio, deficient monocyticction, elevation of serum immunoglobulin, and degen-tive changes of plasma cells,35 have been reported.The elevated antibody titers to A. actinomycetem-mitans support the microbial findings of the involve-nt of this bacteria in periodontopathy associated withS.36There are investigations carried out to check urinetabolism and serum vitamin C and zinc levels in PLSividuals in literature that were insignificant.
A dysplasia of the root cementum has been reportedPLS by Page and Baab,37 suggesting the possibilityabnormal deposition or maintenance of root cemen-, similar to that observed in less severe cases of
pophosphatasia. However, in that study the roots didt show any structural alterations that could accountthe severity of the periodontal lesions.38,39
It has been suggested that palmoplantar keratoses inS predispose to high incidences of malignant mela-ma. Nakajima et al.40 reported a 51-year-old Japa-se woman with PLS associated with recurrent malig-nt melanoma arising from hyperkeratotic cutaneousions. They also reported 4 other cases of malignantlanoma in PLS patients: Out of 4, 3 were Japanese,
d the authors suggested that this tendency might beributed to high frequency of acral lentiginous mela-ma in Japanese populations, in contrast to a lowquency of this subtype in caucasians.41
INICAL PRESENTATIONSThe onset of the cutaneous lesion of PLS (kerato-rma) may appear at birth or 1 to 2 months of age, butst commonly appears between the ages of 6 months
OOOOEVolume 108, Number 1 Dhanrajani e3d 4 years, coinciding with the eruption of primaryth.8The severity of keratoderma is variable, with theles being prominently more involved. The margins of
keratoderma are well defined and erythematous,quently extending to the thenar and hypothenar em-nces of the palm