Oral Medicine

Papillon-Lefèvre syndrome-Successful treatment with a combinationof retinoid and concurrent systematic periodontai therapy:Case reports

Stephati Kressin*/Artnin Herforth*/Sabine Preis**/V. Wahn**/H. G. Lenard**

Papillon-Lefèvre syndrome is a rare autosomal-recessive congenital differentiation disorder:the external signs are hyperkeratosis of the palms and soles. Intraorally, the most salientmanifestations aie dystrophic periodontai problems that affect both the primary andpermanent dentitions and frequently lead to premature tooth loss. Two children were treatedwith acitretin 0.5 mg/kg of body weight per day from November 1992 to November 1993, andanother child since October 1993. Concurrently, the children receivedprofe.fsional oralhygiene care (scaling, root planing, and curettage). The combination of retinoid therapy andperiodontai treatment improved the dermatologie and periodontal conditions.(Quintessence Int 1995:26.795-803.)

Introduction

The symptom complex that includes hyperkeratosis ofthe internal surfaces ofthe hands and the soles ofthefeel; and concurrent serious periodontai problems inchildren and youths was described by Papillon andLefevre in 1924. Sitice then, more than 200 cases ofthis autosomal-recessive differentiation disorder havebeen reported. Its frequency is reported to be 1 to 5 permillion.' Apparently there is no gender preference.-

Changes ofthe skin are observed electron micro-scopically, with diminution of the tonofibrils. Alter-ations of the keratohyalin granules are found, as isacanthosis in the stratum spinosum. Additionai. ir-regular findings include a variety of disturbances ofthe

' Dcparlmeni of Period onto logy. Heinrich Heme University Dussel-dorf. Center of Dentistry, Düsseldorf. Germary.

*' Department of Pédiatrie Dentistry, Heinricli Heine University Düs-seldorf. Center of Dentistr>', Düsseldorf, Germany.

Reprint recjuests; Dr Stephan Kressln. Dorfplalz 6, D-12526 Berlin.Germany.

TTiis article was previously published in German as .Das Papillon-Lefèvre-Synd rom ; Erfolge bei der Therapie durch Kombination vonRetlnoidgabe und gleichzeitiger systematischer Parodontalbeliandlung"(Pamdoiilohgie 1994;4;305-314l.

immune system (in approximateiy 20%},--' ectopicintracranial calcifications (in about 6%), mental retar-dation, and acro-osteolysis.'

Intraorally. periodontai symptoms may arise soonafter the beginning of eruption ofthe primary teeth.The first signs are inflammatory changes ofthe gingiva.The teeth become mobile soon after eruption; toothmovement and tilting follow, and the teeth are lostspontaneously. The continuously progressive processof periodontai destruction affects the primary and thepermanent dentitions, so that the tbrmcr may be lost bythe age of 4 or 5 years and the latter by the age of 13 to15 years, depending on the severity of the disease."*Once the teeth are lost, the gingiva shows no furthersigns of periodontai alteration. It has been reponedthat the third molars are protected from the contin-uously progressing tooth ioss. '̂̂

Some reports have described a reciprocal relation-ship between the intensity of the kératoses andinflammatory episodes of tooth-supporting appara-tus.*''

It seems remarkable that the cutaneous changesrarely lead to consultation with a dermatologist, butthe early loss of teeth or extensive tooth mobility oftenis the reason for consuitation with a dentist.'

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Case reports

Case reports involving two siblings; aged 5 and 8years, are presented together with that of an unrelatedchild, aged 4 years. All three are children of healthy,consanguineous Turkish parents.'"

Case I

An 8-year-old boy had suffered gingival infiammationsince the eruption of his primaty teeth, which showedincreased mobility and began to fall otit during bisfourth year of life. Medical examination revealedtbalassemia minor. Results of neurologic and radiogra-pbic studies of the skeletal system (witb the exceptionof the jaws) and computerized tomography of the skullwere all noncontributory. Computer-assisted tomogra-phic studies of the maxilla and mandible indicatedwell-advanced vertical and horizontal bone résorptionTbe cusp tips of the second molars of the maxilla andmandible had erupted passively as a result of the boneloss, despite tbe absence of any root growth (Fig la).

Dermatologically, the patient showed palmoplantarhyperkeratosis (Fig lb).

Immunologie studies revealed no significant cbangesin surface markers (CD2, CD3, CD4, CD8, CD18,CDlla, CD3-CD56+), lymphocyte transformationtest with pbytohemagglutinin A, pokeweed mitogen,StaphylococcusaureusCowanl(SAC).OKT3(OrthoPharmaceuticai), and tetanus toxoid. Among normal¡mmunoglobulin in serum, immunoglobulin synthesisin vitro to SAC and SAC-i-II-2 was missing; in vivo itwas missing to pokeweed mitogen. The number ofpolymorpbonuclear granulocytes in blood and theoxygen production per 10* granulocytes were withinnormal limits.

Intraorally. the gingiva was chronically inflamed,edematous, swollen, and partially hyperplastic (Fig lc).Only two primary teeth (75 and 85) remained in themixed dentition. The permanent teeth had probingdepths of up to 10 mm and were mobile to grade II.The anterior teeth were decidedly protruded. Pusextruded from the pockets in response to pressure.Oral hygiene was entirely inadequate; the proximalspace Plaque Index was 100%," and the modifiedSulcular Bleeding Index also was lOOÏii.'̂

The boy was treated for 1 year (November 1992 toNovember 1993) with 0.5 mg/kg of body weight perday of acitretin. This therapy, including laboratory,clinical, and radiographie checkups, was toleratedwithout any problems.

Concurrently to this therapy, the patient wasprepared for systematic periodontal therapy. Twopreliminary appointments in which the periodontalstatus was recorded (Fig Id) and periodontitis markerorganisms were demonstrated through the DMD-Pathotek test, were completed. Evaluation ofthat test,however, revealed only a low to average number oforganisms (between 2 x 10' and 4 x lC*), Theorganisms found (Actinobacillus actinomycetes con-cotnitans, Porphyromonas ginglvalis, and Prevotelkintermedia) corresponded to those found in adultperiodontitis. The 10 permanent teeth were treatedthrough scaling, root planing, and curettage untilJanuary 1993; no antibiotic therapy was provided.

The first recall examination took place in April1993, when the patient reported a subjective feeling ofimprovement, particularly with respect to the maxillaryincisors. Tiie proximal Plaque Index was 82%; oniytwo teeth were free of plaque. The Suicular Bleedii^Index was 100%, Measurement of probing depthshowed improvement for five teeth, no change for one,and increased probing depths around four teeth (Figle). Orthodontic treatment, originally planned toretrude the tnaxillary incisors, was deemed inappro-priate at that time because of insufficient oral bygieneand significant mobiiity (grade II),

Acitretin therapy was interrupted in November1993 so that the course of the periodontal disease withand without the medicament could be observed. Atrecall appointments in September and December1993, oral hygiene conrinued to be poor. Progressiveperiodontal destruction was comparatively more rapidafter discontinuation of tbe medicament than before.Probing depths increased by I to 4 mm on seven teeth;no change was recorded on five other teeth. Threeteeth were atfected by increased mobility. Four monthsafter cessation of acitretin therapy, the periodontaicondition had worsened substantially (Fig IQ.

Case 2

In addition to palmoplantar hyperkeratosis (Fig 2a),both of this 5-year-old girl's lower legs showedsubpatellar hyperkeratosis (Fig 2b),

The child had a prematurely reduced (loss of allleeth from 64 to 74) and severely carious primarydentition (carious lesions on teeth 53, 63, 75, 73, 83,and S5). Tbe marginalgingiva was chronically inflamedand hyp erp la s tie in part. The mandibuiar centraiincisors and the 6-year molars were in eruption (Fig

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Figs la to If Case 1. Papillon-Lefèvre syndrome in an 8-year-old boy

Fig la (Leltj Panoramic view of the maxiila and mandibleat initial examination

Fig Ib (Seton'̂ Hyperkeratotic soies of the feet

Fig 1c Intraoral appearance

Fig Id Periodontal status at the beginning of treatment.

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Fig le Perjodontal status 3 months after initiation of treatment.

Fig If Panoramic radiograph ol tfiemaxilla and mandible 4 months aftercessation ot acitretin therapy.

2c). Her poor oral hygiene was reflected by a proximalPlaque Index of more than 80%) and a SulcularBleeding Index of 83%.

Radiographic findings, similar to those of her olderbrother, showed extensive horizontal and verticalbone loss in the maxilla and the mandible (Fig 2d).

Treatment, begun in September 1992, includedprofessional tooth cleaning and motivation of thechild, who was required to rinse twice daily at homewith Meridol solution. Acitretin therapy, providedfrom November 1992 to November 1993, was tole-rated well, according to clinical, laboratory, andradiographie follow-ups.

In January 1993, the child's oral hygiene haddecidedly improved; the proximal Plaque Index wasonly 10%, and the Sulcular Bleeding Index was 17%.Signs of inflammation were found around only onetooth. Recall examinations in April, September, andDecember 1993 indicated the situation to be stable;both index values were under 10%. The child was freeof complaints.

Case 3

A 4-year-old boy was referred by his physician fortreatment because of severe tooth tnobility. The child's

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Figs 2a to 2d Case 2. Papillon-Lefèvre syndrome in a 5-year-old girl (sister of boy in case 1).

Fig 2a Hyperkeratolic soles of the feet. Fig 2b Hyperkeratosis over the tibial tuberosity.

Fig 2c Initial intraorai appearance. Fig 2d Panoramic radiographie appearance ol the maxiilaand mandibie before treatment.

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Figs 3a to 3f Papi i ion-Lefevre syndrome in a 4-year-oid boy.

Fig 3a ÍHyperí<eratotic ínands. Fig 3b Hyperkeratolic elbows.

Fig 3c Hyperkeratotic knees. Fig 3d Hyperkeratotic soles of fhe feef.

extensive palmoplantar hyperkeratoses (Figs 3a to 3d)all had been treated as psoriasis. Medical examinationsrevealed no pathoiogic findings.

Intraoral examination revealed premature loss ofthe maxiiiary and mandibular incisors (teeth 52 to 62

and 72 to 82). Carious lesions were present on allremaining teeth. His marginal gingiva was reddenedand thickened (Fig 3e). The panoramic radiograph ofthe maxilia and mandible indicated notable horizontaland vertical bone loss (Fig 3f).

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Fig 3e Intraoral condition.

Fig 3f Panoramic radiograph oftbe maxilla and mandible.

In addition to acitretin therapy, oral bygiene ap-pointments were provided and restorations wereplaced to tbe extent that the severe tooth mobilitypermitted. Tbe brief period of treatment that haselapsed precludes any dependable conclusion aboutthe success of the combination therapy provided.

None of the parents gave permission for taking ofphotographs at the conclusion of treatment. For thatreason, it has been impossible to provide completedocumentarion of these three cases.

Discussion

These three case reports illustrate the chief characteris-tics of the PapiUon-Lefèvre syndrome; palmoplantarhyperkeratosis and periodontal disease.''''^""^ Addi-tional characteristics, such as intracranial calcifica-tion, psychomotor retardation, or aero-osteolysis,were not found.

Various authors have described immune systemdefects that are associated with a variety of fianctJonaldisturbances.''"'' Krekeler, in particular, pointed to

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defects of granulocyte adherence and chemotaxis-^"The extent to which immunologie disturbances can beconsidered the cause of recurrent inflatnmatory pro-cesses is not yet clean"^' The immunologie parame-ters ofthe 5-year-old giri and the 4-year-old boy werenot unusual; those ofthe 8-year-old boy show only afew nonspecific changes-

The chief problem of these patients related to theirperiodontal conditions. For the girl and the 4-year-oldboy. chronic gingivitis was the main concern; for the8-year-o!d boy, this condition was complicated bytooth mobility (lack of comfort during chewing andpain when brushing the teeth), and protrusion ofthemaxillary incisors. The latter condition made him anobject of ridicule at school.

Numerous views about treatment have been ex-pressed in the literature. D'Angelo et al" described a6.6-year-old boy in whom local therapy (extraction ofteeth with mobility grade III, scaling, root planing, andsubgingival irrigation with chlorhexidine) sufficed toreduce periodoncitis. Other authors beheve suchattempts at local therapy to hold liule promise.-'' ''^^

As an alternative, a series of reports have recom-mended retinoid therapy for retention of teeth-'•''*''̂ '̂ ''This type of therapy has found broad application indermatology since the early 1980s for the treatment ofkératoses. In long-term therapy, the bone toxicity ofthis preparation can lead to problems.'^"'' Distur-bances of growth in children, premature closure ofepiphyses, and traumatic fractures have been describedin case reports.̂ '̂̂ ^

Because long-term treatment should be avoided inchildren before epiphyseal closure,^" treatment waspaused after 12 months in these patients. The extremeworsening of the periodontal situation, which wasparticularly evident in the 8-year-old boy (see Eig If)about 4 months after cessation of the medicament,tends to support the argument in favor of continuationof the acitretin therapy.

Conclusion

The results in these three children have demonstratedthat eifective treatment of the Papillon-Lefèvre syn-drome is possible. The combination of retinoid andperiodontal therapy appears to be more effective thaneither alone. The cutaneous changes were influencedmore than the periodontal ones, because the latter canbe stabilized or retarded only with very good oralhygiene (strict recall).

Nothing can be said dependably about the long-term prognosis for the teeth from this study, because of

the relative short duration of therapy However, theresults observed in the 8-year-old boy indicate theneed for long-term treatment with acitretin m associa-tion with continuous dental care.

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21. Posteraro AF. Papillon-Lefèvre syndrome. NY State Dem J 1991;57-,49-50.

32. D'AngeloM.MargiottaV.AmmatumaP.SainmartanoF. Treatmentof preptibertal period o ntitjs, J Clin Periodontol I992i 19i2l4-219,

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therapy. J An AcadD

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