J Clin Periodontol 1995; 22: 609-412Printed in Denmark , All right.s reserved

Copyright © Munksgaard !995

Clinical penodontclogifISSN 0303-6979

Dental treatment ofPapillon-Lefevre syndrome:15-year follow-up

N.Tmanoff\ Paulette Tempro^ andEufronio G.IUladerazo^^School of Dental Medicine, University ofConnecticut Health Center, Farmington, CT06030 ^Department of Periodontoiogy, School ofDental Medicine, SUNY at Buffaio, 250 SquireHali, But^alo. NY 14214, ^Medical Researchi_aboratory, 26 Lafayette St,, Norwich, CT06360

Tinanoff N. Tempro P, Maderazo EG: Dental treatment of Papillon-Lefevresyndrome: 15-year follow-up. J Clin Periodontol 1995; 22: 609-612.© Mutiksgaard, 1995.

Abstract. A 9-year-old girl was initially treated for the periodotital component ofPapillon-Lefevre syndrome by extraction of all the patient's erupted teeth, afterunsuccessful clinical treatment with two different antibiotics. Follow-up dentalrecords at age 24 showed the patient to have generalized gingivitis and poor oralhygiene; however, no additional teeth were lost or mobile. Radiographically, thealveolar crests, lamina dura, and periodontal ligament spaces appeared normalfor a subject with missing teeth. Initially, the patient had depressed polymorpho-nuciear leukocyte (PMN) chemotaxis and adherence, as well as evidence of peri-odontai infection with Actinohacilius actinomycetemcomitans, (A.a.). The 6 and15-year follow-ups showed normal PMN function and no detectable A.a. The im-provement ofthe patient's PMN function was coincident with lack of detectionof certain periodontopathic bacteria. If the PMN dysfunction of PLS is second-ary to the infection, the reasons for the initiation of the disease still need to beclarified.

Key words: Papillon-Lefevre syndrome;ieui<ocyte function; actinobacillus; periodontitis

Accepted for publication 20 August 1994

In 1986. we reported a patient that hadbeen treated and followed for 8 yearsfor the periodontal component of Pa-pillon-Lefevre syndrome (PLS) (Tinan-off et al. 1986) This sydrome was firstdescribed in 1924 by Papilion and Le-fevre as a condition characterized byhyperkeratosis of the palms and solescombined with severe periodontitis,leading to premature loss of the pri-mary and permanent dentitions. Theetiology and pathogenesis of this dis-ease are not fully understood, but be-lieved to be inherited as an autosomalrecessive trait (Gorlin et al.l964). Theputative periodontopathic bacteria,Actinobacillus actinomycetemcomitans(A. a.), has been reportedly found inhigh numbers in the periodontalpockets (Preus 1988, Van Dyke et al.1984, Bimstein et al. 1990). In addition,there is evidence that some individualswith this disease have abnormal func-tion of polymorphonuclear leukoctyes(Djawari 1978, Van Dyke et al. 1984,

Tinanoff et al, 1986, Bimstein et a!,1990). The treatment ofthe periodontaldisease in PLS patients has usuallyfailed despite intensive therapy. Thepurpose of this report is to summarizea 15 year dental history regarding anapparently successful dental treatmentof a patient with PLS,

Case ReportInitial findings; patient at age 9 years

III February of 1977, a 9-year-oid His-panic female presented to the Univer-sity of Connecticut dental clinic with achief complaint o f sore gums and teethfalling out'. Her mother stated that thecondition was first noticed when herprimary teeth exfoliated at 5 years ofage. Besides a skin rash reported tohave developed at 6 months of agewhich persisted on the palms, knuckles,knees, elbows, and soles, and an allergyto penicillin, the patient's health historywas unremarkable. There was no fam-

ilial history of skin rash and prematureloss of teeth due to periodontitis.

Physical examination was unremark-able except for the integument which re-vealed hyperkeratosis of the palms, sol-es, elbows, knuckles and knees. Urinal-ysis, complete blood count, differentialblood count, serum calcium, phos-phate, and alkaline phosphatase valueswere normal, PMN function (Madera-zo & Ward 1978), however, showed thatchemotactic response to E. coli filtratewas depressed (patient-23.1 ±0,6 /im/h;normal control=33.8±1.5 //m/h. PMNadherence to nylon fibers was also re-duced, compared to norma! controls(patient's^55%; normal control^80%,whiie PMN bactericidal activity againstStaphylococcus aureus was normal (pa-tient^95% killing; normal contro!=96%),

The oral niucosa was within normallimits except for severe erythematousand edematous gingiva. No primaryteeth were present and one maxillary in-

610 Tinanoff et al.

cisor was missmg. The following per-manent teeth (FDI notation) were pres-ent: 16, 12, 11,21,26, 36, 33, 32, 31.41,42, 43, 46. 6 of these teeth had mobilityscores (Bergman et al. 1971) of +3.Purulent exudate could be expressedfrom the pockets of the molars and cen-tral incisors.

Radiographs reveaied that the al-veolar bone surrounding the mobileteeth iacked definable lamina dura andhad widened periodontal membranespaces. Extensive alveolar bone loss wasnoted around the mandibular centralincisors. Hand-wrist, lateral andpostero-anterior skull films were nor-mal. Subgingival plaque samples,plated aerobically and anaerobically onblood agar, revealed predominance ofCapnocytophaga F, nucleatum and E.corodens species. At that time (1977),we did not have adequate methods ofsamphng A. a.

Patient at age 24 years

The patient returned for replacement ofthe cast metal dentures which she hadworn for 9 years. The patient's medicalhistory continued to be not significant,although mild hyperkeratotic lesions onher hands, feet, elbows, and knees re-mained, Foilow-up blood studies, in-cluding CBC, differential blood count,leukocyte function tests, and fastingblood glucose, were performed and allwere normal. The leukocyte functiontest (Maderazo & Ward 1986) at thistime showed normal poiymorpho-nuclear leukocyte locomotory response,as determined by PMN + medium/sta-bilized act. serum (patient"s=^64,3 pmmigration; control 54.3 fim):, and nor-mal microbicidal function, as deter-mined by nitroblue tetrazolium reduc-tion (patient's-0,303; control-0,340).

The adherence assay was not done atthis time.

Follow-up dental records, includingfull-mouth radiographs, intraoralphotographs, and clinical indices, weretaken again. Due to the eruption of themandibulary third molars, 16 teeth werenow present instead of the 14 evidentin 1983. Radiographically, the alveolarcrests, iamina dura, and periodontalhgament spaces appeared normal for asubject with missing teeth. The maxil-lary third molars were congenitally ab-sent (Fig. !). The patient had general-ized gingivitis and poor oral hygiene.The mean plaque score (PLI) was 0.75.with 14 of 64 sites having a score of 2.The gingival index (GI) mean score was1.14 and 10 of 64 sites bled upon prob-ing (score of 2). 6 pocket depth meas-urements of each tooth showed that 3of the 96 sites had readings of 5 mm, 26

Initial treatment

Initial therapy consisted of 10 days ery-thromyein therapy for treatment of aperiodonta! abscess. After resolution ofthe periodontal abscess, the patient re-ceived a month's course of tetracycline,which was followed after a month of noantibiotics, with another month of ery-thromyein therapy. Clinical examin-ations during these periods showed noapparent change in gingival infiam-mation or tooth mobility. Due to theapparent failure of antibiotics and thepoor prognosis, a decision was made toextract al! the patient's erupted teeth.The aim of this procedure was to elim-inate the deep pockets that were the pri-mary ecologic niche of the implicatedperiodontal pathogens. Immediate den-tures were inserted the day after thesurgery and were followed by pro-visional, acrylic partial dentures whichallowed for the eruption of the remain-ing teeth.

Patient at age 15 years

When the patient was 15 years old. cast-metal partial dentures were constructed.Foilow-up records, including full-mouth radiographs, intra-oral photo-graphs, microbiologic samples, leuko-cyte function tests, and clinicai indiceson the 14 teeth that had erupted afterthe extraction phase of therapy al!showed normal findings (refer to Tinan-off et al. (1986) for complete descrip-tion).

Fig. 1, Posterior bitev^ing and periapical radiographs of patient at age 24 year. Alveolar crests,lamina dura, and periodonta! ligament spaces appeared normal for a subject with missingleeth. The maxillary third molars are congenitaily absent.

Treatment of Papillon-Lefevre syndrome 611

Table i. Summary of periodontal status, cultured hacteria, and leukocyte function at ages 9,15, aud 24

Age of Patient (years)

Periodontal status

Bacterial speciesCapnocytophagaE. nueleatumE, eorrodensA. actinomveetemeomitansBPBs

Leukocyte function

9

periodontitis

pos.

pos.*

n.d.

depressed

15

gingivitis

neg-neg.aeg-Tieg.

normal

24

gingivitis

•

pos.n ^ -neg-poi.

normal

*The microbiologic test was unavailable to us at this time; however, in 1977 the patient wasfound to have antihodies to A.a.n,d, = not done

had readings of 4 mm, and the remain-ing sites were 2 or 3 mm. No teeth weremobile,

Subgingival plaque was removedfrom mesial sites on teeth #17, 23, 27.38, 37, 44, 47, and 48 by means of onesterile paper point per site and thepoints were pooled into 1 ml prereducedRingers solution. Undiluted suspen-sions and 10"*, and lO"*" dilutions wereplated onto TSBV media containing ba-citracin and vancomycin, for the selec-tive recovery of A. a. These dilutionswere also plated on medium for theselective recovery of Capnocytophaga(CAP) (Rummens et al. 1985), and on5% sheep's blood agar supplementedwith 5,0 /Yg/ml of hemin and 0,5 //g/mlof menadione, TSBV and CAP mediawere both incubated in 5% CO2 andmoist air at 37°C for 3 to 5 days. Theblood agar plates were incubated in aCoy anaerobic chamber in 5% nitrogen,10% CO2 and air at 37°C for 7 to 10days, 25 colonies from each plate werepicked and characterized with respectto colony morphology. Gram stain ap-pearance and fermentation reaction inthe presence of carbohydrates using theMinitec differentiation system (BBLMicrobiology Systems, Cockeysville,MD), The results were positive for Cap-nocytophaga, F. nucleattim and blackpigmented bacteroides (BPBs); how-ever, the results were negative for E.corrodens, and A. a. Table 1 summarizesthe clinical, microbiological, and leuko-cyte function tests when the patient was9, 15, and 24 years of age.

Discussion

The failure of our initial treatment ofthis patient with PLS corroborates thehterature that conventional therapy isineffective in abating the periodontitis

of this syndrome. Due to the lack of im-provement in the patient's periodontalcondition with tetracycline and erythro-mycin antibiotic therapy, treatment wasfocused on the transient elimination ofthe patient's gingival pockets, the ecol-ogic niche of the suspected periodontalpathogens. The elimination of pockets,by extraction of all erupted teeth, mayhave inhibited the pathogen(s) fromspreading to the gingival crevices ofsucceeding teeth. The 15-year follow-upshowed minima! evidence of peri-odontitis affecting this subject's nowerupted maxillary canines, premolars,and 2nd and 3rd molars, despite the pa-tient's poor oral hygiene. The subgingi-val plaque sample, positive for Capno-cytophaga, F. nucleatum, and BPBs wascompatable with the diagnosis of gingi-vitis. The most imphcated bacteria inthis syndrome, A. a., was not detected.The follow-up tests of PMN chemotaxisand killing showed normal values. Inaddition, the patieht's risk for peri-odontitis may have been further re-duced because a time interval wouidhave allowed for development of im-mune responses to the periodontal anti-gens causing the initial bone loss.

At present, there are a few other re-ports of successful treatment of PLS, Inone case, treatment involved extractionof all teeth at age three, as well as a 10-day course of tetracycline (Baer 1989).The patient, at age 25 years, reportedlyhad norma! periodontal health. In an-other report, 2 patients with PLS whowere treated with continuous tetracy-cline for 2V2 years along with weeklyprofessional tooth cleaning and chlor-hexidine mouthrinse, were reported tohave an arrestment of disease (Preus1988), Progression of PLS was also notseen after 2 years in a subject that hadvital root submersion of 8 teeth thereby

eliminating all gingival sulci and peri-odontal pockets (Lu et al, 1987).

The apparent improvement of ourpatient's PMN function, and the paral-lel resolution ofthe infection of specificperiodontopathogens, supports thehypothesis that the PMN dysfunctionmay be due to bacteria or products ofbacteria in periodonta] pockets. Thereare other reports suggesting that defectsin PMN function in patients with peri-odontitis are caused, directly or in-directly, by specific periodontal bacteria(Shurin et al., 1979, Preus 1988, VanDyke 1986, Slots and Genco 1984), IfPMN dysfunction of PLS is secotidaryto the infection, the reasons for theinitiation ofthe disease still remains un-clear. Dyskeratosis of the gingivai epi-thelium (Lyberg 82), defective ce-mentum of the roots (Page & Baab1985), or other hereditary defects in-fiuencing the oral epithelial surface bar-rier need further exploration as to theirrole in the etiology of the periodontitisof PLS.

Aci<nowiedgement

The authors thank Drs. C. Kowalski,G, Ferretti, M, Cipes, J. Delaney; R,Haydenblit, C. Benitez and J. Castillofor treatment of this patient while Pedi-atric Dental residents.

Zusammenfassung

Zahnarztliehe Behandlung des Papillon-Lefev-re Syndroms: 15-Jahres-NachuntersuehungBei einem 9-jahrigcn Madcheii wurde nacherfolgloser Behandlung mit zwei uuterschied-liehen Antibiotika die parodontale Kompo-nente des Papillon-Lefevre Syndroms durehExtraktion aOer durchgebrochenen Zahneder Patieutin hehandelt. Die NachkontroUeder zahnar^tiichen Befunde im Alter von 24Jahren zeigte. daB die Patieutin eine generali-sierte Gingivitis und eine schkchte Mundhy-giene aufwies, Es waren jedoeh keine weite-ren Zahne verlorengegangen oder zeigten Be-wegiichkeit, Entsprechend einer Person mitfehlenden Zahnen erschienen rontgenolo-gisch der Liinbus aiveolaris. die Lamina duraParodontalspalt normal, Zu Begiiin hatte diePatientin eine reduzierte Chemotaxis undAdhareuz der polymorphkernigen Leukozy-ten (PMN) und auch offensichlich eiue paro-dontale Infektion mit Actinobacillus actino-mycetemeomitans (A.a.). Die Nachuntersu-chungeu nach seehs und fiirifzchn Jahrenzeigten normale PMN-Funktion und keinenNachweis von A,a. Die Verbesserung derPMN-Eunktion der Patieutin stand in Uber-einstimmung mit dem fehlenden Nachweisvon bestimmten parodontaipathogenen Bak-

612 Tinanoff el al

terien. Wenn die PMN-Fehlfunktion bei PLSsekundar zur Infektion auftritl, muC derGrund fur den Ausbruch dieser Erkrankungnoch geklart werden.

Resume

Traitement dentaire du syndrome de Papillon-Lefevre: suivi sur 15 anneesUne filletie a ete traitee inilialement a I'agede 9 ans pour l'eieinent parodonta] du syn-drome de Papiiion-Lefevre (PLS) par !"ex-traction de toutes ies dents ayant fait leureruption, apres I'echec d'un traitement clini-que avec prise de 2 antibiotiques differents.A I'age de 24 ans, les enregistrements dentai-res de !a surveillance en cours montraienlque la patiente avait une gingivite generaliseeet une mauvaise hygiene bucco-dentaire; ce-pendant, on n'observait ni la perte ni ia mo-bilite d'autres dents. A l'examen radiographi-que, les cretes alveolaires. la lamina dura etles espaces desmodontaux avaient une appa-rence normale pour un sujet chez qui desdents etaient absentes, Au debut, la patienteavait une dciicience du chimiotactisme et deI'adherenee des leucocytes polynucleaires(PMN), et presenlait les signes d'une infec-tion parodontaie par ActinobaeiUus actino-mycetemcomitans (A.a,). Aux controles apres6 annees et apres 15 annees, on constataitque la fonction des PMN etait normale etqu'-4.a. ne pouvait etre deeele, L'ameliora-tion de la fonction des PMN chez la patientecoincidaii avec I'absence de detection de pa-thogenes parodontaux certains. Si la dy-sfonction des PMN dans ie PLS est secondai-re a I'infection, il reste encore a elucider lesraisons de I'apparition de la maladie.

References

Baer, P, N, (1989) Preventing loss of teeth inpatients with Papillon-Lefevre syndrome.Journal of Pedodontics 13, 182-183,

Bergman, B,, Hugoson. A, & Olsson, C-A,(1971) Periodontal and prosthetic con-ditions in patients treated with removablepartial dentures and artificial crowns. AdaOdontologiea Scandanavia 29, 621-638,

Bimstein, E., Lustmann, J, Sela, M, N., Neri-ah. Z. B, & Soskoine, W, A, (1990) Peri-odontitis associated with Papiiion-Lefevresyndrome. Journal of Periodontologv 61,373-377.

Djawari. D, (1978) Deficient phagocyticfunction in Papillon-Lefevre syndrome.Dermatologiea 156. 189-192.

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Maderazo, E. G. & Ward, P, A. (1986)Leukocyte chemotaxis. In: Rose N,R.,Friedman, H, and Fahey, (eds.) Manual ofclinical laboratory tmmunoiogy. (AmericanSociety for Microbiology, Washington,DC, pp 290-294.

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Rtmiens, .1. L,, Frossepre, J,, De Gruyter, M,,Van de Vyver, H., Neyt, L., & Van Landu-yt, H, W (1985) The isolation of Capnocy-tophaga species with a new selective me-dium. Journal Clinical Microinology 22,375-378.

Shurin, S, B., Socransky, S. S., Sweeney, E, &Stossel, T R (1979) A neutrophil disorderinduced by Capnocytophaga, a dentalmicro-organism. New England Journal ofMedicine 301, 849-854,

Slots, J. & Genco, R, J, (3984) Black-pig-mented Baeteroides species, Capnocyto-phaga species, and ActinobaeiUus aetino-myeetemcomitans in human periodontaldisease: Virulence factors in colonization,survival, and tissue destruction. Journal ofDental Research 63, 412-42L

Tinanoff, N,. Tanzer, J, M,, Kornman, K.S. & Maderazo, E. G. (1986) Treatment ofthe periodonta! component of Papillon-Lefevre syndrome. Journal of Clinieal Peri-odontology 13, 6-10.

Van Dyke, T E., Taubman, M, A., Ebersole,J, L,, Haffajee. A, D,, Socransky. S. S,,Smith, D, J., SL Genco. R, J. (1984) ThePapillon-Lefevre Syndrome: neutrophildy.sfunction with severe periodontal dis-ease. Clinical Immunology and Immuno-patiwhgy 31, 419-429.

Address:

A , TinanoffDepartment of Pediatrie DentistrySchool of Dentat MedieineUniversity of Connecticut Health CenterFarmington. CT 06030-1610USATel: (203) 679-2933; fax (203) 679-4078