papillon-lefevre syndrome in two sisters

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  • ELSEVIERJournal of the European Academy of Dermatology and Venereology


    Case report

    Papillon-Lefevre syndrome in two sistersV. De Giorgi % L. Martini, F. Prignano, E. Donati, S. Moretti

    Clinica Dermatologica II. Universita degli Studi di Firenze, Via delta Pergola, 58, 50121 Florence. Italy


    PapiUon-Lcfevre syndrome is a rare disorder of keratinization inherited as an autosomal recessivetrait. It is characterized by thickening of pa]ms and soles, pcriodontopathia, tendency to pyogenic skininfections and sometimes mental impairment. The authors report Papillon-Lefevre syndrome in twosisters in whom the famiha] pedigree shows the autosoma! recessive inheritance of the trait. Two otherimportant disorders of keratinization transmitted by an autosoma] recessive gene, Richner-Hanhartsyndrome and Ma] de Meleda, are excluded by c]inical and metabolic criteria. Systemic therapy withetretinate and acitretin cou]d not be performed because one of the patients has a hepatopathy and theother refuses the treatment. Application of ]oca! kerato[ytics is giving quite good results.

    Keywords: Papillon-Lefevre syndrome; Keratoderma; Autosomal recessive disorder; Keratinization disor-ders; Palmo-plantar keratoderma

    L Introduction

    Papillon-Lefevre syndrome is a rare disorderof keratinization inherited as an autosomal reces-sive trait. It is characterized by keratoderma ofpalms and soles and periodontitis. The thickeingof palms and soles first appears during earlychildhood and can extend to other body areas,such as knees and c]bows. Periodontitis can leadto loss of teeth, both deciduous and permanent;caries, gingivitis and parodontitis may be present[1,2]. Cases presenting ectopic intracrania] calcifi-cations, acroosteolysis and mental impairment, as

    " Corresponding author.

    we]l as frequent pyogenic infections, have beenreported in the literature [3-5]. Regarding theadnexa there are no alterations of hair, whilenails may present mild dystrophia. The frequencyof the syndrome in the general population hasbeen calculated at 1-4 eases per 1 million inhabi-tants.

    2. Case report

    Two sisters aged 43 (MMAl) and 40 (MMA2)years o]d both presented palmar and plantar ker-atoderma.

    The family medical history shows that both theparents, the first degree cousins, and a younger

    0926-9959/9f,/$15.0() CO 1996 Elsevier Science B.V. All rights reservedSSDl 0926-9959(95)00098-4

  • 58 V. De Giorgi et al. /J. Eur. Acad Dermatol. Venereol. 6 (1996) 57-61


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    Fig. I. Two children of the parents' cousins present the same disease.

    sister are disease free. Two children of a cousinof the parents has the syndrome (Fig. 1).

    The keratoderma of palms and soles first ap-peared when the patients were almost one yearold, and during childhood they both sufferedfrom precocious caries and recurring gingivitis.

    The clinical examination revealed in both thepresence of symmetric thickening of palms andsoles (Figs. 2 and 3). The keratoderma involvesmainly the anterior plantar surface, the heels andspreads towards the medial and plantar areas ofboth feet (Fig. 4). In one patient (MMAl), thereis absence of premolar teeth at the inferior lefthemidental arch and of the molars at the inferiorright hemidental arch; while in the other (M]V1A2)all the molars are absent (Fig. 5).

    Histopathological examination of lesional skinshowed orthokeratotic hyperkeratosis, hypergran-ulosis and acanthosis. A lymphocytic perivascularinfiltrate was also detected (Fig. 6). Routine labo-ratory tests evidenced nothing of note; there wasabsence of tyrosine in serum as well as in urine.

    Ophthalmological examination evidences neitheralterations of vision nor corneal dystrophia.

    3. Discussion

    Keratoderma of palms and soles is found in agroup of rare genodermatoses which typicallypresent focal or widespread thickening of thecorneous layer of hands and feet with other possi-ble abnormalities.

    The most common criteria for classifying thesyndrome is to separate it into two distinct groups,a dominant and a recessive one. For further,nosologic classification of each variety, one mustconsider, in addition to transmission modalityand the morphologic aspects, the extent of in-volvement, degree of handicap, histopathology ofthe lesions, age of onset, and the association withneoplasias and other syndromes.

    It is not always possible to diagnose the spe-

    Fig. 2. Symmetric thickening of the palms.

    Fig. 3. The soles also are symmelrically affected.

    Fig. 4. The keratoderma involves mainly the anterior plantar surface.

  • V. De Giorgi et al. /J. Eur. Acad. Dermatol Venereol 6 (1996) 57-61 59

  • 60 V. De Giorgi et al. /J. Eur Acad. Dermatol. Venereol 6 (1996) 57-61

    Fig. 5. X-ray: absence of premolar teeth in one patient.

    cific syndrome (and to differentiate it from otherkeratodermas) because of the great similarity ofthe lesions both clinically and histopathologicallyand because of the difficulty in establishing thepossible transmission modalities of the trait andthe different morphologic varieties in familiesaffected by the same syndrome. For example inHowel-Evans, Greither, Vohlwinkel Meleda andPapillon-Lefevre syndromes, the histopathology isnot specific; in the epidermis there is essentiallyorthokeratotic hyperkeratosis, hypergranulosis,acanthosis and in the superficial dermis, some-times, a moderate perivascular infiltrate [7,8].

    A pedigree, extended to four generations hasconfirmed the autosomal recessive transmissionof the syndrome. Marriage between consan-guineous relatives and the long-term presence ofthe family in a relatively isolated geographic areaand a poor socio-cultural milieu enhance thepossibility of sharing abnormal genes. These ele-ments allow us to exclude dominant forms.

    In the forms of keratoderma of palms andsoles by autosomal recessive inheritance we alsoinclude the Richner-Hanhart syndrome (or Ty-rosinemia type II), but in this form the hyperker-atosis is callous-like on pressure bearing areas ofthe soles, there is photophobia with corneal ul-cers and the mental impairment is very severe.Neither of our subjects presented corneal ulcersand there is no disturbance of tyrosine metabolism[9]. Mai de Meleda is excluded because bothsisters presented significant dentition anomaliesfrom birth [10-13].

    On the basis of the anamnestic data, clinicalfeatures, and histopathological findings we madea diagnosis of Papillon-Lefevre syndrome. It wasnot possible to administer acitretin and etreti-nate, because one of the two sisters presentedhepatopathy and the other refused the treatment.Local therapy with keratolytics was administeredin both, and is repeated periodically, with goodresults.

  • V. De Giorgi et al /J. Eur Acad. Dermatol Venereol 6 (1996) 57-61 61

    Fig. 6. Histopathological picture showing orlhokeratotic hy-perkeratosis. hypergranulosis and acanthosis with a lympho-cytic perivascular infiltrate in the superficial dermis.

    References[I] Camacho F. BuMon P. The Papillon-Lefevre syndrome.

    Study of three siblings. EJD 1992:2:421-423.[2] Haneke E. The Papillon-Lefevre syndrome. Keratosis

    palmoplantaris with periodontopalhy. Report of a caseand review of the cases in the literature. Human Genet1979;51:l-35.

    [3] Trattner A. David M, Sandbank M et al. Papillon-Lefevresyndrome with acroosteolysis. J Am Acad Dermatol1991;24;835-838.

    [4] Bergman R. Friedman-Birnbaum R. Papillon-Lefevresyndrome: a study of the long term clinical course ofrecurrent pyogenic infections and the effects of etretinatetreatment. Br J Dermatol 1988;! 19:731-73().

    [S] Haini S. Munk J. Keratosis palmoplaniaris congenita.with periodontosis, arachnodactyly and a peculiar de-formity of the terminal phalanges. Br J Dermatol1965;77:42-54.

    [6] Nazzaro V, Blanchet-Bardon C. Mimoz C et al.Papillon-Lefevre syndrome. Arch Dennatol I98S:124:533-539.

    [7] Patrone P, Misciali C, Fanti PA. Cheralodcrmie palmo-plantari. G Ital Dermatol Venereol 199!:l2f,:19-22.

    [8] Poppa A. Santini R. Cheratodermia palmo plantarepunctata di Brauer-Buschke-Fischer. G Ital DermatolVenereol 1990:125:527-532.

    [9] Shimizu N, Masaaki I. Kaorn I et al. Richner-Hanhart ssyndrome. Arch dermatol 1990;126;I342-1346.

    IlO] Sybert VP, Dale BA. Halbrook KA. Palmar-plantar kera-toderma. J Am Acad Dermatol 1988;18:75-86.

    [II] Zemtsev A, Veitschegger M. Keratodermas. Int J Der-matol 1993;32:493-498.

    [12] Singh R. Nor M, Ghazali W, Atypical Papillon-Lefevresyndrome: keratosis palmoplantaris with periodontopa-thy. Inl J Dermatol 1993:32:450-452.

    UM Lestringant GG, Hadi SM, Qayed KI et al. Mai deMeleda: recessive transgressive palmoplantar kerato-derma with three unusual facultative features. Dermatol-ogy 1992;l84:78-82.