ELSEVIER Journal of the European Academy of Dermatology and Venereology

6 (1996) 57-61

Case report

Papillon-Lefevre syndrome in two sisters

V. De Giorgi *, L. Martini, F. Prignano, E. Donati, S. Moretti Clinica Dermatologica II, Universita degli Studi di Firenze, via della Pergola, 58, 50121 Florence, Italy

Abstract

Papillon-Lefevre syndrome is a rare disorder of keratinization inherited as an autosomal recessive trait. It is characterized by thickening of palms and soles, periodontopathia, tendency to pyogenic skin infections and sometimes mental impairment. The authors report Papillon-Lefevre syndrome in two sisters in whom the familial pedigree shows the autosomal recessive inheritance of the trait. Two other important disorders of keratinization transmitted by an autosomal recessive gene, Richner-Hanhart syndrome and Ma1 de Meleda, are excluded by clinical and metabolic criteria. Systemic therapy with etretinate and acitretin could not be performed because one of the patients has a hepatopathy and the other refuses the treatment. Application of local keratolytics is giving quite good results.

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

1. Introduction

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

* Corresponding author.

well as frequent pyogenic infections, have been reported in the literature [3-51. Regarding the adnexa there are no alterations of hair, while nails may present mild dystrophia. The frequency of the syndrome in the general population has been calculated at l-4 cases per 1 million inhabi- tants.

2. Case report

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

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

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58 V. De Giorgi et al. /J. Eur. Acad. Dematol. Venereal. 6 (1996) 57-61

Pedigree of family

Fig. 1. Two children of the parents’ cousins present the same disease.

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

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

The clinical examination revealed in both the presence of symmetric thickening of palms and soles (Figs. 2 and 3). The keratoderma involves mainly the anterior plantar surface, the heels and spreads towards the medial and plantar areas of both feet (Fig. 4). In one patient (MMAl), there is absence of premolar teeth at the inferior left hemidental arch and of the molars at the inferior right hemidental arch; while in the other (MMA2) all the molars are absent (Fig. 5).

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

Ophthalmological examination evidences neither alterations of vision nor cornea1 dystrophia.

3. Discussion

Keratoderma of palms and soles is found in a group of rare genodermatoses which typically present focal or widespread thickening of the corneous layer of hands and feet with other possi- ble abnormalities.

The most common criteria for classifying the syndrome is to separate it into two distinct groups, a dominant and a recessive one. For further, nosologic classification of each variety, one must consider, in addition to transmission modality and the morphologic aspects, the extent of in- volvement, degree of handicap, histopathology of the lesions, age of onset, and the association with neoplasias 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 symmetrically affected.

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

K De Giorgi et al. /J. Eur. Acad. Dermatol. Venereal. 6 (1996) 57-61

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 other keratodermas) because of the great similarity of the lesions both clinically and histopathologically and because of the difficulty in establishing the possible transmission modalities of the trait and the different morphologic varieties in families affected by the same syndrome. For example in Howel-Evans, Greither, Vohlwinkel Meleda and Papillon-Lefevre syndromes, the histopathology is not specific; in the epidermis there is essentially orthokeratotic hyperkeratosis, hypergranulosis, acanthosis and in the superficial dermis, some- times, a moderate perivascular infiltrate [7,8].

A pedigree, extended to four generations has confirmed the autosomal recessive transmission of the syndrome. Marriage between consan- guineous relatives and the long-term presence of the family in a relatively isolated geographic area and a poor r&o-cultural milieu enhance the possibility of sharing abnormal genes. These ele- ments allow us to exclude dominant forms.

In the forms of keratoderma of palms and soles by autosomal recessive inheritance we also include the Richner-Hanhart syndrome (or Ty- rosinemia type II), but in this form the hyperker- atosis is callous-like on pressure bearing areas of the soles, there is photophobia with cornea1 ul- cers and the mental impairment is very severe. Neither of our subjects presented cornea1 ulcers and there is no disturbance of tyrosine metabolism [9]. Ma1 de Meleda is excluded because both sisters presented significant dentition anomalies from birth [lo-131.

On the basis of the anamnestic data, clinical features, and histopathological findings we made a diagnosis of Papillon-Lefevre syndrome. It was not possible to administer acitretin and etreti- nate, because one of the two sisters presented hepatopathy and the other refused the treatment. Local therapy with keratolytics was administered in both, and is repeated periodically, with good results.

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

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

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