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Year : 2015  |  Volume : 7  |  Issue : 1  |  Page : 54-58

Papillon-Lefèvre syndrome: Clinical presentation and literature review

1 Department of Oral and Maxillofacial Surgery and Oral Pathology, College of Health Sciences, Obafemi Awolow University, Ile-Ife, Nigeria
2 Department of Surgery, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria

Date of Web Publication20-May-2015

Correspondence Address:
Dr. A O Taiwo
Department of Surgery, College of Health Sciences, Usmanu Danfodiyo University, Sokoto
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-8844.157393

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Background: Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive genodermatosis characterized by a diffused palmoplantar hyperkeratosis and severe early-onset periodontitis. Although the exact pathogenesis of this syndrome is still unknown, however, it has been linked to mutations in the cathepsin C gene. Case report: This paper is a clinical presentation of a 12-year-old male with severe periodontitis and characteristic palmoplantar hyperkeratosis diagnosed as PLS. Conclusion: An early diagnosis of the syndrome can help preserve the teeth by the early institution of treatment, using a multidisciplinary approach. Thereby, sparing the patients increase the risk of social, psychological, and economical stigma. Owing to the vast degree of periodontal breakdown involved at such an early age. Incidentally, the dentist is might often be the first to encounter such patients.

Keywords: Cathepsin C gene, genodermatosis, palmoplantar hyperkeratosis periodontitis, Papillon-Lefèvre syndrome

How to cite this article:
Soyele O O, Taiwo A O. Papillon-Lefèvre syndrome: Clinical presentation and literature review. J Orofac Sci 2015;7:54-8

How to cite this URL:
Soyele O O, Taiwo A O. Papillon-Lefèvre syndrome: Clinical presentation and literature review. J Orofac Sci [serial online] 2015 [cited 2023 Jan 27];7:54-8. Available from:

  Introduction Top

Papillon-Lefèvre syndrome (PLS) is a rare, autosomal recessive heterogeneous disorder, which was first described in the literature by two French physicians Papillon and Lefevre in 1924. [1] PLS is characterized by palmoplantar hyperkeratosis, early loss of primary and permanent teeth, and associated calcification of the dura mater. [2],[3] The incidence rate of PLS is between 1 and 4r persons/million without racial or sexual predilection, although the incidence of 6.5 cases/million was discovered in the Slovenian population which is substantially superior to that mentioned in the literature [4] and greater frequency of occurrence in the consanguineous offspring has been determined in about 20-40% of patients with this condition. [3] This keratinization disorder is characterized by palmoplantar hyperkeratosis, premature exfoliation of both primary and permanent dentition, and early onset aggressive periodontitis. Associated features may include intra-cranial calcifications, susceptibility to bacterial infections and mental retardation. [4] Other regions often affected by keratosis include the dorsal surface of hands and feet, knees, elbows, dorsal eyelids, cheeks, thighs, labial commissures, and external malleolus although with significant variation. [3],[5]

The exact etiology of PLS is obscured, and factors such as immunologic, inflammatory and virulent pathogens has been linked to this syndrome, however, the molecular basis responsible for this condition has been elucidated. [5] Researchers from various studies have discovered a genetic mutation in cathepsin-C (CTSC) gene which encodes a cysteine-lysosomal protease known as dipeptidyl peptidase I or CTSC, removing dipeptides from the amino-terminus of protein substrates and mainly plays an immune and inflammatory role. [5],[6] Variation in the clinical presentation of PLS has been observed, however, cutaneous and oral lesions are characteristics. [5] PLS usually manifests itself between the ages of 6 months to 4 years, coinciding with the eruption of primary teeth and leads to premature loss of both primary and permanent dentitions. [7] The cutaneous lesions presenting as sharply demarcated erythematous keratotic plaques on the palms and soles, with extension to the dorsal surfaces are often manifested simultaneously with the intra-oral presentations. These cutaneous regions are more severely affected than the others with erythematous presentation always preceding the hyperkeratosis. [7],[8] Histopathologic findings are nonspecific, however, hyperkeratosis with irregular parakeratosis, acanthosis, and a moderate chronic inflammatory perivascular infiltrate predominantly lymphocytes and plasma cells have been described. [9] The management of this condition requires a multidisciplinary approach involving the dermatologist and dentist. Oral lesions often respond to classic periodontal treatment if instituted early. [10],[11]

To the best of our knowledge, there is a single published report [12] of a patient with this syndrome from Nigeria or Africa in the literature. Hence, we report a case of PLS from our center in North-Western Nigeria with characteristic skin and oral lesions.

  Case Report Top

A 12-year-old male patient presented to the oral diagnosis unit of the dental department of our hospital with the chief complaint of premature exfoliation of teeth which commenced with deciduous dentition since the patient was 4-year-old and loosening of the remaining permanent teeth. Past medical history showed a concurrent pyogenic infection of the skin which was reportedly managed with a traditional topical agent which proved unsuccessful. Past dental history revealed it was the patient first ever visit to the hospital as well as to a dental clinic on account of the present scenario and that there was severe mobility of the deciduous teeth prior to exfoliation of each tooth about 5-6 months after complete eruption the trend which was similarly observed in the permanent dentition. Patient had stopped brushing because of teeth mobility hence associated odynophagia, pain, gingival swelling, and occasional bleeding. Patient is from the rural area, father is a nomadic with low socioeconomic background and a polygamous family of two wives, he is the third of six surviving children in which four had died all of whom were said to have experienced similar skin and oral lesions.

On clinical examination, the patient presented with a senile facial appearance. There was symmetrical, well-demarcated keratotic and confluent plaques involving the skin of the dorsal and plantar surfaces of the palms of hands and soles of feet bilaterally with consequent difficulty in walking due to plantar lesions on the feet [Figure 1] and [Figure 2]. This was noticed at about the age of 2 years and observed to be more severe during cold weather. The skin was dry and rough on palpation, well-circumscribed, psoriasiform, erythematous, scaly plaques were also present on the elbows and knees bilaterally; however, the hair and the nails appear clinically normal. Intraoral examination revealed that the two central and lateral incisors, first and second premolars and first molar on both quadrant of the maxilla, as well as central and lateral incisors on both quadrant of the mandible were missing. The mobile teeth include canine on both quadrants of the maxilla, second premolar on the upper left, canine on the mandibular right quadrant and both premolars on the mandibular left quadrant. In addition, first and second premolars on the lower right, canine and first molar on the lower left were also mobile. They all exhibited Grade 3 mobility due to extensive alveolar bone loss and severe periodontal breakdown subsequent to inflammatory destruction of gingival, alveolar bone loss and deep periodontal pocket; gingival in relation to the existing permanent teeth were red, soft and edematous with associated recession, deep periodontal pocket and bleeding on probing [Figure 3]. The overlying mucous membrane including the edentulous area appeared clinically healthy. Routine clinical investigations such as full blood count and liver ultrasound were all normal. Based on medical and dental findings, the diagnosis of PLS was made. Patient was referred to our dermatology unit for the management of the cutaneous lesion. Scaling and polishing were instituted, however, the entire patient's remaining teeth were observed to be floating given a sense of very poor prognosis hence complete extraction and treatment options for prosthodontic rehabilitation were discussed. Considering the patient's age and poor socioeconomic status, a set of complete dentures was planned for now with possible dental implant in future however, patient did not report for the outlined management of the oral condition and efforts at locating the patients' residence proved abortive.
Figure 1: Keratotic plaques on the dorsal skin surface of fingers with extension to the palms of the hands . Bilateral palmar hyperkeratosis of the hands in the 12 year old patient with Papillon-Lefèvre syndrome (PLS)

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Figure 2: Keratotic plaques involving the entire dorsal surface of the feet, with extension of the keratotic plaques over the plantar aspect of the feet. The skin appears dry, scaly and rough. Bilateral plantar hyperkeratosis of the feet in the 12 year old patient with Papillon-Lefèvre syndrome (PLS)

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Figure 3: Intraoral photograph showing missing permanent teeth with alveolar resorption in the anterior region of the upper and lower arch as a result of aggressive periodontitis in a 12 year old patient with Papillon-Lefèvre syndrome (PLS)

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  Discussion Top

Papillon-Lefèvre syndrome is an autosomal recessive inherited disorder whereby parents of the affected patient, possess the autosomal gene for this syndrome to manifest in their offspring however the parents are clinically healthy, with no family history of the disorder. [13] When 2 such carriers mate, there is a 25% chance of producing affected offspring [8],[10] as observed in this case as the parents history confirmed similar presentation in some of the siblings as well.

Papillon-Lefèvre syndrome has a reported prevalence of 1-4 cases per million. [3] The disorder is characterized by diffuse palmoplantar keratoderma and rapidly progressing periodontitis leading to premature loss of both deciduous and permanent teeth. A third component of dural calcifications has also been reported by Gorlin et al. [12] Almuneef et al. [11] recognize pyogenic liver abscess to be a fairly frequent complication of PLS. Dural calcification could not be ascertained owing to nonaffordability of computed tomography scan and also no abnormal liver ultrasonographic finding was detected in this present case.

The characteristic dermatological lesions of symmetric palmoplantar keratosis of hands and feet including the dorsal surfaces of the extremities and others (elbows and knees) was first noticed at about the age of 2 years consistent with most reports in the literature. [1],[5],[7] These lesions have been reported to be more severe during cold weather as also evidenced in this case. [7],[8] There was a positive history of manifestation of recurrent pyogenic skin infections since early childhood, a finding which was also demonstrated by Subramaniam et al. [15] and could be attributed to the increased susceptibility to bacterial infections in these patients. Furthermore, the application of traditional ointment could also predispose the patient to recurrent skin infection and perhaps aggravated it.

The intraoral presentation of severe generalized aggressive periodontitis as early as 3-4 years of age following the complete eruption of the deciduous teeth was observed in this case and concurred with observation in reported cases in the literature. The deciduous teeth develop normally, but their eruption is associated with severe gingival inflammation and subsequent periodontal destruction leading to a premature loss of the primary dentition, this trend was similarly noticed in this report. [2],[5],[7],[8] A temporary period of healthy gingival tissue was followed by another phase of destructive periodontitis once the permanent teeth erupt as reported here with resultant potential toward partial or complete edentulous status in their early teens, and this is probably the complication in this patient which is the trend in most studies. [1],[3],[5],[7]

The exact etiopathogenesis of PLS is relatively unknown, however, Singh et al. [16] and Hattab et al. [17] attributed its etiology into three main factors which are reportedly responsible for the initiation and progression of this syndrome. These are inflammatory/immunology, microbiology, and genetic. An impairment of neutrophil chemotaxis, phagocytosis, and bactericidal activities accompanied by a decrease in natural killer cell-mediated cell killing via myeloperoxidase deficiency and low integrin expression have been widely reported. In addition, there is functional impairment of the immune-mediated mechanism of monocytic and lymphocytic cells to pathogens, depression of helper/suppressor T-cells ratio, elevation of serum IgG, and degenerative changes of plasma cells were identified. Furthermore, disruption of fibroblast and cementoblast function with defective periodontal ligament attachment and gingival epithelium has been observed the above mentioned have been widely reported in the literature as host contributory factor in the development of PLS. [16],[17]

The presence of virulent Gram-negative capnophilic and facultative anaerobic pathogens mainly actinobacillus actnomycetemocomitans, streptococcus organisms and some viral organisms in the periodontal pockets and plaques has been thought to be an initiating factors. [5],[8] Studies have established the role of actinobacillus actnomycetemocomitans in the propagation and progression of the rapid destruction of the periodontium. This has been linked to the release of leukotoxins, endotoxin, epitheliotoxin, collagenase, and fibroblast inhibitory by the organism. [17] Other microbial agents including Gram-negative anaerobes such as porphyromonas gingivalis, fusobacterium nucleatum, treponema denticola and some viral agent such as Epstein-Barr virus have also been suggested not only to have causal effects on the periodontal breakdown but also in the cutaneous lesions of PLS. [1],[9]

Recently, the molecular basis underlying the etiopathogenesis of PLS has been established. A genetically demonstrated loss-of-function mutations affecting both alleles of the lysosomal protease CTSC gene in patients with PLS and subsequent dysregulation of localized polymorphonuclear leucocytes in inflamed periodontal tissues has been confirmed. [9],[13] The CTSC gene, which is located on chromosome 11q14.1-q14.3 has endopeptidase activity, a lysosomal protein and is expressed in epithelial regions commonly affected by PLS including palms, soles, knees, and keratinized oral gingival. [12],[13] Furthermore, high levels of expression of this gene have been found in various immune cells including polymorphonuclear leukocytes, macrophages, and their precursors. [9],[10] lysosomal protease enzyme plays an important role in maintaining the balance between oral microflora and immune system through protein degradation and proenzyme activation. Hence, a mutation in this gene with consequent dysfunction of this enzyme leads to the altered host response to pathogenic microorganisms in dental plaque and periodontal pocket. It is documented in the literature that alterations in CTSC gene lead to prepubertal periodontitis in PLS patients. [18],[19]

Haim-Munk syndrome has also been linked to mutation in CTSC gene with similar characteristic palmoplantar keratosis of the hands and feet however PLS differs from Haim-Munk syndrome in symptoms such as arachnodactyly, acroosteolysis, and onychogryphosis, which are only present in Haim-Munk syndrome. [9] These symptoms were not observed in our case hence Haim-Munk syndrome was ruled out. When there is the premature loss of the deciduous and/or permanent teeth, one should also consider Acrodynia, a condition is usually caused by mercury intoxication which is also known as Feer's syndrome. Here, one may observe a red desquamative process involving both the extremities. Furthermore, there is erythrocyanosis, muscle pain, insomnia, sweating, tachycardia, and psychic disturbances. Other differentials include hypophosphatasia condition where teeth are prematurely shed and are hypoplastic where increased amounts of phosphoethanolamine in the urine confirmed the diagnosis, nonsyndromic prepubertal periodontitis and localized juvenile periodontitis neither of which exhibit CTSC gene mutation. Other conditions to be considered in the differential diagnosis of PLS are palmoplantar hyperkeratosis of Unna Thost,  Mal de Meleda More Details, Howel-Evans syndrome, keratosis punctata, keratoderma hereditarium mutilans (Vohwinkel's syndrome) and Greither's syndrome. However, while these entities are associated with palmoplantar hyperkeratosis, there is no periodontopathy. [1],[9],[10] The management of PLS requires a multidisciplinary approach with the active participation of the dentist, dermatologist and pediatrician. Treatment of the oral component of the disorder must be done in concert with that of the dermatological aspect. Early recognition would help in reducing the devastating sequelae of this syndrome. Sadly, this was not the case in this report. Following the treatment protocol for periodontal therapy proposed by Ullbro et al. [7] through scaling and polishing aimed at eliminating the reservoir of causative organisms was done. This we hope would facilitate the healing of the oral tissues. Oral retinoids such as acitretin and isotretinoin have proven to be beneficial in treating both the oral and cutaneous lesions of PLS and is usually started during the eruption of permanent dentition and is followed till the normal developmental process is complete. [7],[9],[10] Unfortunately, this patient defaulted which is understandable in Africa setting where patient due to their health belief do not come back for follow-up once they notice an improvement in their status. The exact number of PLS cases cannot be given as some are not reported while others are mentioned twice or more. However, the global cases of PLS published in the scientific literature have been estimated to be about 700 cases, although cases from Africa regions are relatively few. [4],[21],[22]

In addition, the paucity of reported case in scientific literature from Africa could be attributed to cultural value and taboo associated with consanguineous relationship although this cannot be totally ruled out in our case evidenced by the death of four siblings with similar skin and oral presentations. Furthermore, observed in our case is the fact that the patient presented primarily because of oral lesions hence dentists might be the first to pick this condition which requires a high index of suspicion.

  References Top

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  [Figure 1], [Figure 2], [Figure 3]

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