Year : 2009 | Volume
: 21 | Issue : 1 | Page : 21--24
S Sujatha, Namita Raghav
Department of Oral Medicine, Diagnosis and Radiology, MS Ramaiah Dental College and Hospital, MSRIT Post, New BEL Road, Bangalore-560 054, Karnataka, India
Department of Oral Medicine, Diagnosis and Radiology, MS Ramaiah Dental College and Hospital, MSRIT Post, New BEL Road, Bangalore-560 054
Papillon-Lefevre syndrome (PLS) is a very rare syndrome of autosomal recessive inheritance characterized by palmar-plantar hyperkeratosis and early onset of a severe destructive periodontitis, leading to premature loss of both primary and permanent dentitions. The palmar-plantar keratoderma typically has its onset between the ages of 1 and 4 years and severe periodontitis starts at the age of 3 or 4 years. The exact pathogenesis of these clinical events remains mainly speculative. An early diagnosis of the syndrome can help preserve the teeth by early institution of treatment, using a multidisciplinary approach. This paper describes a case of PLS with classic clinical features and briefly reviews the relevant literature.
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Sujatha S, Raghav N. Papillon-Lefevre syndrome.J Indian Acad Oral Med Radiol 2009;21:21-24
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Sujatha S, Raghav N. Papillon-Lefevre syndrome. J Indian Acad Oral Med Radiol [serial online] 2009 [cited 2022 Oct 6 ];21:21-24
Available from: https://www.jiaomr.in/text.asp?2009/21/1/21/57774
Papillon-Lefevre syndrome (PLS) or keratosis palmoplantaris with periodontopathia or palmoplantar keratoderma with periodontosis was first described by Papillon and Lefevre in 1924.  The clinical manifestations include palmoplantar hyperkeratosis, with a precocious, rapidly progressive periodontal disease that results in premature exfoliation of primary and permanent dentitions.  Gorlin et al. have suggested that calcification of the dura mater is a third component of the syndrome. 
PLS is a genetically homogeneous autosomal recessive disorder with a locus mapped on chromosome 11q14-q21. , The prevalence of PLS is 1-4 per million individuals with no sex predilection and no racial predominance. ,, A genetic predisposition, with greater frequency of occurrence in consanguineous offspring, has been reported.  Variable findings in the syndrome include retardation of somatic development, follicular hyperkeratosis, nail dystrophy, and hyperhidrosis. 
A 17-year-old male patient presented with a complaint of exfoliation of teeth since 4-5 years. History revealed that his deciduous teeth had erupted normally but exfoliated gradually by the age of 4-6 years. Similarly, his permanent teeth too were exfoliated prematurely after erupting normally. There was a history of recurrent swelling of gums and foul breath followed by loosening and exfoliation of teeth. He was born to non-consanguineous parents after an uneventful pregnancy and birth. There was no family history of similar complaints. At the age of 3 years, his parents noticed a progressive thickening of palmoplantar skin associated with marked aggravation of erythema, scaling and dryness of skin during the eruption of teeth. The lesions became worse during winters, with fissuring and bleeding from fissures.
On cutaneous examination well-demarcated keratotic and confluent plaques affecting the skin of the palmar and plantar surfaces as well as the skin over the dorsal surfaces of finger joints were seen [Figure 1] and [Figure 2]. The skin was dry and rough on palpation. The hair and nails appeared normal. Intra-oral examination revealed multiple missing teeth (11, 12, 14, 15, 16, 17, 21, 22, 24, 25, 26, 27, 31, 32, 36, 37, 41, 42, 43, 45, 46 and 47) and the overlying mucosa was normal on the edentulous ridges. The gingiva in relation to the permanent teeth was erythematous, soft and edematous with deep periodontal pockets and bleeding on probing. Despite the severity of the periodontal involvement, no local factors were present [Figure 3].
Panoramic radiograph of the patient showed severe alveolar bone loss in relation to the existing permanent teeth up to the level of apical third of roots giving the teeth a "floating in air" appearance [Figure 4]. There was no evidence of intracranial calcification on lateral cephalogram. Other systemic examination, routine laboratory investigations and chest x-ray were normal. Punch biopsy of the skin and palms revealed extensive hyperkeratosis, focal hypergranulosis and acanthosis, and mildly dilated vascular structures in upper dermis [Figure 5].
The skin lesions were treated using emollients, acitretin and salicylic acid. The gingival inflammation improved to some extent with periodontal cleaning and antibiotic therapy. Full mouth extraction followed by the fabrication of complete denture prosthesis was done.
PLS is an uncommon autosomal recessive type-IV palmoplantar ectodermal dysplasia.  It usually manifests itself between the ages of 6 months to 4 years, coinciding with the eruption of primary teeth.  The two cardinal diagnostic features of the syndrome are palmoplantar keratosis and an early-onset form of aggressive periodontitis.
The palmoplantar keratoderma typically has its onset between the ages 1 and 4 years. The sharply demarcated erythematous keratotic plaques may occur focally, but usually involve the entire surface of the palms and soles, sometimes extending onto the dorsal surfaces of the hands and feet. Often, there is associated hyperhidrosis of the palms and soles resulting in a foul-smelling odor. In addition, psoriasiform plaques may be seen on the elbows and knees. The findings may worsen in winter and be associated with painful fissures. Other sites that may be affected include the eyelids, labial commisures, legs, thigh and axillae. The hair is usually normal, but the nails in advanced cases may show transverse grooving and fissuring. ,
The second major feature of PLS is severe periodontitis, which starts at the age of 3 or 4 years. The eruption of primary teeth occurs at the expected ages in the normal sequence, with the teeth being of normal form and structure. Eruption of the primary dentition into the oral cavity is accompanied by severe gingival inflammation and a generalized aggressive periodontitis, resulting in tooth mobility. The resulting periodontitis characteristically is unresponsive to traditional periodontal treatment modalities and the primary dentition is usually exfoliated prematurely by age 4 or 5 years. After exfoliation of the primary dentition, the gingival inflammation resolves. As the permanent teeth erupt, the same sequence of events recurs and, without intervention, most of the permanent teeth are lost by 15-17 years of age, although the third molars are sometimes spared. Severe resorption of alveolar bone gives the teeth a 'floating-in-air' appearance on dental radiographs. ,
Cathepsin C, a lysosomal protease enzyme plays an important role in maintaining the balance between the oral microflora and the immune system through protein degradation and pro-enzyme activation. Lack of cathepsin activity in PLS may be associated with a reduced host response against virulent pathogens in dental plaque and possibly at other sites. In addition to genetic alterations, several environmental and host factors are involved in the PLS periodontitis including (1) specific virulent bacterial and viral infection of periodontium, particularly Actinobacillus actinomycetemcomitans, Prevotella nigrescens, Fusobacterium nucleatum, Porphyromonas gingivalis, Eikenella corrodens, Peptostreptococcus, Cytomegalovirus, and Epstein-Barr type 1 virus; (2) impaired neutrophil chemotaxis, migration, and phagocytotoxic functions, and increased superoxide production; (3) reduced functional activity of monocytes elicited by decreased phagocytosis, increased tendency to aggregate, and impaired Fc-receptor function; (4) decreased mitogenic activity of lymphocytes, and reversed ratio of T-helper to T-killer cells; (5) degenerative changes of plasma cells and elevation of serum immunoglobulin (IgG); and (6) disruption of fibroblast and cementoblast function combined with defective periodontal ligament attachment and gingival epithelium, and imbalance of collagenolytic activity in the periodontal ligament. 
In addition to the skin and oral findings, patients may have decreased neutrophil, lymphocyte, or monocyte functions and an increased susceptibility to bacteria, associated with recurrent pyogenic infections of the skin in approximately 25% of Papillon-Lefevre patients.  Pyogenic liver abscess is increasingly recognized as a complication of PLS associated with impairment of the immune system. 
Another component of PLS may be radiographic evidence of intracranial calcification in choroid plexus and tentorium. Although this has been taken as a cardinal feature, being inconsistent it is not considered important for the diagnosis. Histopathological examination reveals non-specific hyperkeratosis, acanthosis, focal parakeratosis, psoriasiform hyperplasia, torturous capillaries in dermal papillae and superficial lymphocytic infiltration. ,
The differential diagnoses include Hiam-Munk syndrome and hypophosphatasia. Hiam-Munk syndrome also exhibits arachnodactyly, acro-osteolysis, atrophy of nails, and deformity of the phalanges in the hands. In hypophosphatasia, deficiency of alkaline phosphatase activity is seen, but in our case the values were within normal limits and therefore this differential diagnosis could be excluded. ,
A multidisciplinary approach is important for the care of patients with PLS. The skin manifestations of PLS are usually treated with emollients. Salicylic acid and urea may be added to enhance their effects. Oral retinoids including acitretin, etretinate, and isotretinoin are the mainstay of the treatment of both the keratoderma and periodontitis associated with PLS. Treatment may be more beneficial if it is started during the eruption and maintained during the development of the permanent teeth. The periodontitis in PLS is usually difficult to control. Identification of specific periodontal pathogens and antibiotic therapy appropriate to these microorganisms, along with extraction of severely periodontally compromised teeth, can prolong the viability of non-affected teeth. In the future, stem cell therapy can be expected to open up new vistas in the dental treatment of such children. 
PLS threatens children and their parents with the prospect of edentulism if left untreated. Hence, early diagnosis and intervention is essential to provide appropriate and comprehensive dental care. For edentulous patients, oral rehabilitation is required; this includes partial or complete denture prosthetic replacement. Osseointegrated implants are an option for the future and can have a great impact psychosocially by restoring esthetics as well as function. ,
PLS can adversely affect growing children psychologically, socially and esthetically; therefore, awareness of this syndrome is essential. Early dental evaluation and parental counseling as a part of preventive dental treatment is essential for providing complete psychosocial rehabilitation for PLS children; a multidisciplinary approach may improve the prognosis and quality of life of these children.
The authors are grateful to Dr. H.N. Shamao Rao, Principal and Professor, MS Ramaiah Dental College and Hospital, Bangalore for his support and guidance.
|1||Papillon MM, Lefevre P. Two cases of symmetrical, familial palmar and plantar keratosis of brother and sister: Coexistence in two cases with serious dental changes. Bull Soc Fr Dermatol Syphiligr 1924;31:82-7.|
|2||Haneke E. The Papillon-Lefevre syndrome: Keratosis palmoplantaris with periodontopathy: Report of a case and review of the cases in the literature. Hum Genet 1979;51:1-35.|
|3||Gorlin RJ, Sedano H, Anderson VE. The syndrome of palmar-plantar hyperkeratosis and premature periodontal destruction of the teeth: A clinical and genetic analysis of the Papillon-Lefevre syndrome.J Pediatr 1964;65:895-908.|
|4||Laass MW, Hennis HC, Preis S, Stevens HP, Jung M, Leigh IM, et al. Localization of a gene for Papillon-Lefevre syndrome to chromosome 11q14-q21 by homozygosity mapping. Hum Genet 1997;101:376-82.|
|5||Hart TC, Bowden DW, Ghaffar KA, Wang W, Cutler CW, Cebeci I, et al. Sublocalization of the Papillon-Lefevre syndrome locus on 11q14-q21. Am J Med Genet 1998;79:134-9.|
|6||Pareek SS, Al-Aska AK. Papillon-Lefevre syndrome: A report of six cases in one family. Int J Dermatol 1998;37:268-70.|
|7||Giorgi VD, Martini L, Prignano F, Donati E, Moretti S. Papillon-Lefevre syndrome in two sisters. J Eur Acad Dermatol Venereol 1996;6:57-61.|
|8||Hattab FN, Amin WM. Papillon-Lefevre syndrome with albinism: A review of the literature and report of 2 brothers. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100:709-16.|
|9||Janjua SA, Khachemoune M. Papillon-Lefevre syndrome: Case report and review of the literature. Dermatol Online J 2004;10:13.|
|10||Hattab FN, Rawashdeh MA, Yassin OM, al-Momani AS, al-Ubosi MM. Papillon-Lefevre Syndrome: A review of the literature and report of 4 cases. J Periodontol 1995;66:413-20.|
|11||Shah J, Goel S. Papillon-Lefevre Syndrome: Two case reports. Indian J Dent Res 2007;18:210-3.|
|12||Ghaffar KA, Zahran FM, Fahmy HM, Brown RS. Papillon-Lefθvre syndrome: Neutrophil function in 15 cases from 4 families in Egypt. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:320-5.|
|13||Almuneef M, Al Khenaizan S, Al Ajaji S, Al-Anazi A. Pyogenic liver abscess and Papillon-Lefevre syndrome: Not a rare association. Pediatrics 2003;111:e85-8.|
|14||Mahajan VK, Thakur NS, Sharma NL. Papillon-Lefevre Syndrome. Indian Pediatr 2003;40:1197-200.|