Year : 2008 | Volume
: 26 | Issue : 4 | Page : 171--174
Papillon-Lefevre syndrome: A case report
P Subramaniam, S Mathew, KK Gupta
Department of Pedodontics and Preventive Dentistry, The Oxford Dental College, Hospital and Research Centre, Bommanahalli, Hosur Road, Bangalore - 560 068, Karnataka, India
Department of Pedodontics and Preventive Dentistry, The Oxford Dental College, Hospital and Research Centre, Bommanahalli, Hosur Road, Bangalore - 560 068, Karnataka
Papillon-Lefevre syndrome is a rare autosomal recessive genetic disorder. The clinical manifestations include palmer planter hyperkeratosis with precocious progressive periodontal disease that results in premature exfoliation of primary and permanent dentitions. Patients are often edentulous at an early age. This is a case report of prosthodontic rehabilitation of a 15-year-old girl with Papillon-Lefevre syndrome.
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Subramaniam P, Mathew S, Gupta K K. Papillon-Lefevre syndrome: A case report.J Indian Soc Pedod Prev Dent 2008;26:171-174
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Subramaniam P, Mathew S, Gupta K K. Papillon-Lefevre syndrome: A case report. J Indian Soc Pedod Prev Dent [serial online] 2008 [cited 2021 Jun 20 ];26:171-174
Available from: https://www.jisppd.com/text.asp?2008/26/4/171/44037
The Papillon-Lefevre syndrome (PLS) is a rare genodermatosis of autosomal recessive inheritance manifesting as palmer plantar hyperkeratosis with periodontitis.  It was first described by two French physicians, Papillon and Lefevre, in 1924. It has a prevalence of 1-4 cases per million persons and both males and females are equally affected with no racial predominance. , The disorder is characterized by diffuse palmoplantar keratoderma and premature loss of both deciduous and permanent teeth. The palmoplantar keratoderma typically has its onset between the ages one and four years.  The sharply demarcated erythematous keratotic plaques may occur focally, but usually involve the entire surface of palms and soles resulting in foul-smelling odor.  Well-demarcated psoriasiform plaques occur on elbows and knees.  This may worsen in winter and be associated with painful fissures.
The second major feature of PLS is severe periodontitis, which starts at the age of three or four years.  The development and eruption of deciduous teeth proceeds normally, but their eruption is associated with gingival inflammation and subsequent rapid destruction of the periodontium. The resulting periodontitis characteristically is unresponsive to traditional periodontal treatment modalities and the primary dentition is usually exfoliated prematurely by the age four years. After exfoliation, the inflammation subsides and gingiva appears healthy. However, with eruption of the permanent dentition the process of gingivitis and periodontitis is usually repeated and there is subsequent premature exfoliation of the permanent teeth, although the third molars are sometimes spared. ,
The degree of dermatologic involvement may not be related to the level of periodontal infection.  Nail changes such as transverse grooving and fissuring are apparent in advanced cases. In addition to skin and oral findings, patients may have decreased neutrophils, lymphocytes, or monocytic function and increased susceptibility to bacterial infection resulting in recurrent pyogenic infection of skin. 
Radiographic features are characterized by generalized loss of alveolar bone. Gorlin et al. have added the third feature of dural calcification.  Reyes also observed radiographic evidence of intracranial calcification.  Histopathologic findings of affected skin consists of hyperkeratosis, occasional patches of parakeratosis, acanthosis, and slight perivascular inflammatory infiltrate. 
Although the cause of PLS is not well understood, it has been reported that loss of the functional mutation effecting both the alleles of cathepsin C gene, located on chromosome 11q14.1-q14.3 is associated with PLS. , The cathepsin C gene encodes a cystine lysosomal protease, also known as dipeptidyl peptidase I , which functions to remove dipeptides from the amino terminus of protein substrate. It also has endopeptidase activity. Cathepsin C gene is expressed in the epithelial region commonly affected by PLS such as palms, soles, knees, and keratinized oral gingiva. It is also expressed at high levels in various immune cells including polymorphonuclear leukocytes, macrophages, and their precursors. Several mutations have been reported in the cathepsin C gene in individuals from diverse ethnic groups.
An increased prevalence of parental consanguinity has been reported in PLS patients.  All PLS patients are homozygous for the same cathepsin C gene mutation inherited from a common ancestor. It would be pertinent to mention that there are reports of at least six cases of late onset variation of PLS without underlying cathepsin C gene mutation. 
The cause of the periodontal disease and increased susceptibility to infection is attributed to decreased neutrophil phagocytosis, bacterial infection, and impaired reactivity to T- and B-cell mitogens. ,,,
A 15-year-old female patient presented to the department of Pedodontics and Preventive Dentistry, The Oxford Dental College, Hospital and Research Centre, Bangalore, India, with the chief complaint of multiple loss of teeth.
Clinical history revealed that she had normal emergence of deciduous teeth at 8-9 months of age, which started loosening at three years and were all eventually lost by four years of age. Patient was not sure about the time of eruption of permanent teeth, but described gingival bleeding during brushing and eating, after the eruption of permanent teeth. There was loosening of permanent teeth from l0 years of age and eventually all the permanent teeth were lost by 12 years of age, except for one mobile lower anterior tooth. Bleeding was also associated at the time of tooth loss. The sequence of tooth loss was incisors followed by molars, canines, and premolars. Hence, the patient expressed a keen desire for replacement of all her lost teeth.
Medical history was noncontributory. Parents were not of consanguineous marriage. Mother had a full term normal uneventful pregnancy. Natal history revealed that the patient presented with eruptions on the scalp, legs, feet, arms, and hands at birth, for which the parents did not seek any treatment. Subsequently, there was reddening of the palms and soles at six months of age, which gradually thickened and became rough and scaly.
The patient was moderately built with a steady gait. Her physical and mental development was also normal. Except for a slight articulatory defect, her speech was normal and she had the ability to comprehend and communicate satisfactorily.
Dermatological examination revealed dry skin with normal development of hair and nails. There were symmetric, well-demarcated, yellowish, keratotic, and confluent plaques affecting the skin of her palms and soles, also extending onto the dorsal surfaces of hands and feet. There was presence of pyogenic infection in the legs [Figure 1] and [Figure 2].
Intraoral examination showed premature loss of all teeth, except for the left mandibular canine which was covered with deposits and it showed severe mobility. No other abnormality was detected in relation to soft tissues. Patient had a reduced facial height due to resorption of the alveolar ridge [Figure 3].
Panaromic view showed generalized loss of alveolar bone, complete loss of bone support around the mandibular left canine, and presence of all third molars. Intracranial calcifications were evident on the lateral skull radiograph [Figure 4] and [Figure 5].
Routine blood investigations and liver function tests were carried out and were found to be within the normative range of values.
Since the patient was a young teenage girl, it was necessary to manage the esthetic needs of the patient as a priority. It was appropriate to give her complete dentures, considering her functional requirements, such as mastication and speech.
Prior to the routine clinical procedure for complete dentures, the mandibular left canine was extracted. The dentures were fabricated in the laboratory and inserted into the patient's mouth. Routine postdenture instructions were given to the patient [Figure 6].
Rehabilitation with complete dentures transformed this teenage girl from an edentulous state to a fully dentate condition. It gave her immense confidence and every reason to smile [Figure 7] and [Figure 8]. The patient was continuously monitored for one year and was found to be comfortable with the dentures. She continues to be on a regular follow up. The patient was referred to a dermatologist and was prescribed both oral and topical retinoid preparations.
Some of the other conditions where patients present with severe periodontitis and dermatological lesions are prepubertal periodontitis, and Haim-Munk syndrome (HMS).
Further, these conditions have been described as allelic variants of cathepsin C gene. , Hence, we need to consider only HMS and prepubertal periodontitis in the differential diagnosis of PLS.
HMS has been described as an autosomal recessive genodermatosis characterized by congenital palmoplantar keratoderma and progressive early onset periodontitis.  In addition to palmoplantar keratosis and periodontitis, other clinical findings in this condition include recurrent pyogenic skin infections, acro-osteolysis, atrophic changes of the nails, arachnodactyly, and a peculiar radiographic deformity of the finger consisting of tapered, pointed phalangeal ends, claw-like volar curve, and pes planus. In contrast to PLS, the cutaneous findings in HMS have been reported to be more severe and extensive.  The periodontium in HMS may be less-severely affected than in PLS, but gingival inflammation and alveolar-bone destruction are present and severe.  Although the palmoplantar findings and periodontitis are suggestive of HMS, the absence of other distinct clinical features, like nail deformities and arachnodactyly prevented us from diagnosing it as HMS.
Prepubertal periodontitis is another rare genodermatosis with an etiology attributed to a cathepsin-C gene mutation.  It is characterized by rapidly progressive early onset periodontitis with destruction of the periodontium of deciduous and permanent teeth. Prepubertal peridontitis may be localized or generalized. It may occur as a part of recognized syndrome or as an isolated nonsyndromic disorder. Both autosomal dominant and autosomal recessive patterns of familial transmission have been described for prepubertal periodontitis. The radiographic presentation of alveolar bone loss in prepubertal periodontitis in many cases appears similar to that observed in PLS. But presence of palmoplantar keratoderma is not indicative of prepubertal periodontitis.
Also pyogenic infection, a common feature of PLS was seen in both the legs of the present case. But there was no infection of the liver, which is considered as one of the complications.
The presence of skin lesions, along with complete loss of teeth due to severe periodontitis, and intracranial calcifications enabled us to diagnose the present condition as PLS.
A multidisciplinary approach is important for the care of patients with PLS. The skin manifestations are usually treated with emollients and oral retinoids. Oral retinoids including acitretin, etretinate, and isotretinoin are the mainstay of treatment of both the keratoderma and periodontitis associated with PLS.  Treatment may be more beneficial if it is started during eruption and maintained during the development of permanent teeth. But the periodontitis in PLS is usually difficult to control.
The PLS debilitates individuals socially, psychologically, and physically. Thus, prosthetic replacement in such patients is an age specific, speciality treatment involving initial replacement with complete or partial dentures and future consideration for an implant-supported prosthesis.  In the present case, prosthetic rehabilitation was considered as it would provide immediate satisfaction to the patient in terms of esthetics and function. The placement of implants was doubtful considering the poor overall bone support. Also, due to socioeconomic reasons complete dentures were preferred.
|1||Jain V, Gupta R, Prakash H. Prosthodontic rehabilitation in Papillon-Lefevre syndrome: A case report. J Indian Soc Pedod Prev Dent 2005;23:96-8.|
|2||Gorlin RJ, Sedano H, Anderson VE. The syndrome of palmar-plantar hyperkeratosis and premature periodontal destruction of the teeth. J Pediatr 1964;65:895-908.|
|3||Cury VF, Costa JE, Gomez RS, Boson WL, Loures CG, De ML. A novel mutation of cathepsin C gene in Papillon Lefevre syndrome. J Periodontol 2002;73:307-12. |
|4||Bach JN, Levan NE. Papillon-Lefevre syndrome. Arch Dermatol 1968;97:154-8.|
|5||Siragusa M, Romano C, Batticane N, Batolo D, Schepis C. A new family with Papillon-Lefevre syndrome: Effectiveness of etretinate treatment. Cutis 2000;65:151-5.|
|6||Hart TC, Hart PS, Michalec MD, Zhang Y, Firatli E, Van Dyke TE, et al. Haim-Munk syndrome and Papillon-Lefθvre syndrome are allelic mutations in cathepsin C. Periodontol 2000;37:88-94.|
|7||Hanekes 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.|
|8||Ullbro C, Crosner CG, Nederfors T, Thelstrup-Pederson K. Dermatologic and oral finding in a cohort of 47 patients with Papillon Lefevre syndrome. J Am Acad Dermatol 2003;48:345-51.|
|9||Almuneef M, AI Khenaizan S, AI-Anazi A. Pyogenic liver abscess and Papillon-Lefevre syndrome: Not a rare association. Pediatrics 2003;111:85-8.|
|10||Newman MG, Takei HH, Carranza FA. Clinical periodontology. 9th ed. Pennysylvania: Saunders; 2003.|
|11||Reys VO, King-Ismael D, Abad-Venida L. Papillon Lefevre syndrome. Int J Dermatol 1998;37:268-70.|
|12||Angel TA, Hsu S, Kornbleuth SI, Kornbleuth J, Kramer EM. Papillon Lefevre syndrome: A case report of four affected siblings. J Am Acad Dermatol 2002;46:S8-10. |
|13||Toomes C, James J, Wood AJ, Wu CL, McCrmick D, Lench N, et al. Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Nat Genet 1999;23:421-4.|
|14||Hart TC, Hart PS, Bowden DW, Michalec MD, Callison SA, Walker SJ, et al. Mutation of cathepsin C gene are responsible for Papillon-Lefevre Syndrome. J Med Genet 1999;36:881-7.|
|15||Itni PH. Classification of autosomal dominant palmoplanter keratoderma: Past and future. Dermatology 1992;185:163-5.|
|16||Stevens HP, Kelsell DP, Bryant SP, Bishop DT, Spurr NK, Weissenbach J, et al. Linkage of an American pedigree with palmoplanter keratoderma and malignancy (Palmoplanter ectodermal dysplasia type III) to 17q24: Literature survey and proposed updated classification of the keratodermas. Arch Dermatol 1996;132:640-51.|
|17||Haim S, Munk J. Keratosis palmo-plantaris congenital, with perikontosis, arachnodactyly and peculiar deformity of the terminal phalanges. Br J Dermatol 1965;77:42-54.|
|18||Pilger U, Hennies HC, Truschnegg A, Aberer E. Late-onset Papillon Lefevre syndrome without alteration of cathepsin C gene. J Am Acad Dermatol 2003;49:240-3.|
|19||Hart TC, Hart PS, Michalec MD, Zhang Y, Firatli E, Van Dyke TE, et al. Haim Munk syndrome and Papillon Lefevre syndrome are allelic mutation in cathepsin C. J Med Genet 2001;38:79.|