Case of the Month - Sibar Institute of Dental Sciences, Papillon-Lefevre syndrome, Palmo-plantar hyperkeratosis, Prepubertal periodontitis, SIDS - Sibar Institute of Dental Sciences, Sibar Dental College, Top Dental Colleges in Andhra Pradesh, Best Dental College in India, Best Dental colleges in AP, Best Dental Colleges in India, Dental Colleges offering Postgraduate studies in India, Dental Colleges offering Postgraduate studies in AP, Dental colleges under Dr NTR UHS, Top Dental Colleges under DR NTR UHS, Dental Colleges in South India, Dental colleges having International collaborations, Dental colleges with Student Exchange Programmes, Dental colleges with Foreign colloborations

Case of the Month - April 2009

Papillon –Lefevre syndrome - A Case Report

Abstract:
Papillon -Lefevre syndrome is a rare disease associated with prepubertal periodontitis, premature loss of both deciduous and permanent teeth and palmo-plantar keratosis. 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. An early diagnosis and intervention can help to preserve teeth and prevent their premature exfoliation. We present a case of Papillon-Lefevre syndrome with all characteristic features.

Introduction:
Papillon -lefevre syndrome was first described in 1924 by two French physicians Papillon and Lefevre. This autosomal recessive disorder predominantly demonstrates dermal and oral manifestations. This syndrome is characterized by palmar-plantar hyperkeratosis and severe destruction of the periodontal tissues in the deciduous and permanent dentition.

Genetic studies of patients with Papillon- Lefevre syndrome mapped the major gene locus to an interval on chromosome 11q 14 and revealed mutation of the Cathepsin C gene. Parental consanguinity has been found in about 40%.

The prevalence of the syndrome is between 1 and 4 per million infants. The disorder has high frequency in Saudi Arabia3. The palmar plantar keratoderma typically has its onset between the ages of 1 and 4 yrs. Diffuse transgradient palmar- plantar keratosis develops and keratosis of the elbows and knees. Other less common sites include the legs, thighs, dorsal surface of the fingers and toes and rarely the trunk. The lesions are punctate and diffuse, with dry scaly skin and vary in thickness from one to several mm. In addition, some patients manifest a generalized hyperhidrosis, very fine body hair and a peculiar dirty -coloured skin. The symptoms may worsen in winter . Histopathological examination reveals nonspecific hyperkeratosis, acanthosis, focal parakeratosis, psoriasiform hyperplasia, tortuous capillaries in dermal papillae and superficial lymphocytic infiltration.

The oral manifestations consist of advanced periodontitis effecting both the dentitions soon after the eruption of the teeth. Inflammatory gingival enlargement, gingival ulceration and formation of deep pockets are frequently present. Even during the most active phase of periodontal destruction, the rest of the oral mucosal membrane is reported to be completely normal. Primary dentition is usually exfoliated prematurely by the age of 4 yrs and permanent dentition by the age of 13-16 years. Severe resorption of alveolar bone gives the teeth a "floating -in-air" appearance on dental radiographs.

In addition to the dermatologic and oral findings, patients may have decreased neutrophils, lymphocyte or monocyte functions and an increased susceptibility to bacterial infections leading to recurrent pyogenic infections of the skin5. Ectopic calcifications of the falx cerebri and choroid plexus have been reported. Pyoderma, furunculosis, pneumonia, hepatic abscesses and other infections have been documented. This syndrome should be distinguished from other conditions causing gingival inflammation and early loss of decidous and /or permanent teeth, such as leukocyte imbalances, mercury and radiation toxicities, acatalasia, hypophosphatasia, Hand-Schiller-Christian disease, Letterer-Siwe disease when the lab findings are all essentially within the normal limits.

A multidisciplinary approach is necessary in the management of patients with Papillon Lefevre syndrome. Emollients like salicylic acid are used for the treatment of skin manifestations. Oral retinoids like Acitretin, Etretinate and Isotretinoin, are the main stay of the treatment for both keratoderma and periodontitis. The periodontal disease may be arrested by improving oral hygiene, extraction of severely diseased teeth, scaling, systemic antibiotics and long term antimicrobial irrigation. In severely dentally compromised patients, implants could considerably enhance future therapeutic option.

Case report:
A 13-year-old female patient reported to the Department of Oral Pathology, Sibar Institute of Dental Sciences, Takkellapadu with a chief complaint of pain and swelling in the upper front teeth region since 3 months .Family history revealed a consanguineous marriage of her parents with, her sister and brother both suffering from a similar problem.

On examination, there were symmetrical, well demarcated, keratotic and confluent plaques affecting the skin of the palms ( fig-1) and soles ( fig-2) which extended to the dorsal surface of the feet ( fig-3) and hands ( fig-4). Similar presentation was also seen on both the elbows ( fig-5) .The skin was dry and rough on palpation.

On intraoral examination, mobility was present in all the teeth. The gingiva was red, soft and edematous with deep periodontal pockets and bleeding on probing ( fig-6 ). The mucosa in other areas of the oral cavity appears to be normal. OPG of the patient showed severe alveolar bone loss in relation to all the teeth which were present upto the level of apical third of the tooth giving the teeth a "floating - in - air" appearance (fig-7). Histopathology of the affected gingiva revealed stratified squamous epithelium with branching rete ridges (fig-8) and the underlying connective tissue was infiltrated with chronic inflammatory cells (fig- 9). The skin lesions were treated by emollients and salicylic acid. Extraction of teeth that had severe mobility with subsequent prosthesis construction was advised.

Discussion:
Papillon-Lefevre syndrome is an autosomal recessive disorder which predominantly demonstrates dermal and oral manifestations. It is characterized by palmar-plantar hyperkeratosis and severe destruction of the periodontal tissues in the deciduous and permanent dentition9. The onset of symptoms is between 1 and 4 yrs of age. In our case the skin and periodontal findings are consistent with the classical description of the syndrome .The skin lesions in this patient appeared in the 1st and 2nd decade of life. The dental history of the patient was also in accordance with the known symptoms of the syndrome ie, advanced periodontitis in both decidous and permanent dentition and develops soon after the eruption of the teeth and also extensive hyperplastic and hemorrhagic gingivitis.

Clinically, the patient had the characteristic skin lesions : symmetrical, well demarcated , keratotic and confluent plaques affecting the skin of the palms and soles which extended to the dorsal surface of the feet . Similar presentation was also seen on both the elbows .The skin was dry and rough on palpation. Intraoral findings were remarkable in our case with the characteristic features of advanced periodontitis with extensive hyperplastic and hemorrhagic gingivitis. The teeth that were present exhibited marked mobility. The radiograph of the patient showed: severe alveolar bone loss in relation to all the teeth which were present upto the level of apical third of the tooth giving the teeth a floating in air appearance. Histopathology of the affected gingiva revealed stratified squamous epithelium with branching rete ridges and the underlying connective tissue is infiltrated with chronic inflammatory cells. All these dental findings and the skin lesions are consistent with the characteristic features of Papillon -Lefevre syndrome. Multiple etiological factors have been proposed. Genetic studies of these patients mapped the major gene locus to an interval on chromosome 11q14 and revealed mutation of the Cathepsin - C - gene. This gene is important in the structural growth and development of the skin and is critical for appropriate immune response of myeloid and lymphoid cells. Loss of appropriate function of the Cathepsin - C gene is thought to result in an altered immune response to infection. In addition the altered gene may affect the integrity of the junctional epithelium surrounding the tooth. The exact cause of periodontal disease in Papillon- Lefevre syndrome has not been found but it has been attributed to leukocyte dysfunction and bacterial infection with Actinomyces actinomycetem comitans. Gingival infection , abscess formation, alveolar bone loss and destruction of periodontal ligament are probably the causative factors responsible for the premature exfoliation of the teeth.

The dermatological manifestations of Papillon-Lefevre syndrome are treated with emollients and salicylic acid4. Oral retinoids are the main stay of the treatment of both the kertoderma and periodontitis with this syndrome. Rigorous oral hygiene, chlorhexidine mouth rinses, frequent professional prophylaxis and periodic appropriate antibiotic therapy can delay the premature exfoliation of the teeth. The most effective antibiotic regimen is Amoxicillin and Clavulinate potassium1. Early extraction of teeth has also been advocated to prevent bone loss and allow preservation of solid base for subsequent use in artificial dentures.

Conclusion
We report a case of Papillon-Lefevre syndrome having all of the characteristic features. An alert diagnosis on part of the dentist, with an early intervention with retinoids can help to preserve teeth and prevent their premature exfoliation. Even if the patient comes at a later stage, appropriate periodontal treatment to prevent alveolar bone loss will facilitate future treatment with implant placement and subsequent prosthetic rehabilitation.

References:
1. Neville, Damm, Allen, Bouquot. Oral and maxillofacial pathology, 2nd edition, Elsevier publications, India , 2004, 156-158.
2. N.Thakker. Genetic analysis of Papillon -Lefevre syndrome. Oral diseases 2000,6 : 263.
3. Robert.J.Gorlin, M.Micheal Cohen Jr, Raoul C.M.Hennekam. Syndrome of the head and neck : 4th edition, Oxford university press, New York, 2001, 1101-1103.
4. Jigna Shah, Shweta Goel. Papillon-Lefevre syndrome - two case reports. Indian J Dent Res 2007, 18 : 210-3.
5. Janjua SA, Khachemoul .A, Papillon Lefevre syndrome : case report and review of the literature. Dermatol online J 2004, 10 : 13.
6. Dergman .R, Friedman - Birnbaun R : Papillon -Lefevre syndrome. A Study of the long term clinical course, recurrent Pyogenic infections and the effects of atretinate treatment. Br J Dermatol 1988,119,731-736.
7. Rudiger S, Peter Silka G, Flemmig TF. Combined systemic and local antimicrobial therapy of periodontal disease in Papillon- Lefevre syndrome- a report of two cases. J Clin periodontal 1999, 26 : 847-54.
8. Kressin .S, Herforth A, Preis S et al. Papillon-Lefevre syndrome- successful treatment with a combination of retinoid and concurrent systematic periodontal therapy: case report. Quintessence Int 1995, 26: 795-803..
9. Shafer, Hine , Lavy. Shafer's Text book of oral pathology, 5th edition ,Elsevier publication, India, 2006 , 560-561 10. H.Nitta, H.Kato, M.Umeda, S.Kuwata, I.Ishikawa. Papillon-Lefevre syndrome : analysis of HLA-antigens. Oral diseases 2000,6,278-281 .

Appendix

Fig 1 - HYPERKERATINIZATION OF THE PALMS	Fig 2 - HYPERKERATINIZATION OF THE SOLES	Fig 3 - HYPERKERATINIZATION ON THE THE DORSAL SURFACE OF THE LEGS

Fig 4 - HYPERKERATINIZATION ON DORSAL OF THE HANDS	Fig 5 - HYPERKERATINIZATION ON THE ELBOWS	Fig 6 - ADVANCED PERIODONTITIS WITH GINGIVAL SWELLING

Fig 7 - OPG REVEALS “FLOATING - IN – AIR” APPEARANCE	Fig 8 - 10x VIEW SHOWS BRANCHING RETERIDGES AND CHRONIC INFLAMMATORY CELL INFILTRATE	Fig 9 - 40X VIEW SHOWING CHRONIC INFLAMMATORY CELL INFILTRATION