|Year : 2012 | Volume
| Issue : 2 | Page : 122-127
Rehabilitation of three siblings with Papillon-Lefevre syndrome
Gouri V Anehosur1, Harikishore Bhat2, Ramesh K Nadiger3, Venkatesh S Anehosur4
1 Department of Prosthodontics and Geriatric Dentistry, SDM College of Dental Sciences & Hospital, Sattur, Dharwad, India
2 Department of Oral and Maxillofacial Surgery, Sri Sai College of Dental Surgery, Opp. Shiv Sagar, Kothrepally, Vikarabad, India
3 Department of Prosthodontics, SDM College of Dental Sciences & Hospital, Sattur, Dharwad, India
4 Department of Oral and Maxillofacial Surgery, SDM College of Dental Sciences & Hospital, Sattur, Dharwad, India
|Date of Web Publication||4-Sep-2012|
Gouri V Anehosur
Department of Prosthodontics and Geriatric Dentistry, SDM College of Dental Sciences & Hospital, Sattur, Dharwad
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Papillion-Lefevre Syndrome is a rare autosomal recessive disorder characterized by severe early onset periodontopathia and palmoplantar hyperkeratosis leading to premature loss of primary and permanent dentition. PLS is caused by mutations in cathepsin C (CTSC) gene. It is transmitted with an estimated frequency of one to four per million individuals. In this case report, we present clinical and other relevant investigations of three siblings with symptoms typical of Papillion-Lefevre Syndrome. The three siblings were born of a second-degree consanguineous marriage, where the parents were first cousins. All the siblings reported with mobility, eventually leading to loss of teeth and masticatory inefficiency. All showed hyperkeratosis of palms and soles, with youngest sibling showing mild to severe form of severe generalized periodontal destruction. The elder two siblings were given dentures. The youngest sibling is undergoing periodontal therapy and has received partial dentures for missing teeth.
Clinical Relevance to Interdisciplinary Dentistry
- PLS is a rare autosomal disorder which needs to be diagnosed early.
- Timely intervention of periodontal therapy helps in decreasing the loss of teeth at an early stage.
- This facilitates growth of jaws and eventual successful placement of implants.
- Dermatological treatment and psychological counseling are also mandatory
- Helps to educate the parents and family members. Needs team approach for successful outcome.
Keywords: Consanguineous marriage, juvenile periodontitis, palmoplantar keratosis, Papillon-Lefevre syndrome, prosthodontic rehabilitation, pyogenic liver abscess
|How to cite this article:|
Anehosur GV, Bhat H, Nadiger RK, Anehosur VS. Rehabilitation of three siblings with Papillon-Lefevre syndrome. J Interdiscip Dentistry 2012;2:122-7
|How to cite this URL:|
Anehosur GV, Bhat H, Nadiger RK, Anehosur VS. Rehabilitation of three siblings with Papillon-Lefevre syndrome. J Interdiscip Dentistry [serial online] 2012 [cited 2019 Jun 16];2:122-7. Available from: http://www.jidonline.com/text.asp?2012/2/2/122/100606
| Introduction|| |
Papillon-Lefevre Syndrome (PLS), was first described by two French physicians Papillon and Lefevre in 1924. It was regarded as an extremely rare genodermatosis inherited as an autosomal recessive trait affecting children between the age group of 1 and 4 years, manifesting as palmo plantar keratosis, with a precocious, rapidly progressive periodontitis that results in premature exfoliation of primary and permanent dentition.  The prevalence being 1-4 per million individuals with a carrier rate of 2-4 per million with no sex prediction and no racial predominance, with third of all reported cases having consanguineous parents. The development and eruption of primary and permanent dentition follows the normal chronological order with the normal morphology. Eruption of the dentition into the oral cavity is accompanied by severe gingival inflammation and generalized aggressive periodontitis, in the absence of any local etiologic factors, resulting in tooth mobility and eventual exfoliation of primary dentition by the age of 4-5 years and of the permanent teeth by the age of 13-16 years. There is extensive hyperplastic hemorrhagic gingivitis resulting in periodontal pockets which rapidly deepen, causing severe loss of alveolar bone and marked fetor oris. Even during the most active phase of periodontal destruction, the rest of the oral mucous membrane is reported to be completely normal. Interestingly, after the exfoliation of the permanent dentition, inflammation resolves and gingiva appears healthy and also improvement in skin lesions has been reported.  There have been reports where the third molars remain unaffected and do not exfoliate. A rapid loss of attachment occurs, with the teeth soon lacking osseous support and radiographically appearing to "floating in air appearance" in the soft tissue.  The palmoplantar keratoderma typically has its onset between the ages of 1 and 4 years. Diffuse transgredient (first occurs on the palms and soles and then spreads to the dorsa of the hands and feet) palmarplantar keratosis develops, with occasional reports of diffuse follicular hyperkeratosis and keratosis on the elbows and knees. The lesions are punctate and diffuse, with dry scaly skin and vary in thickness from one to several millimeters. There may be associated hyperhidrosis of the palms and soles, which may cause a foul smell. The keratosis of the plantar surface extends to the edges of the soles and occasionally onto the skin overlying the Achilles tendon, the external malleoli, eyelids, cheeks, labial commissures, legs, thighs, axillae and rarely the trunk. The hair is usually normal but the nails, in advanced cases, may show transverse grooving and fissuring. Histopathological examination reveals nonspecific hyperkeratosis, acanthosis, focal parakeratosis, psoriasiform hyperplasia, tortuous capillaries in dermal papillae and superficial lymphocytic infiltration.  Gorlin et al. have stated presence of third finding in this syndrome- radiographic evidence of calcification of the duramater (intracranial calcification in the choroid plexus and tentorium) marking it as a triad. 
| Case History|| |
A case of three siblings is reported here, with a history of consanguinity of parents. The pregnancy and delivery was uneventful for all the siblings. Phenotypically, the parents were healthy and there was no family history of the disease, suggesting an autosomal recessive pattern of inheritance [Chart 1]. The eldest of the three siblings, a 17-year-old girl (Case-1), reported to the Department of Prosthodontics, complaining of difficulty in chewing due to ill fitting dentures. She has been using these dentures since 6 years. History revealed she was not regularly using dentures for the past 5-6 months, as there was gingival enlargement in the lower left region, with eventual eruption of molar tooth in the region. Her brother a 15-year-old (Case-2), presented with the chief complaint of exfoliation of teeth since 6-7 years. The last sibling a 13-year-old girl (Case-3), reported to Department of Oral and Maxillofacial Surgery, seeking extraction of mobile teeth. History revealed timely eruption of deciduous teeth and their subsequent loss by the age of 4-5 years. Similarly (case 1 and case 2), permanent teeth too were lost prematurely after erupting normally. There had been normal eruption of all permanent teeth (case 3), but gradually her teeth had started becoming mobile. There was a history of recurrent swelling of gums and foul breath followed by loosening and exfoliation of teeth. When the siblings were between 6 and 12 months of age, their parents had noticed thickening of the skin of her hands and feet. Since then there had been a gradually increasing involvement of the palmar and plantar surfaces. On examination, all the siblings had diffuse palmoplantar keratoderma, transgradiens extending up to dorso lateral aspects associated with foul smell; the keratinized skin was clearly demarcated from adjacent normal skin. Deep fissures were present on soles associated with punctate and striate. [Figure 1]a-c. Intraoral and radiographic examination of case 1 revealed completely edentulous maxillary arch and partially edentulous mandibular arch with only left third molar present [Figure 2]a. Premature loss of teeth and loss of alveolar bone had resulted in decreased facial height and a senile appearance in case 1 [Figure 2]b. Case 2 intraoral examination revealed completely edentulous maxillary foundation and mobile premolars in mandibular arch [Figure 3]b, radiographically interpreted as 'floating in air appearance' [Figure 3]a. Case 3 also presented radiographically 'floating in air appearance' [Figure 4]a having missing mandibular incisors and maxillary left second premolar [Figure 4]b. The right maxillary central incisor exhibited marked mobility. The gingiva adjacent to these teeth appeared red, inflamed and edematous, with deep periodontal pockets and associated bleeding. Despite the severity of the periodontal involvement, no local factors (plaque and calculus) were present. The mucosa of the edentulous region was normal.
|Figure 2: Case 1. (a) orthopantomaograph, (b) and (c) before and after esthetic and functional rehabilitation; (d) maxillary complete dentures and mandibular partial dentures|
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|Figure 3: Case 2. (a) orthopantomaograph showing floating in air appearance, (b) intra oral view of mandibular premolars, (c) - maxillary and mandibular complete dentures|
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|Figure 4: Case 3 (a) orthopantomaograph showing 'floating in air appearance', (b) shows partially edentulous dental arches with Grade III mobile 11, (c) after extraction of 11 and Phase 1 periodontal treatment , (d) esthetic and functional rehabilitation of patient with removable partial dentures|
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Past medical history revealed, repeated pyogenic abscess in various parts of body in the eldest sibling (case 1). Case 2 was hospitalized with fever and nonhealing ulcer over the right back region with a draining sinus, 6 years ago, which was diagnosed as pyogenic liver abscess and was treated accordingly. The youngest sibling viz case 3 gave a history of nonhealing ulcer over the right hip, 9 years ago. Therefore, all the family members viz parents and three siblings were given antitubercular treatment for a period of 1 year. As the symptoms did not subside, the antitubercular treatment was discontinued.
The investigations done for all the siblings include radiographs, biochemical, biopsy, ground section of tooth, neutrophil function test (NFT), microbiological and genetic tests. Results of the tests conducted on the patient are summarized in [Table 1].
Considering the present socio economic status of the family, prosthetic rehabilitation with removable dentures was planned. Necessary preventive measures, i.e., scaling and oral prophylaxis therapy with antibiotics for 10 days were accomplished to preserve the remaining teeth and prevent the further resorption of alveolar bone in case 1 and case 3. Dentures were fabricated following the usual steps. Irreversible hydrocolloid (Zelgan 2002, dust free, regular set, Gurgaon, India) impressions were made for partially edentulous cases. Border molding and light body polyvinyl siloxane (Express XT, 3 M ESPE AG, Seefeld, Germany) final impressions made. Case 1 received maxillary complete denture and mandibular removable partial denture resulting in an esthetic and functional rehabilitation of the patient [Figure 2]c,d. Similarly, maxillary and mandibular complete dentures were fabricated for case 2 [Figure 3]c. The third sibling was referred to Department of Periodontics, wherein Phase 1 treatment was done. The maxillary central incisor was eventually extracted as periodontal prognosis was poor [Figure 4]c. Maxillary and mandibular removable partial dentures were fabricated for the last sibling [Figure 4]d. Teeth were selected and contoured to simulate the young permanent dentition. Usual recall schedule and necessary adjustments were done. The siblings' oral health has been regularly monitored for over 24 months. Parents had been informed regarding oral rehabilitation with implants at later stage, which is being presently undertaken. These siblings were also referred to a dermatologist. The treatment involved soaking the extremities in warm salt water twice daily followed by topical retinoid cream application. This dramatically improved the patients' dermatological lesions. Therefore these patients' were not given any oral supplements.
| Discussion|| |
The exact pathogenesis of this syndrome remains relatively obscure. Genetic, immunologic, and microbiologic bases have been proposed.  Recently, two research groups have reported that loss-of-function mutations affecting both the alleles of the cathepsin-C gene, located on chromosome 11q14.1-q14.3, were associated with PLS. It is expressed in epithelial regions commonly affected by PLS such as palms, soles, knees, and keratinized oral gingiva. It is highly expressed in various tissues such as the cells of immune system (polymorphic nuclear leukocytes, alveolar macrophages and their precursors) and in the lungs, kidneys. Its main functions are thought to be protein degradation and proenzyme activation in addition to its immunological role. Mutation in this gene was also detected in a Jewish-Hindu family with Haim-Munk syndrome and prepubertal periodontitis.  A common clinical manifestation in all three syndromes is severe early-onset periodontitis. All PLS patients are homozygous for the same cathepsin-C mutations inherited from a common ancestor, suggesting parental consanguinity. Parents and siblings, heterozygous for cathepsin C mutations do not show either the palmoplantar hyperkeratosis or severe early onset periodontitis characteristic of PLS. Thus Haim-Munk syndrome, prepubertal periondontitis and PLS seem to be allelic variants [Table 2].
Bacteremia during periods of extensive periodontal inflammation associated with the abnormal polymorphonuclear chemotaxis and oxygen consumption are known to occur in PLS patients and likely contribute to the development of the liver abscess. In these siblings, the inflamed gingiva was the likely point of entry of Staphylococcus aureus that led to bacteremia and subsequently the liver abscess (case 2). Pyogenic liver abscess is increasingly recognized as a complication of PLS associated with impairment of the immune system. 
The alkaline phosphatase tests in our three siblings were done as a differential diagnosis for hypophosphatasia. The tests revealed high levels in case 2 and 3, which may be due to the child growth spurt.  This is in contrast to the alkaline phosphatase levels that have been reported in literature. ,
Microbiological studies have demonstrated Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola rganisms, suggesting that many pathogens may be involved in the disease process. Previous case reports and studies have reported that A. actinomycetemcomitans plays a significant role in the pathogenesis and progression of the rapid periodontal breakdown seen in PLS.  This has been attributed to decreased neutrophil phagocytosis, bacterial infection and impaired reactivity to T- and B-cell mitogens. The exact mechanism of the increased susceptibility to infections is also unknown, but some investigators have demonstrated a dysfunction in neutrophil motility and bactericidal function, leading to recurrent pyogenic infections of skin.  The findings of NFT in case 1 are in contrast to the findings of her younger siblings. This can be possibly attributed to absence of the active phase of periodontitis due to loss of all her erupted teeth as the activity of neutrophils is a reversible process.
These various factors contributing to the etiopathogenesis of this disease ensure that successful treatment of the rapid periodontal destruction remains a challenging problem. A multidisciplinary approach is important for the care of patients with PLS. Emollients and 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 before the eruption and maintained during the development of the permanent teeth.. ,,, A course of antibiotics controls the active periodontitis in an effort to preserve the teeth and to prevent bacteremia and subsequently pyogenic liver abscess. The risk of pyogenic liver abscess should be kept in mind in evaluating these patients when they present with fever of unknown origin as reported in Case 2.
| Conclusions|| |
PLS can adversely affect the growing children, psychologically, socially and aesthetically. Hence, 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. A diagnosis of the syndrome by the dentist at an early age, i.e., before the eruption of permanent teeth, can help preserve the teeth by institution of early treatment with retinoids. The primary objective for patients reporting at a later stage with PLS is to treat the devastating periodontitis, by prompt periodontal treatment to preserve disease-free teeth. When such treatment efforts fail, early extraction of teeth with progressive periodontitis will preserve alveolar bone facilitating future prosthodontic rehabilitation, including the use of osseointegrated implants. 
| Acknowledgments|| |
The authors gratefully acknowledge the support and encouragement given by Dr. D. Veerendra Heggade and Dr. C. Bhasker Rao. We wish to thank Dr. Kishore Bhat, Microbiologist, and Dr. Rachana Sampth Kumar, Dermatologist for their valuable inputs; Dr. K. Gopal Krishnan, Dr. Lekha, Dr. Roseline, Dr. Ranjit, for their timely advice and contribution. The authors acknowledge Mr. Madhu Kadam for his assistance in photography.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]