Papillon-Lefevre syndrome: A case report of 2 affected siblings.

Papillon-Lefèvre syndrome (PLS) is a very rare syndrome of autosomal recessive inheritance characterized by palmar-plantar hyperkeratosis and early onset periodontitis, leading to premature loss of both primary and permanent dentitions. Various etiopathogenic factors are associated with the syndrome, but a recent report has suggested that the condition is linked to x mutations of the cathepsin C gene. The purpose of this report is to describe two cases of PLS in the same family who presented to the Department of Dentistry of Dr. R. P. Government Medical College at Tanda, Kangra (Himachal Pradesh) with a chief complaint of mobility and rapid loss of teeth. Hyperkeratosis of palms and soles was present. On intraoral examination, there was severe gingival inflammation, abscess formation, and deep periodontal pockets with mobility of teeth. Histopathological examination of the specimen taken from the thickened skin was reported to be consistent with PLS. The dental treatment comprised oral prophylaxis, scaling and root planning, antibiotic therapy, instructions on oral hygiene, restorations, extraction of hopelessly affected teeth, and prosthetic rehabilitation.

INTRODUCTION

The Papillon-Lefèvre syndrome (PLS) was first described by Papillon and Lefèvre in 1924.[1] PLS is an autosomal recessive disorder that is caused by mutations in cathepsin C (CTSC). PLS is characterized by palmoplantar hyperkeratosis and aggressive periodontitis has a world-wide prevalence of 1-4 cases per million in the general population and is often related with consanguinity.[123]

Dermatological disorders initiate with erythema and after about 6 months, they progress to hyperkeratosis of soles, palms, knees, and elbows.[4] This exacerbates in winter, leading to painful fissures. Aggressive periodontitis begins with the primary dentition, leading to periodontium destruction, and the premature loss of deciduous teeth by age of 6 years; afterwards gums heal, until the development of the permanent dentition, when periodontitis reappears and teeth are prematurely lost by the age of 16 years.[5] Besides these basic features, PLS patients can present with liver abscesses,[6789] increased incidence of pyogenic infections[10] or mental retardation.[11] Medication for hyperkeratosis and periodontal care improve the quality of life.[1213]

The CTSC gene (11q14.2) spans 4.7 kb and has seven exons.[1415] CTSC gene mutations have been reported as responsible for PLS[14] as well as similar conditions such as Haims-Munk Syndrome, and juvenile periodontitis.[1617] CTSC is expressed at high levels in polymorphonuclear leukocytes, alveolar macrophages, skin, kidney, and placenta, and at moderate or low levels in a variety of other organs.

CTSC (EC 3.4.14.1) or dipeptidyl peptidase I is a lysosomal cysteine protease that removes dipeptides from the free N-termini of protein and peptides. CTSC plays a significant role in the cleavage of some hormones (including glucagon, gastrin and angiotensin II), and activation of granule serine proteases from cytotoxic T lymphocytes, natural killer cells (granzymes A and B), mast cells (tryptase and chymase), and neutrophils (cathepsin G and elastase).[18]

CTSC deficiency has been associated with PLS-associated increased susceptibility to bacterial infection in gums and other sites; however, the heterogeneous severity of the periodontitis and susceptibility to infections observed in PLS suggests the existence of compensatory pathways in most tissues.[19] The PLS phenotype also suggests a role for CTSC in epithelial differentiation or desquamation. Several works have shown a relationship between CTSC and the development of gingival fibroblasts, and peeling of skin keratin in affected zones.[20] Aberrant epithelial differentiation may affect the junctional epithelium that binds the gingiva to the tooth surface, possibly weakening this mechanical barrier and allowing deeper colonization by periodontal pathogens.[20]

Various approaches for treating the periodontal condition associated with PLS have been reported. These include oral hygiene instruction, use of mouth rinses, frequent debridement, multiple antibiotic regimens, periodontal surgery, extraction of hopeless teeth, and extraction of all primary teeth.[21]

CASE REPORTS

A 16-year-old boy (case 1) presented to the Department of Dentistry, DR. R. P. Government Medical College, Kangra at Tanda, Himachal Pradesh with the chief complaint of loose teeth and markedly inflamed gingiva, with excessive bleeding and severe halitosis. The patient was referred to our Department for general dental care by the Department of Dermatology where he had been diagnosed with PLS. An overview of the medical history revealed that, by the time the patient came to our department, he was following a therapeutic routine with oral administration of etretinate (Tegison, 10 mg three times daily for 4 weeks) for treatment of PLS dermatologic manifestations. Typical clinical signs of the disease were seen during the child's 1st year of life. However, he had not sought any treatment until now. The patient had one younger female sibling, 11-year-old girl (case 2) who also showed trait of PLS.

General and extra-oral examination

On general examination, the patients were moderately built with a steady gait. The physical and mental development was also normal. The family history revealed consanguineous marriage of the parents. The parents and other family members were not affected.

Medical history was non-contributory. Mother had a full term normal uneventful pregnancy. Natal history revealed that the patients 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 6 months of age, which gradually thickened and became rough and scaly. These symptoms were worse during the winter season.

Dermatological examination revealed increased keratinization of the skin of the palmar and plantar surfaces as well as the skin over the dorsal surfaces of the joints of the hands; the keratinized skin was clearly demarcated from adjacent normal skin [Figure 1]. Deep fissures were present on the soles of feet [Figure 2]. His nails and hair were normal. Patient had a reduced facial height due to resorption of the alveolar ridge.

Figure 1

Case 1 - Hyperkeratosis of skin over palms

Figure 2

Case 1 - Hyperkeratosis of skin over soles with deep fissures

The past dental history revealed that the deciduous teeth had erupted normally, but there had been early shedding, starting at age of 3 years and complete shedding of all deciduous teeth by the age of 6 years. The mother reported that all of the patient's primary teeth were prematurely lost due to hypermobility. There had been normal eruption of all permanent teeth, but gradually the teeth had started becoming mobile and this was followed by exfoliation of the teeth and also described gingival bleeding during brushing and eating, after the eruption of permanent teeth.

Intraoral examination

Case 1

A 16-year-old boy had permanent dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets. Severe mobility affecting most of the teeth, with heavy deposits of plaque and calculus and halitosis were also present [Figure 3].

Figure 3

Case 1 - Intraoral view of dentition

The patient was found to be completely edentulous in the mandibular right quadrant. In the other quadrants, the permanent teeth that were missing were the right maxillary first molar, the right maxillary first premolar and second premolar, the lateral incisors, the central incisors, the left maxillary second premolar [Figures 4 and 5]. All the permanent teeth that were present exhibited marked mobility. The gingiva adjacent to the teeth appeared red, inflamed and edematous. There was bleeding on probing with deep periodontal pockets. Gingival recession was present in all the teeth. The mucosa of the edentulous area appeared normal.

Figure 4

Case 1 - Intraoral view of maxillary teeth

Figure 5

Case 1 - Intraoral view of mandibular teeth

The radiographic examination using panoramic film showed extensive bone loss and areas suggestive of vertical defects [Figure 6].

Figure 6

Case 1 - Panoramic radiograph showing extensive bone loss

Case 2

An 11-year-old girl, younger sibling, had mixed dentition with severe gingival inflammation, abscess formation, and deep periodontal pockets [Figure 7]. Severe mobility affecting most of the teeth with halitosis were present. The radiographic examination using panoramic and periapical films showed severe alveolar bone loss up to the apical third region of the roots of the permanent teeth that were present, giving them the characteristic “floating-teeth” appearance [Figures 8 and 9].

Figure 7

Case 2 - Intraoral view of maxillary and mandibular teeth

Figure 8

Case 2 - Panoramic radiograph showing severe bone loss

Figure 9

Case 2 - Periapical radiograph showing floating in air appearance of teeth

On lateral cephalogram, there was no evidence of intracranial calcification in both patients. Laboratory investigation was carried out, which included hematological and biochemical assessment.

Routine blood investigations and liver function tests were found to be within the normative range of values.

Management

The dental treatment comprised involved a professional prophylaxis, scaling and root planning, basic instructions on oral hygiene and use of 0.12% Chlorhexidine mouth rinse. The carious teeth were restored and hopeless teeth with severe bone loss were extracted. The patient was simultaneously placed on an antibiotic regimen of amoxicillin capsules (250 mg) and metronidazole tablets (200 mg) each three times a day for 8 days. Thereafter, patient started on periodically scheduled appointments for periodontal therapy and instructions on oral health-care were rein-forced at each session. The combination of periodontal debridement and antibiotic therapy was intensified. Throughout the 1 year treatment, the patient was prescribed several repeated courses of amoxicillin capsules (250 mg) and metronidazole tablets (200 mg) each three times a day for 8 days. Due to progressive generalized bone loss; interim removable partial dentures were given. The patient returned for follow-up visits once in 3 months. New impressions were made and removable partial dentures were inserted, with supportive periodontal therapy and antibiotic coverage [Figure 10a and b]. There has been no evidence of progression of the disease, such as acceleration of residual ridge resorption. In general, the dentures have been well-tolerated and no relevant clinical issues have arisen. The parents were instructed to bring the patient to our service in case adjustments were needed or any other unexpected problem with the prostheses arose between the scheduled treatment appointments.

Figure 10

(a) Case 1 - Prosthetic rehabilitation with removable partial dentures; (b) Case 1 - Complete prosthetic rehabilitation

DISCUSSION

PLS can adversely affect growing children psychologically, socially, and aesthetically.

Typically the parents are not affected and there is no family history of the disease.

Higher prevalence has been reported when parental consanguinity is involved, but no predilection for gender or race has been documented.[2122] The patient in this case report was a male, his parents were consanguineously related and the disease affected one of the siblings. The two cases reported here were associated with consanguinity of parents. Phenotypically, the parents were healthy and there was no family history of the disease, suggesting an autosomal recessive pattern of inheritance.

The typical clinical features of PLS include palmar-plantar hyperkeratosis and generalized aggressive periodontitis accompanied by severe alveolar bone destruction, leading to early loss of both primary and permanent dentitions. The clinical manifestations observed in our patient were hyperkeratosis of the palms, soles, elbows, and knees and generalized aggressive periodontitis, which resulted in loss of the primary and permanent teeth. Because the etiology and pathogenesis of PLS periodontitis is directly related to high levels of Actinobacillus actinomycetemcomitans, the use of an antibiotic that acts specifically on this pathogen has been claimed to be important for a successful treatment.[23] Some authors have recommended the elimination of periodontal pathogenic flora through premature extraction of all primary teeth combined with antibiotic coverage in an attempt to minimize the possibility of infection of the unerupted permanent dentition.[24] Selecting the ideal treatment is not as clear-cut when the patient seeks dental care in the mixed dentition stage or later. In these patients, the treatment plan may include either extraction of all erupted teeth followed by a period of antibiotic coverage[25] or extraction of only the hopelessly affected teeth combined with periodontal therapy for the remaining teeth with antibiotic coverage.[26] Studies have shown that the combination of intensive periodontal treatment and antibiotic regimen only temporarily delayed the progression of periodontal disease and did not prevent loss of both primary and permanent teeth. The outcome of the long-term follow-up case report showed that management of PLS-associated periodontitis is further complicated when the patient is first seen in the mixed dentition stage or later. The prognosis of controlling periodontal breakdown progression and minimizing tooth loss are poor.[27]

Although the results of laboratory tests in patients with this syndrome are all essentially within normal limits, they are nonetheless particularly valuable in distinguishing this syndrome from other conditions causing gingival inflammation and early loss of the deciduous and/or permanent teeth, such as leukocyte imbalances (neutropenia and leukemia), mercury and radiation toxicities, acatalasia, hypophosphatasia, Hand-Schuller-Christian disease, Letterer-Siwe disease, and the periodontitis of juvenile diabetes and periodontosis.[2223] 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. It would provide immediate satisfaction to the patient in terms of esthetics and function.[28] In the present case, prosthetic rehabilitation was considered in order to provide immediate satisfaction to the patient in terms of esthetics and function.

CONCLUSION

It is important that dental professionals be familiar with the etiology of PLS, as well as with PLS-specific dermatologic manifestations and periodontal involvement, to be able to identify the disease in its very early stages. Early diagnosis of PLS-associated periodontitis and institution of an appropriate periodontal/antimicrobial treatment regimen might improve the prognosis for the dentition. The recommendation is that young patients with skin lesions and severe periodontal destruction together with premature loss of teeth should be referred to a periodontist as early as possible. This should prevent or delay tooth loss and enhance early replacement of missing teeth for preservation of function and esthetics. In conclusion, successful periodontal management of PLS patients remains challenging. However, as our understanding of the etiological factors increases, it is hoped that successful treatment strategies will be developed. Further, investigations and additional clinical-based data are required to substantiate this assumption.