Full or partial edentulism in children and adolescents occurs most commonly as a result of trauma or genetic disorders, and these patients encounter esthetic and functional problems ¹ . Esthetic problems can cause psychologic disorders and affect social activity ^1,2 . Long-standing edentulism leads to a senile profile and a decreased facial height ³ . The functional problems experienced include difficulty in eating and speaking ^1,2 . Papillon–Lefèvre syndrome (PLS; OMIM#245000) is one of the disorders that can cause early tooth loss ^3,4 , and those affected by PLS usually need oral rehabilitation to overcome these problems ³ .

PLS is a rare autosomal recessive disorder with dermal and oral manifestations ^4,5 . Mutation in the cathepsin C gene (CTSC), which is localized on chromosome 11q14-q21, in these patients causes the loss of cathepsin C function. Cathepsin C plays a role in epithelial differentiation and desquamation ⁶ . The severity of dermal manifestations, including diffuse hyperkeratosis affecting the palms of the hands and soles of the feet, varies in patients from mild psoriasiform scaly skin to overt hyperkeratosis ^4,5 . The soles of the feet are usually affected more than the palms, and the degree of hyperkeratosis may be affected by seasonal changes. There is evidence that the hyperkeratosis severity is associated with periodontal involvement ⁵ . PLS patients’ neutrophil functions are affected, and these dysfunctions appear to be localized to tissues that are under direct and chronic bacterial attacks like the periodontal tissue. This has been suggested to be the possible reason for PLS patients’ lack of systemic infections ⁷ .

Rapid progressive destructive periodontitis around primary and permanent dentitions is the oral manifestation of PLS ⁸ . The inflammatory gingival changes and periodontitis around primary dentition appear concomitant with palmoplantar keratosis and subside after tooth loss ⁵ . Because of this, almost all PLS patients lose their teeth at a young age. Surprisingly, third molars, which erupt at older ages, are not affected ^3,5 . PLS patients’ immune system function improves with age and their polymorphonuclear (PMN) cells’ chemotaxis and phagocytosis abilities become normal after some years of being edentulous ^8,9 .

Dental implants can be a viable treatment option for these patients in order to overcome esthetic and functional prosthetic problems ¹⁰ . However, issues surrounding implantation raise success concerns in these patients; these issues include impaired patient immune systems and severe bone loss that results in the need for complex ridge augmentations ^10,11 . The aim of this systematic review was to assess the clinical outcome and the survival rate of dental implants used for the oral rehabilitation of PLS patients.

The present study is a systematic review that was performed in accordance with the “Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols” (PRISMA-P, 2015)¹². The search was performed using “MeSH” terms and keywords based on the elements of the PICO question:

The primary electronic search resulted in 80 studies. After exclusion of irrelevant studies, 11 articles with 15 cases were included in this systematic review.(Table 1) These cases included six male and nine female patients afflicted by PLS who were treated by dental implants. The mean age of patients at the time of implant placement was 20.69±4.96 years, and most of implant placement was done after the age 18. A total number of 136 dental implant placements were reported for these patients. Most of the treatment plans called for full mouth rehabilitation followed by mandibular overdenture. One case reported two single implant placements of maxillary central incisors, the only maxillary teeth lost. The patient was under meticulous follow-up before and during permanent teeth eruption. Her mandibular incisors were planned for future reconstruction³.

Peri-implantitis was reported in three patients with poor oral hygiene, and a total of 20 dental implants failed (14.70%). Implant failures occurred in three patients, and these rates were obtained without considering the replaced implants. The reasons of implant failure were peri-implantitis (2 patients) and lack of osseointegration (1 patient). Gingival hyperplasia around one implant due to lack of attached gingiva was reported. The failure rate was higher in maxillae. Meta-analysis of the probability of failure was 7% (95% confidence interval [CI] 0%-31%) for maxillary implants and 2% (95% CI 0%-9%) for mandibular implants. The value of I² was 73% and 0% for maxillary and mandibular implants, respectively. The overall result for all I² was 50.81% with a pooled random effect estimate of 3% (95% CI 0%-12%). A forest plot of the meta-analysis is provided in Fig. 2. None of the patients had healing problems after the placement of implants or bone graft. The mean and median follow-up after prosthetic rehabilitation was 5.16±5.08 years and 4 years (Q1=1, Q2=8.75), respectively. The follow-up time ranged between 1 years and 20 years.

Periodontitis is an important manifestation of PLS and, in these patients, the conventional periodontal treatments usually cannot prevent the progressive attachment loss ^8,14 . In addition to periodontal treatment, antimicrobial therapies including erythromycin, tetracycline, penicillin, and amoxicillin-metronidazole have been suggested. However, controversial results have been reported ¹⁵ . Continuous attachment and tooth loss are present in some patients ^11,14 . These patients experience partial or complete edentulism during their adolescence ⁸ and need oral reconstruction. Conventional complete denture or overdenture is the traditional prosthetic treatment for PLS patients, but this treatment causes esthetic and functional problems that lead patients to seek a more comprehensive treatment ¹⁰ . The chief patient complaints were the lack of stability and retention of their mandibular prosthesis8,16-18. Dental implants can provide the necessary support, stability, and retention for dental prostheses ¹⁰ and are, therefore, helpful to PLS patients. The benefits of implants include not only enhanced prosthesis stability and retention, but also preservation of the supporting bone and prevention of further bone loss ⁸ .

Extraction of all PLS patient primary teeth so that the patient experiences an edentulism period between primary and permanent dentition has been reported to be helpful ^9,14,19 .

Although implants help patients with edentulism, lack of available bone for dental implant placement as the result of progressive periodontitis and/or continuous use of full dentures for many years is the major problem for these patients ^10,17,18 .Therefore, an implant-based treatment plan for these patients is, in many cases, restricted to overdentures unless complicated pre-surgical bone augmentations are required ¹⁰ . In this review, pre-surgical augmentation was reported in three patients. These included sinus augmentation, inferior alveolar nerve repositioning and guided bone regeneration (GBR) using extra-oral harvesting bone (calvaria and tibia) or bone substitute material ^3,10,20 . Simultaneous GBR was also performed during implant placement if needed ²¹ . In all cases with bone augmentation, the healing period was normal and uneventful ^3,10,20,21 .

To avoid these complicated and expensive procedures, implant placement between the mental foramina for fixed mandibular prosthesis could be the treatment of choice if sufficient bone is available in the anterior mandible ^8,22 . Insertion of two implants in the anterior mandible was another treatment modality for an implant-supported removable overdenture ^17,18,23 . Etöz et al. ¹⁷ used short dental implants for mandibular overdenture support. Their patient showed severe ridge atrophy so distraction osteogenesis had a potential for bone fracture ¹⁷ .

Osseointegration occurred successfully except for the early failure of one implant. For areas lacking soft and hard tissue, distraction osteogenesis is suggested ³ .

Another consideration for PLS patients is the age at edentulism. Most of the patients lost their teeth early; these patients lost most of their permanent teeth by 14 years ⁵ . However, dental implants act as ankylosed teeth and are contraindicated in teenagers and growing individuals ²⁴ . Dental implants inserted in patients under the age of 18 led to infra-occlusal positioning of the maxillary dental implant. Insertion of dental implants in the anterior mandible encountered less complications ¹ . Ullbro et al. ⁸ suggested that dental implant complications in growing PLS patients was less important than bone preservation. Bohner et al. ¹ suggested that, whenever growing patients may benefit more from dental implants, the implantation can be performed cautiously; maintenance follow-ups and implant-supported prosthesis adjustments are required until growth cessation. However, in their systematic review only anterior region implant placements were considered ¹ . Dental implant placement before the cessation of growth had been performed in patients with ectodermal dysplasia. A systematic review ²⁵ demonstrated that the rate of dental implants failure in these patients was relatively low (5.3%-7.2%).

Impaired immune systems of young PLS patients is another consideration ¹¹ . PLS patient neutrophils are deficient in the ability to establish neutrophil extracellular traps (NET), and chemotactic velocity is also reduced in PLS patient neutrophils ⁷ . However, clinical evaluation and long-term follow-up of PLS patients have shown that the function of PMNs in PLS patients improves with age ^8,9 . Tinanoff et al. ⁹ reported normal PMN chemotaxis and adherence in their patient after 15 years follow-up (at age 24 years). Ullbro et al. ⁸ tested the PMN chemotaxis and phagocytosis of their patient before implant placement (at age 25 years) which had improved to normal values. Therefore, the insertion of PLS patient dental implants at younger ages may result in the same inflammatory process as the one that occurs in the teeth. Based on these articles, the optimum age for implant placement in PLS patients is still unclear; and, if implant treatment is performed at an early age, immunological analysis is necessary. Most of the cases in this review received dental implant treatment after the age of 18.

This systematic review assessed the results of dental implant treatment in PLS patients. The longest follow-up periods after implant placement reported in these studies were 20 years and 10 years ¹¹ . Other extended follow-up periods included 9 years ²² , 4.5 years ⁸ , and 4 years ^10,11 . In 40% of patients the implant follow-up time was 2 years or less.

Peri-implantitis occurred in three patients. Implant failure (19 implants) resulted in two of these patients. Poor oral hygiene and poor compliance with the maintenance program were reported as a probable cause of implant failure. Another implant failure occurred due to lack of osseointegration; implant replacement was successful. One implant showed gingival hyperplasia due to lack of attached gingiva. Poor oral hygiene and lack of regular attendance at recall visits were reported as important factors in occurrence of peri-implant diseases26-28. These results emphasize that oral hygiene and compliance with follow-up programs have important roles in PLS patient implant success. The results of this study showed a higher rate of maxillary peri-implantitis and implant failure.(Table 1, Fig. 2) The data concerning the higher prevalence of maxillary peri-implantitis was heterogeneous and this relationship was not proven ²⁹ .

More cases with long-term follow-up results are required for drawing definite conclusions about dental implant treatment modalities in PLS patients.