Ⅰ. Introduction

Dental implants have been proven to be a reliable treatment strategy to reconstruct edentulous areas with reliable clinical outcomes.^{1, 2} However, excellent results of high success and survival rates have mostly been observed in patients without local or systemic problems that might harm the healing process, and there have been other risk factors such as smoking and uncontrolled diabetes that might harm implant survival.³ Peri-implantitis, which is characterized by an inflammatory response in the connective tissue and progressive bone loss around the implant resulting in subsequent implant failure, might be associated with risk factors, including poor oral hygiene, smoking, and a history of periodontitis.⁴

The predictability of clinical results can be affected by bone quality and quantity,⁵ but more recently, soft tissue around implants is being focused on because of its importance in maintaining peri-implant health.⁶ Peri-implant mucosa has different anatomical features compared to those found around natural teeth, as the peri-implant connective tissue fibers are parallel to the surface without direct attachment, the vascular supply is reduced, and the junctional epithelium is more permeable with fewer fibroblasts and greater collagen fibers in the connective tissue compartment. These aspects render the implants more susceptible to inflammation and microbial challenge.^{7, 8}

Oral lichen planus (OLP) is characterized by a chronic inflammatory disease of the mucosa, which results in damage to the epithelium and connective tissue. As a mucosal disease, OLP was suggested to have a negative effect on the attachment of epithelium to implant prosthetic surface.⁹ In the past, dental implants were not recommended in patients with OLP due to the possibility of painful inflammation traumas such as oral mucositis that might be associated with implant failure.¹⁰

To date, there is no consensus regarding the benefits and disadvantages of implant treatment in patients with OLP, although the spectrum of indications has widened. To plan dental implants in patients with OLP, clinical outcomes and complications should be further investigated. Therefore, this study aimed to evaluate the survival rate of dental implants in patients with OLP through a literature review.

Ⅱ. Materials and Methods

1. Search Strategy

Published literatures up to 2022 were searched from the database of PubMed/Medline, Cochrane, Web of Science and Scopus with the keywords, “lichen planus,” “oral lichen planus,” “implant,” “dental implant,” and “peri-implantitis,” used alone or in combination by “OR” and “AND.” The complete text of English case reports, case series, case-control studies, randomized clinical trials (RCTs), retrospective studies, cross-sectional studies, and prospective studies on dental implants used in patients with OLP were included. In vitro and in vivo studies and abstracts were excluded.

2. Clinical Features of Oral Lichen Planus

OLP is clinically characterized by intersections of white lines or striae (Wickham’s striae) on a varied range of erythematous surroundings and distributed symmetrically.^{11, 12} It affects the buccal mucosa, gingiva, and tongue as oral lesions, and expressed as six patterns including reticular, atrophic, erosive, popular, plaque and bullous subtypes.¹³ The prevalence of OLP is up to 1.01% worldwide and occurs more frequently in women between 40 and 60 years of age.¹⁴ A minority of patients with OLP show disease expression concurrently including the cutaneous, penial, vulvo-vaginal, esophageal, and conjunctivae regions. Patients with OLP might experience discomfort upon contact with spicy or acidic foods, mucosal roughness, or stiffness.^{11, 12} Erosive and atrophic subtypes are known to be mostly symptomatic, and gingival lesions of OLP represent desquamation, bleeding, and ulcerations.¹⁵

3. Etiology, Pathogenesis and Histopathologic Features

OLP is an autoimmune and chronic inflammatory disease. Although the etiology is unknown, some contributing factors of OLP have been suggested, including psychological stress,¹⁶ genetic background,¹⁷ systemic associations such as hepatitis C virus,¹⁸ and thyroid dysfunction.¹⁹ In addition, oral lichenoid reactions are considered as variants of OLP or a disease by itself, which are associated with systemic drug intake and dental materials.²⁰ OLP has been known to be involved with T cell-mediated immune dysregulation to unknown antigenic changes in predisposed patients, which result in the increase of TNF-α, IFN-γ and keratinocyte/T cell/antigen-presenting cell associations.²¹ Increased production of T-helper 1 (Th1) cytokines, TNF-α, and IFN-γ is the key early event in OLP;^{22, 23} however, recent studies have reported the potential contribution of Th2-mediated inflammation in the pathogenesis.²⁴ The malignant potential of OLP is controversial, although a few studies have reported a higher risk of transformation to squamous cell carcinoma.²⁵

Microscopic appearances of OLP show hyperparakeratosis and/or hyperorthokeratosis, cytoid bodies (Civatte bodies), hydropic changes in basal cells, and band-like lymphocytic infiltration in the lamina propria.²⁶ This inflammatory change of interface mucositis can also be observed in other oral lesions, such as oral lichenoid conditions and lupus erythematosus. Sawtooth rete ridges or atrophy at the epithelium-connective tissue junction, ulceration, and acanthosis can also be found.

4. Diagnosis of Oral Lichen Planus

Diagnosis of OLP is challenging, as the clinical and histopathological features can overlap with other oral lichenoid lesions, including mucous membrane pemphigoid, chronic ulcerative stomatitis, and lupus erythematosus.²⁷ Further investigations, such as direct immunofluorescence (DIF), may be used as a diagnostic adjunct to differentiate OLP from other autoimmune blistering diseases that present with desquamative gingivitis. OLP is characterized by fibrinogen deposits along the epithelial basement membrane zone without immunoglobulin or complement; however, it can also be found in premalignant and malignant lesions.^{28, 29} For DIF, frozen sections of fresh tissue or an adequate transport medium (Michel’s solution) are required. A set of diagnostic criteria was suggested in a position paper by the American Academy of Oral and Maxillofacial Pathology, from which a more homogenous OLP patient group can be expected for future research and diagnostic accuracy (Table 1).³⁰

Ⅲ. Results

Thirteen studies reporting the survival rates of dental implants in patients with OLP that met the inclusion criteria were included in this review. The data were extracted to describe the study type, number of implants and patients enrolled in the study, type of implant and restoration if available, follow-up periods in months, and survival rates, as described in Tables 2 and 3.

1. Survival rate of Implants in Patients with Oral Lichen Planus

1) Case reports

Among the reviewed literature, seven case reports were included (Table 2). All OLP cases were from female patients who mostly showed clinical features of erosive-type OLP and other types such as reticular, atrophic, or mixed. The survival rate of dental implants in patients with OLP were 100%, with the follow-up ranging from 12 to 96.3 months.^{31, 32, 33, 34, 35, 36, 37}Overdenture, fixed complete, and partial prostheses were all introduced in the case reports. In a case report, Esposito et al.³¹ described that the bone quality and parafunction were related to implant failure rather than to the presence of OLP itself. A few case reports have described oral squamous cell carcinoma that occurred around the implants,^{33, 34} and loss of implants due to mandibular resection together with the implant was reported in one study.³⁴ However, osseointegration was still intact. The malignant transformation of OLP is controversial and should be carefully considered.

2) Retrospective studies

Four retrospective case-control studies with both female and male patients were reviewed (Table 3).^{38, 39, 40, 41}Czerninski et al.³⁸ compared the clinical manifestations of OLP between patients treated with implants (study group) and those without implants (control group). Demographic profiles showed a female predilection for patients with OLP, and 54 implants in 14 patients were included in the study group. Both groups were treated with potent topical steroids (dexamethasone 0.4%/triamcinolone 8 mg or clobetasol propionate ointment 0.05%) once or twice daily from the initial treatment for no more than 2 weeks. The implants were placed 6 months to 10 years before the first visit, and none of the implants failed during the follow-up periods of 12-24 months. Clinical findings, including the type of OLP, distribution of lesions, patient-reported parameters, and patient complaints, did not show significant differences between the groups. In a case-control cross-sectional study reported by López-Jornet et al.,³⁹ three groups of 16 patients were divided as follows: Group I, who received implants and were diagnosed with OLP; Group II, who were diagnosed with OLP but had no implants; and Group III, who had implants but no OLP. The implant survival rate was 96.42% in Group I during the 42 (12–120) months of follow-up and 92% in Group III during the 48 (24–48) months, with an insignificant difference among the groups. However, oral quality of life was significantly better in patients without OLP. In a single-cohort retrospective study by Anitua et al.⁴⁰, treatment consisted of deflazacort 30 mg two days prior to implant placement, 15 mg for three days and 7.5 mg for another three days postoperatively was used to avoid flare-ups of OLP in patients who received short implants less than 8.5 mm. The success rate was 98.4% during 68 months of follow-up with adequate management of OLP. In a retrospective study by Khamis et al.,⁴¹ 59 patients were divided into three groups: implants placed in controlled OLP by low-dose systemic corticosteroids (dose of 4 mg/48 hours), healthy individuals without OLP, and patients with non-controlled OLP who stopped medication 12 weeks after the placement. None of the implants failed at the 4-year follow-up; however, marginal bone loss in the non-controlled group was significantly increased (2.53 mm; p < .001), whereas the remaining two groups showed no differences. The interaction between the disease state and evaluation or observation time was significant. Histopathological features from the biopsies revealed inflammatory cell infiltration and tissue destruction in noncontrolled group. The results demonstrate that OLP should be controlled with low-dose corticosteroids in patients undergoing implant placement to prevent increased marginal bone loss and reduce clinical manifestations.

3) Prospective studies

In a prospective controlled study by Hernández et al.,⁴² two groups were evaluated: OLP patients with 56 implants and healthy control patients with 62 implants. The implant survival rate was 100% in a mean follow-up of 53.5 months in the OLP group and 96.7% in 52.3 months in the control group, with no significant difference between the groups. Complications immediately after surgery, including pain and wound healing, were similar between the groups. Implant placement was avoided during the erosive phase, and the recurrent lesion was treated with 0.05% clobetasol propionate solution three times daily. Aboushelib and Elsafi proposed a treatment protocol for patients with active lichen planus receiving implants in a prospective study.⁴³ Twenty-three patients diagnosed with active OLP underwent implant placement, and 42 out of 55 implants failed within a short loading time of 7 to 11 weeks. After the removal of failed implants, patients were treated with an ascending dose (5 mg/10 days) of oral corticosteroids until a daily dose of 20 mg/day was reached, which was maintained for 2 weeks. Low-energy soft tissue laser irradiation was additionally used, and a new set of 42 implants were placed after 8 weeks. All newly placed implants were functional after 3 years of follow-up. CD8 cell count and inflammatory cell infiltration at the epithelial soft tissue interface in the biopsy specimen were reduced during corticosteroid and laser treatment, and the marginal bone level was maintained, although there was an initial reduction 3 months after loading. The report also concluded that active OLP should be managed before implant placement.

4) Biologic complications

Among the literature reviewed above, two studies evaluated the incidence of peri-implant mucositis and peri-implantitis along with survival rates. In a case-control cross-sectional study, López-Jornet et al.³⁹ reported 17.86% peri-implant mucositis and 25% peri-implantitis in the OLP group during 42 (12–120) months, and 18% and 16%, respectively, in implants in the control group during 48 (24–48) months. The reticular type was frequently found, but without a significant difference between the two OLP groups, and 43.75% of the OLP patients with implants received topical corticosteroids (0.01% triamcinolone acetonide) three times daily. The study reported that OLP was not a risk factor for peri-implantitis with an odds ratio of 1.32 and a 95% CI (0.81–2.41) (p = .257). In a prospective controlled study by Hernández et al.,⁴² peri-implant mucositis was observed in 44.6% of the implants and 66.7% of the patients, and peri-implantitis was observed in 10.7% of the implants and 27.7% of the patients, with no significant difference compared to the control group. A statistically significant association between desquamative gingivitis and peri-implant mucositis was observed in the OLP group when the implant was used as the analysis unit (p = .004).

Ⅳ. Discussion

OLP is characterized by a chronic inflammatory mucosal disease and T cell-mediated immune dysregulation. A local increase in pro-inflammatory cytokine levels and changes in the expression of molecules for cell adhesion in OLP have been reported.⁴⁴ Moreover, OLP has been suggested to have a negative effect on epithelial attachment to the titanium surface, which postulates the possibility of different responses to bacterial challenge and faster breakdown of peri-implant soft tissue seal compared to the healthy mucosal condition.^{9, 45} Therefore, it could be questioned whether to select implant placement as a therapeutic strategy for patients with OLP, and the reviews on clinical outcomes, including survival rate and complications, might help clinicians make decisions for optimal treatment plans.

Results from the retrospective and prospective studies showed an average survival rate of 99.1 ± 1.5% for implants placed in patients with OLP during a mean follow-up period of 45 ± 15 months, and 97.2 ± 3.8% during 43 ± 13 months for implants in the control group with a healthy state, and the studies reported no significant difference between the two groups. Implant placement was avoided during flare-up periods with an active OLP state, and remission of the atrophic- or erosive-type was achieved before surgery. Topical and systemic corticosteroids with various ingredients and treatment protocols were introduced throughout this study. For instance, topical steroids such as 0.01% triamcinolone acetonide three times a day³⁸ or 0.05% clobetasol propionate solution⁴² were used in each study. Czerninski et al.³⁸ used dexamethasone 0.4%, triamcinolone 8 mg, or 0.05% clobetasol propionate ointment applied once or twice a day for 2 weeks as the initial treatment. Anitua et al.⁴⁰ used deflazacort 30 mg two days prior to implant placement, 15 mg for three days and 7.5 mg for another three days postoperatively to prevent flare-ups. Aboushelib and Elsafi⁴³ reported an extremely high failure rate for implants placed in patients with active lesions without prior medication, which were then successfully placed after oral corticosteroid administration and low-energy soft tissue laser irradiation. However, the study did not include control groups, and it was difficult to determine whether other factors were involved in the results. Roles of CD8 and T-cell expression, down-regulation of IL-10 and increased expression of TNF-α found in the OLP lesion have been studied to understand the process that disrupt the immune balance and bone homeosis.^{46, 47} There is still a lack of information about the biological mechanisms or effects of OLP on osseointegration and further investigations are necessary in this field.

Two studies reported the prevalence of peri-implant mucositis and peri-implantitis, which were 17.86% and 44.6% for peri-implant mucositis and 10.7% and 25% for peri-implantitis in patients with OLP.^{39, 42} Different results could be explained by the case definitions, prosthetic designs, treatment protocols, and maintenance care applied in each study. Both studies demonstrated that the prevalence of each peri-implant disease was similar to that in a control group with a healthy gingival condition. Implant placement did not negatively affect the clinical course of OLP and OLP was not a risk factor for peri-implantitis. However, patients with erosive OLP and desquamative gingivitis exhibit a higher rate of peri-implant mucositis.⁴²

There is still no consensus on the treatment guidelines for active OLP. Most patients use topically or systemically administered corticosteroids, as mentioned above. A recent systematic review proposed a protocol for OLP treatment with some important remarks.⁴⁸ Biopsy to confirm the OLP diagnosis, avoidance of a flare-up period with active OLP, implant treatment in the remission phase, prophylactic corticosteroid administration, meticulous oral hygiene, and regular frequent appointments to prevent inflammatory tissue response and to detect malignancy should all be considered before planning implant placement in patients with OLP.

The present literature review has limitations in that the majority of the studies included were case reports and retrospective studies with biased results and incomplete data. Studies with larger sample sizes, longer follow-up periods, well-designed prospective studies, and case-control studies should be conducted. Biopsies for histopathological information should also be considered in the study of OLP to improve diagnosis.

Ⅴ. Conclusion

This review focused on the clinical outcomes of dental implants placed in patients with OLP. The survival rate in patients with OLP has been reported to be similar to that in the control group with healthy mucosal conditions. Implant treatment in patients with OLP is not contraindicated; however, the uncontrolled and active state of OLP may harm clinical outcomes. Reliable guidelines and protocols to control OLP in implant treatment have yet to be established owing to the limited number of studies. Further clinical information on implants in patients with OLP, with longer follow-up periods and a case-control group, is needed.