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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 24  |  Issue : 2  |  Page : 74-80

Intralesional corticosteroid injections for the treatment of oral lichen planus: A systematic review


Department of Oral Diagnostic Sciences, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia

Date of Submission10-Dec-2019
Date of Acceptance31-Jan-2020
Date of Web Publication10-Nov-2020

Correspondence Address:
Dr. Hani Mawardi
Faculty of Dentistry, King Abdulaziz University, Al Ehtifalat St, Jeddah 21589
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdds.jdds_76_19

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  Abstract 


Background: Oral lichen planus is a chronic, immune-mediated disease that can impact the oral cavity significantly. Treatment options include topical and systemic corticosteroid therapy based on the disease severity. Intra-lesional corticosteroid injections (ILCI) have been incorporated in clinical practice as an effective modality to deliver treatment locally to expedite the healing process while limiting systemic toxicity. Purpose: The objective of this systematic review was to evaluate the role of ILCI in treating OLP. Methods: A systematic review of the literature was conducted in the PubMed and Web of Science databases following PRISMA protocol and up to September 2019. All English-language literature on ILCI for OLP was included. Relevant articles were systematically reviewed using multiple levels of elimination by title, abstract, and full text. Data from the included studies were extracted and analyzed. A total of six studies met the inclusion criteria. Results: Triamcinolone acetonide intra-lesional injection demonstrated efficacy and rapid healing of OLP lesions in three studies. Minor adverse events of secondary oral candidiasis and cushingoid features were reported. Conclusion: ILCI may be considered as an effective treatment option for OLP lesions with minimal side effects and risk of disease relapse.

Keywords: Corticosteroids, intra-lesional, lichen planus, oral


How to cite this article:
Alsubhi A, Salem N, Mohab M, Alghamdi B, Alghamdi N, Alasiri RA, Sindi RA, Almastadi RA, Alfayez NM, Alsulaimani M, Alsheikh W, Alhamed S, Mawardi H. Intralesional corticosteroid injections for the treatment of oral lichen planus: A systematic review. J Dermatol Dermatol Surg 2020;24:74-80

How to cite this URL:
Alsubhi A, Salem N, Mohab M, Alghamdi B, Alghamdi N, Alasiri RA, Sindi RA, Almastadi RA, Alfayez NM, Alsulaimani M, Alsheikh W, Alhamed S, Mawardi H. Intralesional corticosteroid injections for the treatment of oral lichen planus: A systematic review. J Dermatol Dermatol Surg [serial online] 2020 [cited 2020 Nov 25];24:74-80. Available from: https://www.jddsjournal.org/text.asp?2020/24/2/74/300398




  Introduction Top


Lichen planus (LP) is a common, chronic inflammatory disease of the oral mucosa, most frequently affecting the buccal mucosa, gingiva, and tongue symmetrically, in addition to the skin and genital mucosa.[1] Oral LP (OLP) affects 0.1%–4% of the general population. It is 1.5–3 times more frequent in females and common in the middle-aged and elderly population.[2],[3] Clinically, OLP presents as reticular/hyperkeratotic, erythematous/erosive, and/or ulcerative changes in the oral cavity and rarely as papular or bullous lesions. The most common form is reticular/hyperkeratotic, which is characterized by Wickham's striae and often asymptomatic.[4] Erythematous/erosive and ulcerative forms may overlap and tend to be more symptomatic, which encourage patients to seek treatment.[2],[3],[5]

In general, treatment options for OLP are tailored toward the patient's symptoms and are based on the disease activity and severity including corticosteroids and other immunosuppressive and biologic agents in topical or systemic formulations.[6] The first-line treatment for mild-to-moderate disease is topical corticosteroids, including gels, sprays, and solutions/elixirs. Other treatment options in a topical formulation reported in the literature include tacrolimus and cyclosporine. For more severe cases, systemic immunosuppressive therapy including corticosteroids can be used alone or combined with topical treatment in addition to hydroxychloroquine or azathioprine.[7] Patients with localized (1–3 sites) yet severe lesions may benefit from topical therapy, which can be slow acting. In addition, systemic corticosteroids may be an overtreatment considering the number of lesions and may not provide the needed relief in a timely manner. For such cases, intralesional injection is a viable treatment option with the advantage of delivering a higher concentration of corticosteroid locally with less risk of systematic toxicity.[8] So far, the exact benefit of intralesional corticosteroid therapy as a monotherapy or in combination with topical or systemic corticosteroids is not well understood.[9]

The primary objective of this systematic review was to determine the role of intralesional corticosteroid injections in the treatment of OLP lesions. The secondary objective was to evaluate the relative risks with respect to adverse events associated with intralesional corticosteroid injections whether locally or systemically.


  Methods Top


No ethical approval was indicated considering the systematic review nature of this study. A systematic search of the literature was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis protocol, using population, intervention, control and outcome (PICO) questions and MeSH words via the PubMed and Web of Science search engines up to September 2019. The inclusion criteria were as follows: (1) language – English; (2) clinically and histopathologically confirmed ulcerative and/or erosive OLP; and (3) articles with a focus on intralesional corticosteroid injection as an intervention for OLP only. The exclusion criteria were non-English articles, studies of other steroid delivery systems, or studies with a focus on diseases other than OLP. Relevant articles were systematically reviewed by five reviewers using different levels of elimination, including the title, abstract, and full-text analysis [Figure 1]. The extracted data from eligible studies for the final review and analysis included study design, number of participants, type of steroid used, control subjects, assessment tools, study outcome, adverse events, and time to relapse.
Figure 1: Process of articles elimination

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  Results Top


The literature search using PubMed and Web of Science yielded a total of 49 studies, seven of which met the inclusion criteria (published from 1967 to 2018). Four of six studies were randomized controlled trials, including one split-mouth study design. In addition, there was one quasi-experimental study and two case series. None of all included studies have indicated if intralesional corticosteroid injections were administered as the first-line treatment; however, five studies have excluded patients who are currently or have used other topical or systemic corticosteroid therapy within a range of 1 to 12 weeks prior to the enrollment [Table 1].[8],[9],[10],[11],[12]
Table 1: The measurable outcomes of the included studies

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Lee et al. conducted a randomized controlled trial comparing triamcinolone acetate (TA) intralesional injections and TA mouthrinse in patients with OLP.[10] Both the interventions resulted in a reduction of pain and burning sensations in the mouth as measured using the Visual Analog Scale (VAS) and Oral Health Impact Profile-14 questionnaire. In the same study, Escudier et al. scoring was used to measure the ulcer size in both the groups, and an equal decrease in OLP lesion size was reported over 6 weeks following the treatment.[13] Overall, the rate of adverse events reported was significantly higher in the TA mouthrinse group and included secondary oral candidiasis in eight patients (TA mouthrinse group); only one patient developed Cushingoid features, which resolved after 2 weeks (TA intralesional injection group). The groups did not show a significant difference in relapse time after a 1-year follow-up.[10]

Liu et al. published a randomized clinical trial comparing TA intralesional injections with compounded betamethasone intralesional injection delivered to patients diagnosed with erosive OLP.[8] Compounded betamethasone injections resulted in a greater reduction of OLP lesion size (mean reduction of 10 mm) than TA injections. Furthermore, betamethasone injections showed a greater reduction in ulcer size (measured using a periodontal probe) than TA injections (93.1% vs. 66.7%). Both the agents demonstrated similar levels of pain reduction (numeric rating scale of 3.414 ± 2.027 for the betamethasone injection group and 3.0 ± 2.133 for the TA injection group) at the end of the treatment period (total of 14 ± days).[14] However, the reported recurrence rate was 14.8% for the betamethasone group and 45% for the TA injection group. Adverse events were reported in only one patient, who received betamethasone injection and developed a slight burning sensation in the throat area 6 h postinjection that resolved spontaneously without treatment. No other adverse events were reported.[8]

Xiong et al. conducted a randomized clinical trial on patients with erosive OLP as well.[12] In this study, the efficacy of TA intralesional injections versus Bacillus Calmette–Guérin polysaccharide nucleic acid (BCG-PSN) injections was evaluated. BCG-PSN injections were reported to be as effective as TA injections in improving the VAS score and size of erosive lesions as measured by periodontal probe, suggesting its use as an alternative agent to treat OLP sites. Both the agents resulted in minor side effects in two patients (out of 25; 8.0%), who developed tingling and burning sensations at the site of injection in the TA group, while three patients (out of 31; 9.7%) in the BCG-PSN group developed swelling and a burning sensation at the injection site. In terms of the recurrence rate, no significant difference was noted between the two agents in a 3-month follow-up period.[12]

Kuo et al. conducted a quasi-experimental study with a new treatment protocol for erosive OLP consisting of TA intralesional injections in addition to oral prednisolone.[15] In this study, 90% of OLP ulcerations were healed in 2–3 weeks. The risk of recurrence was reported to take place between 3 and 24 months, even for patients who had 12 months of complete remission. However, recurring lesions continued to be responsive to the same treatment protocol. No side effects associated with this protocol were reported.[15]

Xia et al. conducted a split-mouth, randomized clinical trial to evaluate the efficacy of TA injections.[11] In this study, OLP sites received TA injections, while the healthy side of the oral cavity was considered as a control group. Two weeks following the first TA intralesional injection, there was a statistically significant reduction in pain VAS score (85.0%) in addition to erythema and ulceration (78.0%). Twenty-three patients (51.1%) demonstrated more than 80% reduction in ulcerative area size, while 22 patients (48.9%) needed a second round of TA intralesional injections. Four weeks following the first TA injection, 40 patients (88.9%) displayed a complete resolution of erythematous sites. At the same time, 38 patients (84.4%) displayed a complete resolution of ulcerations and 7 patients (15.6%) demonstrated <81.0% reduction in ulcerative areas after receiving two TA injections. No adverse reactions were reported in this study.[11]

Two case series were included in this study. Sleeper et al. reported an OLP case series of seven patients treated successfully using TA injections.[16] Three of seven patients reported a dramatic relief of associated signs and symptoms, with complete healing of the ulcerative areas within 72 h. The remaining four patients had partial healing, which was asymptomatic. No significant adverse events were reported in this case series except for a mild discomfort associated with the TA injection for all seven patients. Lee et al. reported a series of 62 OLP patients who received TA injections once a week for 4–6 weeks.[9] Fifty patients (80.6%) showed an improvement in symptoms, in which 29 of them (58%) had recurrent disease. Patients were evaluated using the VAS and Oral Health Impact Profile-14 questionnaire.


  Discussion Top


OLP is an immune-mediated condition often imposing on a patient's quality of life.[17] In general, asymptomatic OLP requires no medical intervention other than patient education and long-term follow-up. However, patients with the active and symptomatic disease require further intervention from medical and dental professionals. Available treatment options vary and range between topical corticosteroid and calcineurin inhibitors to systemic immunosuppressive therapy; each has its advantages and potential toxicities. Patients with localized yet severe and painful ulcerations require immediate intervention to relieve symptoms. In such cases, systemic corticosteroids would provide a fast and effective response. However, the associated contraindications and side effects can be often challenging, especially for medically complex patients. Intralesional corticosteroid injections have the advantage of delivering a high concentration of the active agent locally, increasing its efficacy and producing minimal to no systematic toxicity. Furthermore, due to its insolubility, it can remain longer in the tissues, thus maintaining its efficacy.[10]

Considering the wide use of intralesional corticosteroid injections, physicians, and dentists, this systematic review aimed to assess their efficacy in reducing OLP signs and symptoms, evaluate the rate and time of relapse following administration of intralesional injections, and examine their possible side effects. A total of seven articles were eligible and included in this systematic review. There were four randomized controlled trials, including one split-mouth design, as well as one quasi-experimental study and two case series. In terms of pain level and signs of OLP (lesion size, erythema, and ulceration) assessment, four studies supported the benefit of corticosteroid intralesional injection for OLP (one randomized controlled trial [RCT], one quasi-experimental study, and two case series) in reducing pain level and decreasing lesion size, ulcerations, and erythema.[11],[15],[16] The time to response varied and ranged between 72 h and 2 weeks. The overall response rate was between 45% and 90%. A single study reported that a combination of systemic and intralesional corticosteroids accelerated and promoted healing for OLP cases, which was effective in reducing patients' symptoms.[15] In addition to corticosteroid intralesional injection, other therapeutic agents (i.e., TA mouthwash and BCG-PSN injections) have demonstrated some benefit and should be considered for OLP cases. On the other hand, an RCT study reported no significant difference in reducing pain and lesion size, erythema, or ulceration between corticosteroid rinses and intralesional injections.[10]

The application of intralesional corticosteroid injections is considered safe, as reported adverse effects were limited and minor. They ranged from tingling and burning sensations to Cushingoid features, which were reported in a single case and was self-limiting. Due to its mechanism of action, secondary oral candidiasis with corticosteroid use should always be considered; this was reported with a corticosteroid mouthrinse.[10]

Based on the data extracted from all seven studies, risk and time to relapse with intralesional corticosteroid injections are insignificant. The overall rate of relapse ranged from 14.8% to 58% within a mean period of 2.41 ± 0.92 months to 12 ± months. In the study by Liu et al., the relapse rate was significantly higher with TA intralesional injections than betamethasone intralesional injections, with a relapse rate of 45% and 14.8%, respectively.[8] Furthermore, a single study comparing TA injection with BCG-PSN injection concluded that there were no significant differences between the two agents regarding the reoccurrence rate and relapse interval.[12] However, there was a trend for faster relapse in the TA intralesional injection group that was observed for 12 weeks.

The current study has several limitations. First, the total number and quality of studies included were limited. In addition, the sample size varied, with the lowest being seven patients.[16] However, four of six studies were RCT studies. Second, the assessment methods and scoring of the study subjects were not standardized and were even lacking in four studies. Escudier et al. scoring was used only in a single study that evaluated three main parameters – site involvement, severity (keratosis, erythema, and ulceration), and pain level – and considered a dynamic and sensitive scoring system for disease activity.[10],[13] The reticular, erosive, and ulcerative (REU) scoring system for OLP was first introduced by Piboonniyom et al and implemented in a single study as well. Overall, it is a simple scoring system that relies on objective parameters to measure disease activity.[2],[11] In addition, different methods of assessment were used among these studies, including measurement of OLP lesions using a periodontal probe and dividing the lesions into special categories according to the clinician's clinical examination, which makes it harder to compare outcomes. Finally, the follow-up duration of the included studies was variable and relatively short, ranging between 2 and 24 weeks.[2],[14],[18]


  Conclusion Top


The outcome of this systematic review supports the application of intralesional corticosteroid injections in the management of OLP with the risk of relapse based on a case-by-case evaluation. The associated adverse reactions reported were minor and included secondary candidiasis, Cushingoid features, a burning sensation, oral swelling, and a tingling sensation. More randomized prospective clinical studies are needed to confirm this result.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Piboonniyom SO, Treister N, Pitiphat W, Woo SB. Scoring system for monitoring oral lichenoid lesions: A preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:696-703.  Back to cited text no. 2
    
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Liu C, Xie B, Yang Y, Lin D, Wang C, Lin M, et al. Efficacy of intralesional betamethasone for erosive oral lichen planus and evaluation of recurrence: A randomized, controlled trial. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;116:584-90.  Back to cited text no. 8
    
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Lee YC, Lee JS, Jung AR, Park JM, Eun YG. Factors affecting the result of intralesional corticosteroid injection in patients with oral lichen planus. Clin Exp Otorhinolaryngol 2018;11:205-9.  Back to cited text no. 9
    
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Lee YC, Shin SY, Kim SW, Eun YG. Intralesional injection versus mouth rinse of triamcinolone acetonide in oral lichen planus: A randomized controlled study. Otolaryngol Head Neck Surg 2013;148:443-9.  Back to cited text no. 10
    
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Xia J, Li C, Hong Y, Yang L, Huang Y, Cheng B. Short-term clinical evaluation of intralesional triamcinolone acetonide injection for ulcerative oral lichen planus. J Oral Pathol Med 2006;35:327-31.  Back to cited text no. 11
    
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Xiong C, Li Q, Lin M, Li X, Meng W, Wu Y, et al. The efficacy of topical intralesional BCG-PSN injection in the treatment of erosive oral lichen planus: A randomized controlled trial. J Oral Pathol Med 2009;38:551-8.  Back to cited text no. 12
    
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Escudier M, Ahmed N, Shirlaw P, Setterfield J, Tappuni A, Black MM, et al. A scoring system for mucosal disease severity with special reference to oral lichen planus. Br J Dermatol 2007;157:765-70.  Back to cited text no. 13
    
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Farrar JT, Troxel AB, Stott C, Duncombe P, Jensen MP. Validity, reliability, and clinical importance of change in a 0-10 numeric rating scale measure of spasticity: A post hoc analysis of a randomized, double-blind, placebo-controlled trial. Clin Ther 2008;30:974-85.  Back to cited text no. 14
    
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Kuo RC, Lin HP, Sun A, Wang YP. Prompt healing of erosive oral lichen planus lesion after combined corticosteroid treatment with locally injected triamcinolone acetonide plus oral prednisolone. J Formos Med Assoc 2013;112:216-20.  Back to cited text no. 15
    
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Sleeper HR. Intralesional and sublesional injection of triamcinolone acetonide for oral lichen planus. Yale J Biol Med 1967;40:164-5.  Back to cited text no. 16
    
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Cheng YS, Gould A, Kurago Z, Fantasia J, Muller S. Diagnosis of oral lichen planus: A position paper of the American Academy of oral and maxillofacial pathology. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122:332-54.  Back to cited text no. 17
    
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Slade GD. Derivation and validation of a short-form oral health impact profile. Community Dent Oral Epidemiol 1997;25:284-90.  Back to cited text no. 18
    


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