Background
Oral Lichen Planus (OLP) is among the most prevalent dermatologic diseases that occurs within the oral cavity, affecting approximately 0.5% to 2% of the global population [
1]. It is characterized by white reticular or erosive lesions on the oral mucosa, which can cause pain, discomfort and impaired daily activities for many patients [
2,
3]. The condition mainly affects women over the age of 40 with a 2:1 female-to-male ratio. Although several therapeutic options are available for managing OLP, including corticosteroids and calcineurin inhibitors, photochemical therapy, and retinoids; topical corticosteroids are commonly used as the primary pharmacological remedy, and intralesional corticosteroids are also effective in managing OLP by enabling high drug concentrations at the injected site [
4,
5].While numerous treatments are accessible for the disease, they usually cause side effects and do not ensure a permanent cure. For example, extended use of intralesional corticosteroids has been linked to several systemic adverse effects, including taste loss, mouth dryness, candidal infection, mucosal atrophy and so on.
Platelet concentrates (PCs) are autogenous substances obtained from blood, which contain supraphysiological levels of platelets and growth factors(GFs). Autologous biological product derived from the patient's blood, are widely used in regenerative medicine due to their autogenous sources of GFs that can induce tissue repair and regeneration, while avoiding any potential immunological or allergic reactions [
6]. PCs are obtained through blood centrifugation, resulting in the concentration of GFs and cytokines that exert a beneficial effect on inflammation, angiogenesis, stem cell migration and proliferation, which in turn enhancing the potential for repair and regeneration [
7,
8]. Platelet-rich plasma (PRP), plasma rich in growth factors, Injectable-platelet-rich fibrin (i-PRF), and concentrated growth factors are examples of such products, classified according to their preparation protocols [
9].In recent research, Dohle et al. demonstrated that PRF has a positive impact on wound healing and angiogenesis, while Fujioka-Kobayashi showed that dense granules within platelets release mediators like histamine, serotonin, and dopamine that aid in pain reduction when included in platelet concentrates [
10,
11]. The efficacy of platelet concentrates in treating OLP patients by reducing the immune response and alleviating symptoms has been supported by several clinical trials [
12‐
15].
As PCs products with fewer or no side effects become increasingly popular, it is crucial to compare their clinical performance with that of topical corticosteroids, especially since the most significant expectation among OLP patients from their medications is rapid pain relief [
16]. Therefore, this is the first research evaluates the effectiveness of blood-derived products compared to steroid therapy for OLP treatment. By providing evidence-based recommendations, this meta-analysis supports clinicians in choosing suitable therapies, particularly in cases where systemic diseases prohibit the use of steroids or to avoid their side effects.
Methods
The protocol was also registered in advance with the PROSPERO database (CRD42023415372).
Database and search strategy
The studies included were met the following inclusion criteria (without language restriction):
-
P (population): Adult patients who were clinically and/or histologically diagnosed as OLP accordance to WHO criteria without history of corticosteroid therapy in topical lesion (in the oral cavity) in the past 2 weeks or systemic delivery in the past 4 weeks.
-
I(Intervention): Patients were treated with injections of PC derivatives, such as PRP and i-PRF, throughout the course of treatment [
17].
-
C (Comparison): The interventions in this study comprised receiving corticosteroid injection therapy over the course of treatment. The outcome measures for this study comprised pain relief, assessed through changes in the 0–10 scale, using visual analog scale (VAS) or numerical rating scale (NRS). Clinical resolution by Thongprasom (Sign score) was also evaluated using experimental and control procedures. Lesion severity on each site was scored based on Reticulation/keratosis, erythema, and ulceration (REU) score and lesion size, while reported side effects were also recorded.
-
S (study): Controlled trials, randomized controlled trials, randomized cross-over design trials and cohort studies.
A comprehensive search was performed in databases, including Embase, Cochrane Central Register of Controlled Trials, PubMed, OVID Medline, and WanFang, were searched from their inception up to April 2023 (see the appendix in the electronic Supplementary Table S
1). Two reviewers (YM and CH) assessed all titles and abstracts, and literature management was conducted using Endnote. Potentially eligible abstracts and abstracts with disagreement or insufficient information were evaluated in full-text screening.
Two reviewers (CH and JF) independently extracted data from relevant research papers. The collected information comprised authors, country, year of publication, study design, number of subjects, haracteristics of the study population such as age and gender, experiment and control groups, evaluation methods, adverse reactions, and main study findings. In case of any discrepancies, they were resolved through discussion and consensus. Whenever required, the authors were contacted for additional data.
Quality assessment
The methodological quality of RCTs included in our research will undergo independent evaluation by two reviewers(YM and WW). In cases of disagreement, they will resolve by a third reviewer's judgment. To assess the quality of the involved citations, we use the Cochrane ROB tool [
18]. The following items will be evaluated: (1) Randomization process, (2) Deviations from intended interventions, (3) Missing outcome data, (4) Measurement of the outcome, (5) Selection of the reported result, (6) Overall.
Statistical analysis
The WMD for VAS or NRS scores, as well as the MD for sign scores and REU were analyzed for both experiment and control procedures after therapy. Descriptive and statistical analyses were conducted, with an evaluation of heterogeneity through Q statistic and inconsistency index (I2) statistic. The fixed-effects model was used when heterogeneity was present (I2 > 50%), while a random-effects model was utilized for data without significant heterogeneity (I2 < 50%). Subgroup analysis was performed by different blood derivative components. A sensitivity analysis was performed, sequentially eliminating each study to verify the stability of results. All analyses were conducted using To evaluate potential publication bias, both Beggs' and Eggers' tests were carried out with a statistical significance level set at α = 0.05.All statistical analyses were performed using STATA software (version 15.1, Stata/SE).
Discussion
Oral lichen planus is an autoimmune, chronic inflammatory disorder which is identified by the basal layer of the oral epithelium with T-cell mediation [
25]. While its exact cause remains unknown, growing evidence suggests that immune dysregulation significantly contributes to its development through multiple mechanisms. Platelets serve as potential sources releasing anti-inflammatory cytokines and regulating inflammatory mediators [
26]. PCs contain a diverse array of GFs, including vascular endothelial growth factor, insulin-like growth factor-1, basih factor β-1 and platelet-derived growth factor-BB, which are released upon activation [
27]. These GFs stimulate mesenchymal cell recruitment, regulate keratinocyte and regulatory T-cell functions, inhibit inflammatory cytokine and transcription factor expression, and reverse extracellular matrix destruction in OLP lesions [
28]. PRP and i-PRF contain TGF-β, PDGF, EGF, VEGF, IGF [
29], and fibronectin, boost cell proliferation, facilitate angiogenesis, and promote wound healing-related cell migration, all of which aid in tissue regeneration [
30,
31]. Additionally, PRP and i-PRF release GFs and cytokines that significantly regenerate tissues through their angiogenesis properties [
32]. The 3D fibrin matrix containing autologous plasma extract carries cytokines and GFs, both of which play vital roles in the regeneration process. Huber et al. found that PRP promotes anti-inflammatory cytokines production, which interact with soluble receptors and inhibitors to regulate inflammation and growth factor activity [
33,
34]. Additionally, i-PRF actively augments proliferation and migration of endothelial cell and fibroblast, promoting tissue regeneration and wound healing by stimulating cell migration and proliferation during the proliferation phase [
11].
This article summarizes the results of eight studies that assessed the efficacy of autologous blood derivatives, including PRP and i-PRF, as well as corticosteroid injections for managing OLP. Both blood derivatives and corticosteroids were found to be effective in relief pain and clinical scores in OLP patients. However, some discrepancies exist in earlier therapeutic responses. The Elghareeb [
19] study reported a higher frequency of side effects, particularly pain, with PRP treatment compared to steroids. Conversely, the Al-Hallak study [
15] showed a significant decrease in pain scores for both treatment groups, while the Ahuja study [
23] revealed that PRP provided comparable or better comparative results than topical steroids in later phases of treatment, in spite of initially showed slightly less reduction in assessed parameters. Notably, PRP exhibited slightly less reduction in symptoms comparing with i-PRF during the first two weeks of treatment [
35]. It appears that i-PRF may have a faster clinical response than PRP in managing OLP. Furthermore, the Hijazi study [
20] suggested that although PRP had a slower clinical response than TA injections, both treatments exhibited similar complete remission rates, with no significant differences observed in pain score, Sign score, or lesion area remission. The observed differences could be attributed to variations in the duration of release and peak time of GFs reported across studies [
36,
37].The UE Shinnawi study [
38] also supports this notion, showing a clear improvement in symptoms with blood derivatives after the first two weeks of treatment. Several other studies have assessed the efficacy of injection PCs in managing refractory erosive OLP patients who showed no response to corticosteroid treatment [
39]. The results revealed that PCs therapy is an effective approach for treating atrophic-erosive lesions associated with this condition, which is generally unresponsive to corticosteroids. In a study by Samiee et al. [
40], involved ten female patients, and found that PCs treatment resulted in complete symptom absence within an average of 13 months after the procedure. Similarly, another study by Anitua et al. [
41], which included four female participants, reported significant relief in pain scores and complete healing following one or two PCs infiltrations. Additionally, Piñas's study [
13] study with fifteen participants demonstrated PCs therapy's ability to significantly reduce pain scores with a mean follow-up duration during which participants remained symptom-free of 47.16 months. Our findings provide substantial evidence of platelets derivates therapy's effectiveness as a treatment option for refractory erosive OLP.
Overall, no statistically significant difference were found in recurrence rates or side effects in the literature included in the study, supporting the injection of automatic blood derivatives as PRP and i-PRF as safe and effective options in managing oral discomfort and lesions for patients who are unable to tolerate or do not respond well to traditional corticosteroid therapy. The findings from the Archana Shankar [
30] and Sameeulla Shaik [
42] studies provide further support for this conclusion by demonstrating no recurrence at one, three, and six-month follow-ups subsequent to the treatments administered. The study's results offer compelling evidence for the effectiveness of PRP and i-PRF in managing OLP, which presents a promising therapeutic option for individuals struggling with this condition. For patients who are unable to tolerate or do not respond well to traditional corticosteroid therapy, our findings may provide an alternative treatment approach.
When interpreting the findings of this review, several limitations need to be considered. Firstly, the included studies demonstrated moderate-to-severe heterogeneity that could be attributed to subjectivity in the measured indices. Based on the results of Begg's and Egger's tests, no significant of publication bias was detected in our meta-analysis. However, it is important to note that these tests do not guarantee the absence of publication bias, and other types of bias such as selective outcome reporting or language bias could still affect the results. Additionally, limited number of research included in the present meta-analysis may have reduced the power of these tests to detect publication bias. Due to the chronic nature and recurrence of OLP, short follow-up periods could lead to information bias and restrict the assessment of long-term clinical performance. Consequently, further research is required to determine the optimal dosage and frequency of Platelet concentrates injections for treating OLP and compare its long-term efficacy and potential adverse effects with those of other treatments [
42]. In addition, longer-term studies are needed to determine the durability of the treatments and their potential side effects. Moreover, compared to some topical drugs, patients require timely follow-ups and demonstrate adherence to certain medical protocols. Cost-effectiveness analysis is therefore critical, given that the high cost of ACPs might impede access to some patients. Despite these limitations, our study supports the notion that ACPs represents a potentially effective and safe treatment option for OLP, particularly for patients who face increased risks of complications from corticosteroid therapy [
43].
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