Oral Lichen Planus (OLP) is chronic muco-cutaneous inflammatory disorder of unknown cause. (1) There are various predisposing factors that are related to pathogenicity of OLP, most frequently involves bilateral buccal mucosa. It affects 0.1-4% of total population. (2, 3) Predominantly affecting females. OLP clinically can be characterized as reticular, atrophic, bullous and erosive/ulcerative type. (4) Symptoms of each type of Lichen Planus vary. (4)

Oral function is disturbed because of pain and other symptoms like burning sensation, soreness and sensitivity. Various treatment modalities have been evaluated, which include topical or intra-lesional steroids that has proven efficient for symptomatic OLP. But complete resolution from disease is not possible. (4) Steroids are used as immunosuppressive and anti-inflammatory agents. (5) Mechanism of action of Triamcinolone is by stimulation of Lipocortin- 1, L-10 and nuclear factor Kappa B. It suppresses antigen driven T-cells proliferation by inhibiting release of IL-l and monocytes. (6)

But with above treatment recurrence is common and long-term use of corticosteroid can cause various side effects. Nowadays Hyaluronic acid is commonly used because of its accelerated healing property and better results for longer duration. (7) Hyaluronic acid is naturally found in human body as extracellular matrix protein and in bovine vitreous humor. Hyaluronic acid plays an important role in regulating hemostasis. It also acts as bacteriostatic, anti-edematous, anti-inflammatory and fungistatic. Due to its high viscoelasticity, it reduces impingement of bacteria and virus in tissue. (8, 9)

One study found that mean pain score was 3.2G±0.79 with Triamcinolone alone while 2.4±0.52 with Hyaluronic acid after one month (p-value<0.05) (6). Another study found that the mean pain score was 0.33+0.83 with Triamcinolone while 0.56+.22 with Triamcinolone alone after two weeks (p>0.05). But lesion disappeared in 37% vs. 18.5% (p-value<0.05) respectively. (10)

The aim of this study to compare outcome of intralesional injection of Hyaluronic acid plus Triamcinolone versus Triamcinolone alone in the management of Oral Lichen Planus. Literature showed that combination of Hyaluronic acid plus Triamcinolone is more effective than Triamcinolone alone. But scarce work has been done before in this regard and no trial has been conducted before locally which would help us to implement use of combination injection instead of less effective treatment. Therefore, we have planned this study to find the            evidence for local population and implement findings of this study in local settings, as both drugs are available in local market. This will help us to improve our practice and outcome of treatment.

This Randomized Controlled Trial was conducted in Oral & Maxillofacial Surgery department, Punjab Dental Hospital (PDH), Lahore.  By using WHO calculator, sample size of 30 cases; (split mouth technique 30+ 30 side) group is calculated with 95% confidence level. 90% power of study and mean pain score 3.20±0.79 with Triamcinolone alone and 2.4 ±0.52 with Hyaluronic acid plus Triamcinolone.6   The study included patients ages 20-70 years of both genders with histopathologically confirmed Oral Lichen Planus, measuring 0.5-4cm. Exclusion criteria were the presence of dysplasia on histopathological analysis, history of chemotherapy and radiotherapy, pregnant or lactating females and a history of allergy to Hyaluronic acid.

After the approval of synopsis from ethical review committee, for this study 30 patients with biopsy proven OLP fulfilling the inclusion criteria was selected from OPD of Punjab Dental Hospital through consecutive sampling method. Informed consent was taken from the patient. All demographic details were collected and recorded on structured Proforma. All the procedure were done by a consultant having atleast 4 years of experience in Oral and Maxillofacial surgery. The procedure was carried in aseptic condition. Split mouth technique was used in this study. Using coin method one side (heads intervention on right control on left, tails intervention on left and control on right). Clinical appearance of lesion was noted. Size of the lesion was determined using divider and measured with scale in cm² on both sides. Severity of Pain was assessed using Visual Analogue Scale. Local anesthesia was injected on both side after disinfecting protocol. On control side intralesional injection of 40 mg/ml of Triamcinolone was given. On experimental side combination of 0.7ml of HA in one vial of 40mg/ml a Triamcinolone

was made after mixing well 1.7 ml of medication was injected in the Lesion. Insulin syringe was used for injecting both drugs. Then all the patients were followed-up in OPD for changes in size in cm² and pain by using Visual Analogue Scale in the lesion after 2 and 12 weeks.

Statistical Analysis:

The data was entered and analyzed using. SPSS version 20.0. Quantitative data were presented as mean and SD, while qualitative data were shown as frequency and percentages. The mean pain scores between groups were compared using an independent sample t-test and lesion disappearance was compared using a Chi-square test, with a significance level of P<0.05. 

Total 30 patients were included. The mean age of the patients was 48.76±14.67 year. There were 21(70.0%) male and 9(30)5 female. The mean duration of symptoms was 2.88±1.00 months. Among the patients, 13(43.0%) used Pan/Gutka and 18(60.0%) were smokers. Oral health assessment revealed that 9(30%) patients had good oral hygiene, 15(50%) had average hygiene and 6(20%) patients had poor oral hygiene.

At baseline and 2nd week mean pain score in Intervention group was 5.7±1.08, 1.60 ±0.62   and in control patients was 5.6±1.03 and 2.10±0.99. Table: 1 Disappearance of lesion showed no significant difference between groups. Although in intervention group rate of disappearance of lesion was higher. i.e. Intervention: 73.3% vs. Control: 50%, p-value=0.063. Fig: 1

At the 2nd week, no significant difference was observed between groups in different age categories, gender though patients in the intervention group had lower pain scores compared to the control group. Patients with both short and long symptom durations experienced lower pain scores in the intervention group, with longer-duration patients showing statistical significance. Oral health and smoking status had no significant impact on mean pain scores, though the intervention group consistently showed lower scores. Table: 2

Gender did not affect lesion disappearance rates, but the intervention group had a higher rate of disappearance. Age had no significant impact on disappearance of lesion between intervention and control group. However, patients had higher lesion disappearance rate as that of control group. Except patients with average oral health hygiene patients with good and poor oral hygiene had no significant impact on disappearance of lesion between groups. However, patients with average oral hygiene had significantly higher pain score in control group as compared to intervention group. Table: 3

Table:1 Pain at Baseline in study groups

Figure: 1

Table: 2 Pain at 2nd Week with intervention and Control group

Table: 3 Disappearance of lesion with intervention and control group

The management of OLP is very difficult due to its chronic nature that requires a long- term treatment. Corticosteroids are the first choice of drug for OLP. However, to date, no treatment for OLP is completely curative, and most available treatment modalities have focused on eliminating the signs and symptoms of the disease. (10)

However, due to adverse side effects such as glucose intolerance, hypertension, pancreatitis, osteoporosis, adrenal insufficiency, and interferences with pregnancy and nursing as well as gastrointestinal (GI), neurological, and psychological disorders, an adjunct modality to minimize these side effects and improve their efficacy can be highly favorable for patients. (11) Previous studies have reported that the intralesional injection of triamcinolone has fewer adverse effects than triamcinolone mouth rinse and that successful results have been achieved with injectable Triamcinolone. (12) Hyaluronan, as an important component of the extracellular matrix of vertebrates, plays an important role in many biological processes such as cell signaling, morphogenesis, matrix organization, tissue hydration, lubrication, wound healing, regulation of gene expression, and cell proliferation (13, 14). Studies on the therapeutic efficacy of Hyaluronic acid in the treatment of OLP are limited.

In this study we compared outcome of intralesional injection of Hyaluronic acid plus Triamcinolone versus Triamcinolone alone in the management of oral lichen planus.

Results showed that at 2nd week mean pain score was significantly lower in Intervention Group as that of control group. i.e. Intervention: 1.60 vs. Control: 2.10, (p-0.023). Disappearance of lesion showed no significant difference between groups. Although in intervention group rate of disappearance of lesion was higher. i.e. Intervention: 73.3% vs. Control: 50%, p-value=0.063.

Consistent with the findings of this study F Agha-Hosseini in his study reported that pain scores did not differ between the two groups when assessed after 2 weeks. The group treated with a combination of HA and Triamcinolone experienced a significantly better resolution of lesions and symptoms. Lesion disappearance in the intervention group after 3 months was seen in 48.1% patients and in control group lesion was disappeared in 44.4% patients. (10) However, in this study significant difference was seen for pain score at 2nd week with combination treatment as well as rate of lesion disappearance was higher as that of reported by F Agha-Hosseini. i.e. Intervention Group: 73.3% & Control Group: 50%. F. Agha Hosseini in his technical reported showed that combination of Triamcinolone/Hyaluronic acid mixture is potentially beneficial in the treatment of OLP. This finding supports the results of this study. (15)

Ahmed S. Hashem in his study compared topical HA with TA for treting oral lichen planus. Results showed that both TA and HA were found to reduce the VAS score, the degree of erythema, and size of the lesions after treatment. The application of HA is suggested, and is an effective substitute for TA in the treatment of OLP. (16)

An intra-lesional steroid has been proposed as an effective and simple method with the aim of attaining sufficiently high drug concentrations locally for an enhanced immunosuppressing effect but less systemic toxicity. (17) The TA aqueous injectable suspension remains longer at the injection site because it is insoluble. (18) Intra-lesional injection of TA has been known as a successful treatment of oral submucous fibrosis, temporomandibular joint osteoarthrosis, central giant cell granuloma, and cheilitis granulomatosa. (19, 20)

However, there have been few reports about the intralesional injection of TA in the management of OLP. Xia et al reported that the intralesional injection of TA reduced the signs and symptoms in 84.4% of patients with ulcerative OLP. (21) Xiong et al reported that the intralesional injection of TA that was used as a positive control showed improvement in 88.0% of patients. (22)

It has been shown that intralesional injection of Triamcinolone is safe and effective for decreasing the signs and symptoms of OLP. Triamcinolone is a synthetic corticosteroid, and injectable Triamcinolone material remains longer in the lesion because of its insolubility. (23, 24) The successful application of HA for inflammatory processes has been documented in rheumatology, orthopedics, and ophthalmology. (25) One possible mechanism for the longer lasting effect of treatment with HA combined with Triamcinolone may be the slow-release potential of Triamcinolone in this formulation, because the combination of Triamcinolone and polymer is better preserved

The conclusion of the study is that intralesional injection of Hyaluronic acid plus Triamcinolone was more effective that Triamcinolone alone for treating Oral Lichen Planus in terms of pain reduction and lesion disappearance. The addition of Hyaluronic acid can enhance treatment efficacy and serve as an effective additive treatment modality.

Limitation of the study:

The limitation of this study is that it the short duration of follow up 2 and 12 weeks may not fully capture long-term outcomes and potential recurrences of lesion.

Hyaluronic acid should be used alongside Triamcinolone for improved management or Oral Lichen Planus. Larger multicenter trials with extended follow-up are necessary to validate these findings.

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