Oral lichen planus (OLP) is a chronic inflammatory disease that primarily affects the mucous membranes of the oral cavity [1-3]. The immune-mediated mechanism underlying OLP is characterized by a T-cell-mediated response against basal epithelial cells, leading to degeneration of the basal layer and subsequent mucosal damage [4,5]. Histopathological examination typically reveals a band-like infiltration of lymphocytes, predominantly T-cells, in the subepithelial region. This inflammatory infiltrate plays a crucial role in the clinical manifestations of OLP, which include reticular, erosive, and atrophic forms of mucosal lesions [6,7].

Treatment of OLP is primarily aimed at symptom management and the reduction of inflammation. Topical corticosteroids are the mainstay of treatment and are often effective in controlling symptoms in patients with mild to moderate disease. However, in more severe cases, or when topical treatments fail, systemic corticosteroids may be used. Unfortunately, long-term systemic steroid use is associated with a range of side effects, including weight gain, hypertension, hyperglycemia, and osteoporosis, which limits their utility in chronic conditions like OLP [8].

Intralesional steroid injections (ILIs) have emerged as a promising alternative for patients who do not respond to topical steroid treatments or have adverse effects on systemic treatments. Intralesional therapy delivers corticosteroids directly into the affected tissues, providing high local concentrations of the drug while minimizing systemic exposure. Several studies have demonstrated the efficacy of intralesional triamcinolone in reducing the size and severity of OLP lesions, as well as in alleviating pain and discomfort [1-3,9].

In this study, we investigate the long-term clinical outcomes of ILIs administered or managing OLP in patients resistant to both topical and systemic steroid treatments.

This study was approved by the Institutional Review Board of Yonsei University Dental Hospital (IRB no. 2-2024-0047; approval date: July 30, 2024). The requirement for written informed consent was waived by the committee because of the retrospective nature of the study.

1. Case 1

A 64-year-old female patient returned for evaluation at the Department of Orofacial Pain and Medicine, Yonsei University Dental Hospital, after a two-year absence from follow-up, presenting with pain localized to the bilateral buccal mucosa and gums, exacerbated by spicy foods. She described a burning sensation with a Numerical Rating Scale (NRS) score of 4, without spontaneous pain. Her medical history included unstable angina, managed with aspirin, carvedilol, and benidipine hydrochloride. A review of existing literature reveals no evidence linking these medications, including the beta-blocker carvedilol, to the exacerbation of OLP [10,11].

The patient had been diagnosed with OLP through an incisional biopsy 4 years prior and had received treatment at the Department for 2 years. During that time, her symptoms persisted despite treatment with topical and systemic corticosteroids. Notably, systemic corticosteroids caused adverse effects, including facial swelling, which limited their long-term use.

At the time of her return to the clinic, treatment was resumed with topical steroid therapy (Prednisolone-Ampicillin gargle and dexamethasone ointment) and supportive measures such as sodium lauryl sulfate (SLS)-free toothpaste. After 1 month, her condition had worsened significantly, with an NRS score of 8. Although she consistently used the Prednisolone-Ampicillin gargle, she had not adhered to the prescribed steroid ointment. Due to the lack of improvement, ILIs were introduced.

The ILI procedure involved antiseptic preparation with Betadine and sterile saline, followed by injections using a 29G syringe. Each lesion received 0.5 mL of triamcinolone acetonide, administered in doses of <0.1 mL spaced approximately 1 cm apart [9]. The injections were delivered bilaterally to the buccal mucosae. The patient was advised to continue topical steroid therapy regardless of her adherence.

Two months after restarting treatment, the patient reported a 40%-50% reduction in pain (NRS score of 5), prompting an additional injection to the left buccal mucosa to address residual discomfort. Three months after restarting, her symptoms had further improved, with an NRS score of 2 and no additional injections required by the fourth month. This sustained improvement suggested a potential slow-release effect of triamcinolone acetonide.

Five months after restarting treatment, an additional injection was administered to the right buccal mucosa due to minor discomfort. Over the course of treatment, the patient exhibited a pattern of minor exacerbations followed by gradual improvement. At the most recent follow-up, 1 year and 10 months after restarting treatment, the patient’s OLP was well-managed with an NRS score of 2. For the preceding 6 months, no further ILI had been required, and her condition was maintained with intermittent topical steroid therapy despite low compliance (Fig. 1).

2. Case 2

A 30-year-old female patient, without any specific systemic background diseases, returned to the Department of Orofacial Pain and Medicine, Yonsei University Dental Hospital, following a year-long lapse in treatment. She presented with severe burning pain throughout the oral cavity during meals, reporting an NRS score of 6 without spontaneous pain. The patient had first visited the clinic 5 years prior, during which an incisional biopsy confirmed the diagnosis of OLP. She received intermittent treatment for 4 years, but her symptoms fluctuated between exacerbation and remission, largely due to low compliance with topical steroid therapy attributed to her shift work schedule.

Systemic corticosteroids, although briefly effective, had previously induced severe side effects, including facial swelling, rashes, heat sensations, and tremors in the extremities, rendering long-term use unfeasible. Upon her return to the clinic, systemic steroids, specifically methylprednisolone starting at 16 mg and tapered by 4 mg weekly, were represcribed to control symptoms; however, side effects recurred, complicating further administration. This is similar to Case 1, where systemic corticosteroid use was also limited by adverse effects.

After 3 months without significant improvement following her return, ILI were initiated. Two injections were administered at 1-month intervals to the buccal mucosae, combined with topical steroid therapy. By 2 months after the initial ILI, significant improvement was observed, with an NRS score of 1 and visibly reduced lesions.

Following this improvement, minimal ILI was required, with the final injection administered approximately 1 year after her return to the clinic. At her most recent follow-up, 1 year and 5 months after her return, her symptoms remained well-managed despite low compliance with topical steroid therapy, and no further exacerbations were reported (Fig. 2).

These case reports demonstrate that ILI is a highly effective treatment modality for OLP, particularly in patients resistant to conventional therapies such as topical corticosteroids or systemic steroids. This approach has shown sustained effectiveness with minimal frequency of injections and without severe side effects, even in challenging clinical scenarios, such as patients unable to tolerate systemic steroids due to adverse effects or those with poor compliance with topical therapies.

In addition, ILI is particularly valuable for patients with diabetes or other conditions where systemic steroids may complicate blood glucose control, offering a safe and effective alternative. Its favorable response profile, as demonstrated in these cases, may also reduce the likelihood of follow-up loss during treatment. However, since a single injection may not yield optimal results, repeating the procedure two to three times can significantly enhance therapeutic outcomes [12].

The efficacy of ILIs in OLP likely arises from their ability to deliver high concentrations of corticosteroids directly to the affected tissues. Corticosteroids, such as triamcinolone acetonide, clobetasol propionate and fluocinonide, function by inhibiting the release of pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which play key roles in the pathogenesis of OLP [13]. By reducing the recruitment of inflammatory cells, particularly T-cells, intralesional steroids can help suppress the immune response that drives the chronic inflammation seen in OLP lesions [1,2]. Although conventional topical steroid therapies were prescribed concurrently, considering that the patients had not responded well and showed low compliance with these therapies, this localized approach is suggested to provide sufficient efficacy without the risk of systemic side effects, such as hyperglycemia, osteoporosis, and hypertension, which are common in long-term systemic steroid use [4].

Our outcomes are consistent with previous studies that have investigated the use of ILIs for OLP. For instance, Lee et al. [3] conducted a randomized controlled study comparing intralesional injections of triamcinolone acetonide with a mouth rinse containing the same corticosteroid. Similarly, Xia et al. [1] demonstrated the effectiveness of short-term intralesional triamcinolone injections in reducing the severity of ulcerative OLP, with marked improvement in clinical symptoms within a few weeks of treatment. These studies, along with our case reports, suggest that intralesional therapy offers a valuable alternative for patients who either cannot tolerate systemic steroids or fail to respond to topical treatments.

However, it is important to acknowledge that while intralesional injections are effective, they are not without potential risks. According to previous studies, common side effects may occur, such as localized pain, mucosal atrophy, and in rare cases, secondary infections [2,4]. Fortunately, both patients in our study tolerated the treatment well, with no significant adverse events, likely due to the minimal frequency of injections and the clinician’s following the protocols suggested in previous studies [9].

This treatment approach could be applied to other chronic inflammatory oral conditions, such as mucous membrane pemphigoid and erythema multiforme, which share pathophysiological similarities with OLP. Studies on pemphigus, for instance, have shown that intralesional steroid (triamcinolone acetonide) injections can disrupt the formation of tertiary lymphoid structures (TLSs), small aggregates of immune cells that perpetuate local inflammation in chronic diseases [12]. The breakdown of these structures by localized corticosteroid treatment can provide lasting symptom relief and represents a promising avenue for further research into OLP and related conditions.

There is also growing interest in exploring alternative or combination therapies, where ILIs may be paired with or replaced by other immunomodulatory agents, such as calcineurin inhibitors (e.g., tacrolimus) or biologics targeting specific cytokine pathways [14]. Such combinations could provide synergistic effects, particularly in refractory cases.

In summary, these case reports provide real-world evidence of the long-term effectiveness and safety of ILI in patients with OLP resistant to both topical and systemic corticosteroids. This approach offers a practical and accessible treatment option, especially in challenging clinical scenarios. Furthermore, its suitability for patients with systemic conditions, such as diabetes, enhances its clinical utility. Repeated injections, where necessary, can further optimize outcomes, reducing the risk of follow-up loss and ensuring better long-term management. Future studies should focus on optimizing ILI protocols and investigating alternative novel therapies or combination therapies to further enhance the management of refractory OLP.

No potential conflict of interest relevant to this article was reported.

Data sharing is not applicable to this article because no new data were created or analyzed in this study.

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2022R1F1A1075363).

Conceptualization: SY, YP, HJA. Data curation: SY, YP. Formal analysis: SY, MC, JSK. Funding acquisition: HJA. Methodology: SY, YP, JSK. Project administration: HJA. Visualization: SY. Writing - original draft: SY. Writing - review & editing: YP, JK, MC, JSK, HJA.