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Treating Oral Lichen Planus: current evidence and future perspectives

Monica Pentenero1*
  • 1 University of Turin, Department of Oncology, Oral Surgery Specialty School, Italy

Oral lichen Planus (OLP) is an inflammatory chronic disease. It is characterized by the potential occurrence of long-lasting symptoms due to the known immune-mediated pathogenesis and by an increased risk to develop oral squamous cell carcinoma. At present a definitive cure for OLP is still lacking and OLP patients are followed-up aiming at controlling symptoms and aiming to achieve an effective secondary prevention of oral squamous cell carcinoma. The presence of symptoms follows fluctuation in disease activity and pain or discomfort are usually observed in presence of atrophic and/or erosive areas, while reticular or popular forms are symptoms free. Current treatments are basically symptomatic, aiming to improve the quality of life of OLP patients without any curative intention. In fact, improving pain/discomfort as assessed by patient can be considered the primary aim of intervention, while improving the clinical presentation of the disease in terms of extension and severity (degree of erosion, erythema and reticulation) is a secondary aim. A recent randomized, placebo-controlled, double-blind trial (Arduino et al., 2018) investigating the effectiveness of clobetasol propionate 0.05% in the treatment of oral lichen planus enforces previous evidence supporting the use of topical steroids as the first-line treatment for symptomatic OLP (Thongprasom et al., 2011;Gupta et al., 2017). In 2011 a Cochrane review summed up evidence from 28 Randomized Controlled Studies (RCTs) that overall were able to identify topical steroids as the first-line treatment aiming at controlling OLP symptoms (Thongprasom et al., 2011). Conversely effectiveness in favouring healing of atrophic/erosive areas was assesses in only 15 out of 28 studies. Corticosteroids act by inhibiting the activation of dendritic cells and T-cells and by modulating the secretion of cytokines. Midpotency (e.g. triamcinolone acetonide) or high-potent (e.g. fluocinonide acetonide) or superpotent (e.g. clobetasol propionate) topical steroids have been investigated in clinical studies. Superpotent steroids could be preferred even if there is no evidence that any specific steroid is more or less effective at reducing pain compared to another type or dose of steroid. Conversely the time of contact of medication with the lesion is an important issue to achieve an effective treatment. Of interest, when searching the current literature on oral lichen planus, a large rate of studies investigated new carriers for topical treatments. A systemic rather than topical administration of steroids does not offer significantly better outcome, so that such approach (based on the use of prednisone or prednisolone) represents a second-line therapy and it should be reserved for multiple or widespread lesions, refractory cases, or in presence of extraoral sites of involvement. In patients unresponsive to steroids, calcineurin inhibitors (cyclosporin, tacrolimus or pimecrolimus) could represent a second-line treatment thanks to their different pharmacodynamics mechanism. In fact, they act by directly inhibiting the first phase of T-cell activation and by inhibiting expression of interleukins. They have also been shown to prevent release of cytokines and mediators of inflammation from mast cells. When considering the primary aim of OLP treatment, calcineurin inhibitors do not provide additional benefit from steroids and results were comparable to those of steroids. As for steroids, they are preferentially topically administered even if they can be responsible of a transient burning sensation. Of note, a potential cancer risk from the prolonged use of tacrolimus has been reported. Even if topical calcineurin inhibitors (TCI) do not seem to be superior to topical steroids, in recent years (2016-2018) most of studies investigating drugs for OLP treatment deal with TCIs. Retinoids (e.g. topical tocopherol) act by modulating the function on inflammatory and immunocompetent cells, including T-cells and macrophages. They are less effective than steroids for management of erosive OLP with scarce evidence about their effectiveness in reducing the discomfort or the length of the lesions in the oral cavity. Evidence about the effectiveness of other immunosuppressive drugs as mycophenolate motefil (MMF), methotrexate (MTX), azathioprine (AZA) or dapsone does not come from RCTs. As they exert anti-inflammatory effects through pharmacodynamics mechanisms different from steroids or calcineurin inhibitors, their use has been suggested in case of unresponsive patients. In recent years we have witnessed a growing interest for the use of laser devices in the management of OLP symptoms. Most of studies investigated the effectiveness of photobiomodulation obtained thanks to the Low Level Laser Therapy (LLLT) (Akram et al., 2018a), others assessed the effects of photodynamic therapy (PDT) (Akram et al., 2018b). Such non-pharmacological approach able to avoid drug-associated adverse effects, could represent an interesting future perspective when considering that OLP is a chronic disease. On the other hand, patients have to be submitted to a quite high number of LLLT sessions in order to have a significant improvement and it is rather difficult to determine the minimum number of sessions needed to achieve a good outcome. If LLLT sessions could well represent a more “patient-friendly” treatment when compared to the application of topical steroids, the high number of sessions could impair the patients’ compliance and it could represent a heavy workload for oral medicine clinics. Trying to achieve evidence from the literature, the presence of many variables related to the use of LLLT (laser wavelengths, power, spot size, or duration of laser exposure) could make meta analyses really intricate if not impossible. Finally, the effectiveness of LLLT in improving OLP symptoms as compared to steroid therapy is still debatable and the current evidence is not able to support LLLT as a first-line treatment in place of topical steroids. A few RCTs investigating the effects of nutriceuticals had already been assessed in 2011 by Cochrane reviewers. There was weak evidence supporting the use of aloe vera and one RTC reported that curcumin at dose of 6000 mg per day was efficacious with no side effects for management of OLP. Still in recent years, looking at the literature, researchers seem interested in the potential use of nutriceuticals as curcuminoids, chamomile, paeony capsule or propolis as alternative treatment in order to avoid side effects and to improve patients’ compliance. Quite recently a substantial increase in the development, validation and application of patient-reported outcome measures (PROMs) lead to a direct assessment of the subjective perception of the impact of the disease from patient’s perspective (Wiriyakijja et al., 2018). The introduction of such measures along with scales for the assessment of the intensity of symptoms (e.g. the visual analogue scale) and clinical scoring systems could enrich the results of RCTs when assessing the effectiveness of treatments.

References

1. Akram, Z., Abduljabbar, T., Vohra, F., and Javed, F. (2018a). Efficacy of low-level laser therapy compared to steroid therapy in the treatment of oral lichen planus: A systematic review. J Oral Pathol Med 47, 11-17. 2. Akram, Z., Javed, F., Hosein, M., Al-Qahtani, M.A., Alshehri, F., Alzahrani, A.I., and Vohra, F. (2018b). Photodynamic therapy in the treatment of symptomatic oral lichen planus: A systematic review. Photodermatol Photoimmunol Photomed 34, 167-174. 3. Arduino, P.G., Campolongo, M.G., Sciannameo, V., Conrotto, D., Gambino, A., Cabras, M., Ricceri, F., Carossa, S., Broccoletti, R., and Carbone, M. (2018). Randomized, placebo-controlled, double-blind trial of clobetasol propionate 0.05% in the treatment of oral lichen planus. Oral Dis 24, 772-777. 4. Gupta, S., Ghosh, S., and Gupta, S. (2017). Interventions for the management of oral lichen planus: a review of the conventional and novel therapies. Oral Dis 23, 1029-1042. 5. Thongprasom, K., Carrozzo, M., Furness, S., and Lodi, G. (2011). Interventions for treating oral lichen planus. Cochrane Database Syst Rev, Cd001168. 6. Wiriyakijja, P., Fedele, S., Porter, S.R., Mercadante, V., and Ni Riordain, R. (2018). Patient-reported outcome measures in oral lichen planus: A comprehensive review of the literature with focus on psychometric properties and interpretability. J Oral Pathol Med 47, 228-239.

Keywords: Oral lichen planus (OLP), Treatment, Steroids, calcineurin inhibitors, Low level laser therapy ( LLLT), Patient-reported outcome measures

Conference: 5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine., Ancona, Italy, 19 Oct - 20 Oct, 2018.

Presentation Type: oral presentation

Topic: Oral Diseases

Citation: Pentenero M (2019). Treating Oral Lichen Planus: current evidence and future perspectives. Front. Physiol. Conference Abstract: 5th National and 1st International Symposium of Italian Society of Oral Pathology and Medicine.. doi: 10.3389/conf.fphys.2019.27.00084

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Received: 27 Nov 2018; Published Online: 09 Dec 2019.

* Correspondence: Prof. Monica Pentenero, University of Turin, Department of Oncology, Oral Surgery Specialty School, Turin, Piedmont, 10124, Italy, marcomascitti86@hotmail.it