Oral lichen planus. Treatment of symptomatic lesions

About the project

Aim

The overall aim is to investigate the effect of mouth rinsing with extra-strong corticosteroids in symptomatic oral lichen planus and to investigate the risk of malignancy development in patients with oral lichen planus treated with topical corticosteroids.

Background

Oral lichen planus (OLP) is a relatively common disease of the oral mucosa. The cause of the disease is an autoimmune reaction that gives rise to chronic inflammation in the mucous membrane. The prevalence is 1.2%. The symptoms vary, from burning when eating spicy food to long-term pain with significantly reduced quality of life as a result. The disease is characterized by recurrent remissions and exacerbations. Complete healing is rare and there is a risk of developing squamous cell carcinoma developing in the oral mucosa. Many different drugs have been tried in the treatment of OLP but no cure has been found. The treatments provided aim to reduce the inflammatory reaction and thereby relieve the patient's symptoms. The scientific basis is insufficient to be able to assess whether any drug is better than another. Lichenoid lesions of the oral mucosa are often infected with candida. The candida infection causes symptoms similar to lichen lesions (burning). The most common side effect of topical steroid treatment is oral candidiasis. The risk of squamous cell carcinoma arising from OLP is usually estimated at 0.3%. The drugs usually used in OLP affect the immune system. Long-term treatment could thus contribute to mutated tissue and the development of dysplasia and squamous cell carcinoma.

Project description

Study I

Aim

To examine the effect of mouth rinsing with an extra-strong corticosteroid compared to a placebo in symptomatic OLP.

Material and method

The study will be conducted as a multicentre clinical study, randomized and double-blinded, and according to a standardized method (SPIRIT). The study will include 90 patients with oral lichen planus who are eligible for symptom-relieving treatment and will be conducted at the Faculty of Odontology, University of Malmö and Department of Oral and Maxillofacial Surgery, Skånes University Hospital Clinic Lund, Region Skåne. No advertising for research persons will take place. Only patients who are referred to the clinics where the study is to be performed will be eligible for inclusion. Primary efficacy variable: Clinical appearance of the lichen lesion. Assessment with a scoring system (Site-score, Severity-score, Activity-score). Secondary effect variables: Quality of life (OHIP-14), Pain score (VAS), and Burning sensation score (VAS). Patients included will be allocated to either active treatment (clobetasol gel) in two different dosages or placebo (placebo gel). The investigational drug supplier (APL), which is independent of participating researchers, packages and labels all drug bottles according to a randomization list. The lichenoid lesions are documented with photographs. Biopsy 1 is taken at the time of examination (visit 1) from the lichen lesion to ensure a diagnosis according to the WHO. The biopsy is taken in a representative area of the lesion. Biopsy 2, taken during the treatment evaluation (visit 4), is in direct connection to the scar after the first biopsy and where the clinical improvement is most clearly visible.

Study II

Aim

To investigate the changes that can be seen histologically when treating symptomatic OLP with topical extra strong corticosteroid.

Material and method

The biopsies taken in Study I are used to make a diagnosis. In Study II, the same biopsies are used to evaluate the treatment effect in terms of the number of T-lymphocytes, degree of liquid fraction degeneration, epithelial thickness and presence of Civatte bodies. Immunohistochemical analysis is performed with respect to angiogenesis and amount of plasma cells. The clinical appearance of the lichen lesion and the patient's perceptions of symptoms recorded in Study I are linked to the histological image.

Study III

Aim

To investigate how the oral microbiological flora is composed and changes during treatment with a topical extra-strong corticosteroid.

Material and method

Specifically, we want to find out the presence of candida in patients with symptomatic OLP and which species it may be. Samples after treatment are analyzed with respect to changes in candida occurrence and the remaining patient's perceptions of symptoms. The effectiveness of treatment of candidiasis with Nystatin with varying intensity of topical steroid treatment is evaluated. Scrape and brush samples are collected from oral lesions in patients included in Study I. The scraping sample is performed with a sterile raspatorium and placed on a slide, smeared and fixed with 70% alcohol. PAS staining of the smear provides answers to the presence of fungal hyphae. With a cytobrush, surface debris from oral lesions is collected and stored after sampling in a -80 degree C freezer. The samples are analysed with sequencing to find out which candida species are present.

Study IV

Aim

To investigate the risk of malignancy development of OLP in patients treated with topical corticosteroids and to define the group of patients with OLP based on comorbidities such as mental illness, other autoimmune diseases, allergies and lichen disease outside the oral cavity.

Material and method

Patients (OLP cohort) will be identified through the Biobank at the Department of Oral Pathology, Faculty of Odontology, Malmö University. The Swedish National Prescribed Drug Register will provide information on the prescription of topical steroids (exposed OLP cohort). The Swedish National Cancer Register will be used to investigate whether steroid treatment increases the risk of lichen lesion malignancy. The Swedish National Patient Register will be used for investigation of the occurrence of mental illness, other autoimmune diseases, allergies and lichen disease outside the oral cavity in the OLP cohort and the control cohort. The persons in the control cohort will be randomly selected from the Swedish Longitudinal Integrated Database for Health Insurance and Labor Market Studies (LISA) in the proportions 2:1 and matched to the OLP cohort on gender and age.

Significance

If treatment with clobetasol gel proves to have a good effect on symptomatic oral lichen planus, this treatment can be recommended in care programs. Through studies at the tissue level, we wish to gain knowledge about how OLP is best diagnosed and whether different subgroups can be identified to optimize medical treatment. By studying candida occurrence in connection with OLP, we can gain knowledge about how the treatment of OLP can be optimized. Through the registry study, we can gain knowledge about the risk of malignancy development of OLP lesions and whether this risk increases during treatment with topical steroids. Furthermore, we can gain knowledge about possible co-morbidities in patients with OLP.