The effect of mycophenolate mefitil on oral erosive lichen planus lesions

Background and objectives: Lichen Planus is a relatively common inflammatory disease with an unknown etiology, and especially its ulcerative type is known as a premalignant disease. But despite this, there is still no known treatment for it. One of the new drugs that has attracted the attention of some researchers is Mycophenolate Mofetil (MMF). The effect of this drug orally on some diseases such as Pemphigus, pemphigoid, crown's disease, psoriasis, lupus erythematosus, erosive lichen planus have been investigated before. But so far, no research has been done on the effect of its adhesive mucus on ulcerative oral lichen planus. Therefore, in this research, the therapeutic effect of the drug mycophenolate mefitil on the adhesive mucosa on the size of the wound, pain, and burning in patients with oral erosive lichen planus was investigated.

Materials and methods: In this clinical trial study, 27 patients with oral lichen planus referred to the Department of Oral and Maxillofacial Diseases of Tabriz Faculty of Dentistry who were willing to cooperate were selected. Among these patients, 10 had bilateral ulcerative ulcers and were included in the study as a double-blind case-control study (first group). In 17 patients, the lesions on both sides were not identical and congruent, and they only had ulcerative ulcers on one side, and they were included in the study before and after (the second group). Then, in the first group, for 4 weeks, each patient was prescribed the drug "2% MMF adhesive mucus" on one side and the drug-free mucus adhesive on the other side. In the second group, only MMF adhesive mucus medicine was used on the wound in the order mentioned. The degree of burning of the lesions was measured and recorded by VAS (Visual Analogue Scale), the size of the lesions using a digital caliper, at the beginning of the treatment and weekly during the four weeks of treatment, and their changes were checked. During the treatment, 2 people from the first group and 2 people from the second group did not want to cooperate due to the distance and lack of ability to travel during the weekly follow-ups and therefore were excluded from the study. The data obtained from the study were analyzed using the statistical software SPSS v.16 and the paired t-test statistical method.

Findings: In the first group, there was a significant difference in terms of burning (P value=0.012) and in terms of wound size (P value=0.004). On the control side, at the beginning of the treatment vans, there was a significant difference in terms of the degree of burning (P value=0.048), but in terms of the size of the wound (P value=0.21), the difference was insignificant. In the comparison of the case and control side in the first group, there was a significant difference in terms of the size of the wound in the fourth week. In the second group, there was a significant difference in the amount of burning (P value = 0.004) and in terms of the size of the wound (P value = 0.002). No side effects of medication were reported by the patients.

Conclusion: Mycophenolate Mefitil 2% mucus adhesive drug is effective in reducing the clinical symptoms of ulcerative oral lichen planus (including wound size, pain, and burning), and this effect is dependent on the duration of treatment.

Key words: lichen planus Ulcerative, mycophenolate mefitil, sticky mucus, pain and burning

Lycan plan is a common chronic immunological lesion in the skin, mucous membrane, nails and hair follicles (1) during which self-reactive T lymphocytes against the antigens of the basal layer of the mucosa are activated and cause its degeneration. This lesion can range from a mild inflammation to the destruction of the epithelium and Painful wounds progress (2), but so far no method has been found for its complete treatment. The most common drugs used for this lesion are local and systemic corticosteroids (3). The prevalence of the oral type of the disease varies from 0.5 to 2.2 percent. However, oral lichen planus (OLP=OLP) consists of two components, white and red. The white and red parts of the lesion can be reticular, papular, plaque-like, bullous, erythematous, and ulcerated (2). Activated T lymphocytes play an essential role in the pathogenesis of lichen planus, and with lymphocytic infiltration, they destroy keratinocytes and form mucosal lesions.The drug Mycophenolate Mofetil (MMF), which is widely used in organ transplant patients to prevent transplant rejection, is an immunosuppressive drug and specifically inhibits the function of T lymphocytes (4). It plays a key role in de novo (de novo) guanosine nucleotide resynthesis, and its inhibition causes a decrease in guanosine nucleotides and an increase in adenosine nucleotides, and subsequently, DNA synthesis and cell proliferation are inhibited. Due to the dependence of active lymphocytes on the de novo synthesis pathway, mycophenolic acid has a significant cytostatic effect on them. So far, this drug has been successful in the treatment of various skin diseases, including lichen planus and autoimmune rheumatic diseases, especially lupus (5). Recently, such immunosuppressive drugs are used in order to reduce the dose and, as a result, reduce the side effects of corticosteroid drugs in the treatment of autoimmune vesicolobular diseases (6).

The oral form of this drug has been used in the treatment of pemphigus vulgaris, bullous pemphigoid, pemphigus foliaceus, Crown's disease and psoriasis, and it has been considered a safe and completely effective drug (7). In a research, the efficacy of 1% MMF eye drops has been investigated in animal studies and the topical use of this drug after corneal transplant surgery has been found to be useful. It is combined with cyclosporine and then 2 grams daily for two months and 1.5 grams daily for the next two months, resulting in a complete recovery in the ulcerative areas of lichen planus lesions (10). It has much less renal, hepatic and nervous effects and is well tolerated in skin treatments (11) and the occurrence of short-term or long-term side effects has not been reported, except for a small digestive reaction (4), of course, all these side effects are related to the oral form of this drug. However, due to the special conditions of the mouth such as the presence of saliva and the impossibility of easy access to all lesions, in this study the method of drug delivery to the mucous membrane of mycophenolate mefitil oral adhesive was used. Due to the concentration of the drug in the damaged area, a much lower dose of the drug is used. All these cases are among its advantages over other similar drug delivery methods such as solutions, gels, ointments, and oral sprays (12).

Therefore, considering the effectiveness of MMF on lichen planus and the few reported side effects of MMF, as well as the advantages of using the mucoadhesive drug delivery method, the purpose of this review is to use the mucoadhesive form of the drug. For the first time, mycophenolate mefitil is effective in reducing the symptoms of oral lichen planus lesions, which is evaluated in a sample of the Iranian community.

Project assumptions:

Mycophenolate mefitil mucosal adhesive has no effect on the burning and size of ulcerative lichen planus lesions.