Clinical and Immunohistochemical Effect of Topical Pimecrolimus in Treatment of Oral Lichen Planus

Overview

Oral lichen planus (OLP) is a chronic disease characterized by periods of remission and relapse. Therapeutic objectives for OLP should be to quickly reduce disease symptoms by targeting pathophysiological pathways, and to provide long-term management by reducing recurrences. Pimecrolimus is a novel topical selective inflammatory cytokine release inhibitor; considering its mechanism of action it is reasonable to theorize that pimecrolimus may effectively treat OLP without the potential side effects that are associated with corticosteroids.

Lichen planus is a chronic, immunological, mucocutaneous disease, characterized by periods of remission and relapse1. Oral lichen planus (OLP) is one of the most common mucocutaneous diseases manifesting in the oral cavity, and the oral mucosa may be the only site of involvement 2, with variable incidence between 0.5% and 4% 3. Three major clinical forms of OLP (reticular, erosive/ ulcerative, and erythematous/atrophic) have been recognized, which could alternate and overlap in a dynamic state as disease progresses. Ulceration is the most severe form that it interferes with eating, speech, and swallowing. Erosive OLP lasts for years, resistance to treatment and spontaneous remissions are rare 4,5. Oral lichen planus is a T-cell-mediated chronic inflammatory oral mucosal disease. Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of OLP. Antigen-specific mechanisms include antigen presentation by basal keratinocytes to CD4+ helper T-cells that are stimulated to secrete the T helper -1 cytokines IL-2 and IFN-γ. Subsequently, CD8+ cytotoxic T-cells may be activated which then trigger basal keratinocyte apoptosis in OLP. While, non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions 6. The best known treatment of OLP remains high-potency topical corticosteroids7. However, corticosteroids are known to induce local atrophy, fragility, and telangiectasias, and to promote infections, including acute candidiasis. They also have theoretical risks of lowering local immunity, corticosteroids can exert their effects on the immune system by modulating transcription of genes in cells involved in immune response and other cell types; therefore this mode of action is not selective for the pathogenesis of lichen planus 8-10. A recent Cochrane review showed only little evidence for superiority of the assessed interventions over placebo for palliation of symptomatic OLP and recommended the need of randomized clinical trials on new therapies 11. Pimecrolimus a novel topical selective inflammatory cytokine release inhibitor; that binds to intra-cytoplsmic protein (macrophillin-12) subsequently inhibiting dephosphorylation of nuclear factor of activated T cells by calcineurin; this markedly reduces T-cell cytokine production. Given the T-cell-mediated pathogenesis of OLP, application of this calcineurin inhibitor seems to be a promising therapeutic option 12-14. Several case studies and open-label trials used topical pimecrolimus in treatment of OLP reported beneficial effects 12,15. Few prospective, randomized, vehicle-controlled studies have also been conducted and proved benefit of pimecrolimus over placebo 16,10,17. And one recent prospective study compared the effect of topical pimecrolimus with topical corticosteroid in treatment of OLP 18. The purpose of this study was to compare the effectiveness of topical pimecrolimus 1% with topical corticosteroid, in the treatment of oral erosive and atrophic lichen planus as a prospective, comparative clinical trial.

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