Clinical and Immunohistochemical Effect of Topical Pimecrolimus in Treatment of Oral Lichen Planus
Condition: Oral Lichen Planus
MeSH terms: Lichen Planus, Oral; Lichen Planus
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Pimecrolimus 1% cream; Betamethasone 17-valerate 0.1% cream
Intervention type(s): Drug; Drug
Intervention description(s): Patients were instructed to apply a thin layer of mixed equal amounts (½ ml) of the study medication and the adhesive gel base per application guided by the graduation on the plastic syringe on the oral lesions, 4 times daily, for a total of 1month. The patients were asked not to eat, drink, for 30 minutes after each application.; Patients were instructed to apply a thin layer of mixed equal amounts (½ ml) of the study medication and the adhesive gel base per application guided by the graduation on the plastic syringe on the oral lesions, 4 times daily, for a total of 1month. The patients were asked not to eat, drink, for 30 minutes after each application.Topical antifungal Miconazole 2% gel (Miconaz, oral Medical Union Pharmaceutical, Cairo, Egypt) was applied only in the fourth week of treatment period to avoid secondary candidiosis
Intervention MeSH terms: Betamethasone; Betamethasone Valerate; Betamethasone-17,21-dipropionate; Betamethasone benzoate; Pimecrolimus; Betamethasone sodium phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment