sirolimus and Lichen-Planus--Oral

Although superpotent topical corticosteroids are the first-line treatment for oral erosive lichen planus (OELP), topical rapamycin was found efficient in a previous case series.. To compare the efficacy and safety of topical rapamycin and betamethasone dipropionate ointment for OELP in a randomized, double-blind trial.. During a 4-year period, 76 patients were randomized and 75 received treatment (rapamycin, n = 39; betamethasone, n = 36). At 3 months, 39.4% of patients with betamethasone and 27.3% with rapamycin showed clinical remission (odds ratio 0.68, 95% CI [0.24; 1.89]; P = 0.46). Rates of remission after 1 and 2 months, reduction in pain and impact on food intake after 3 months, were higher with betamethasone than rapamycin. Recurrence of oral erosions was similar between groups. Adverse events occurred in 43.6% of patients with rapamycin (mostly burning sensation, impaired taste) and 27.8% with betamethasone (mostly oral candidiasis).. Although the study was limited by insufficient recruitment, we did not find any superiority of topical rapamycin over betamethasone dipropionate ointment for OELP. Given the rapid remission and pain improvement in the betamethasone group, it appears that superpotent topical corticosteroids should remain the first-line treatment for OELP.

Topics: Administration, Topical; Betamethasone; Double-Blind Method; Humans; Lichen Planus, Oral; Neoplasm Recurrence, Local; Ointments; Psoriasis; Sirolimus; Treatment Outcome

Chronic erosive oral lichen planus (CEOLP) is a painful disease. Topical steroids constitute the mainstay of treatment. Given the reports of a slightly greater risk of squamous-cell carcinoma, rapamycin may be a good candidate for recalcitrant CEOLP, as it has both immunosuppressive and antitumour properties.. To investigate the therapeutic effect and evaluate the blood absorption of topical rapamycin in patients with CEOLP.. We carried out an open prospective study: 7 women with CEOLP applied topical rapamycin (1 mg/ml) on oral erosive lesions twice a day for 3 months. Four patients also had erosive vulvar lesions and applied the same solution on both mucosae. We monitored blood sirolimus levels 15 days after the initiation of treatment. Complete remission was defined by the disappearance of oral erosions and partial remission when the surface of oral erosions was 50% less than the surface of the initial erosion.. At 3 months, 4 women had complete remission and 2 women had partial remission. One patient stopped treatment due to local discomfort. Only 1 woman had blood sirolimus levels that were detectable.. Topical rapamycin may be effective in some cases of refractory CEOLP, with negligible absorption into blood and minimal side effects.

Topics: Administration, Cutaneous; Aged; Antineoplastic Agents; Biopsy; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Middle Aged; Prospective Studies; Sirolimus; Treatment Outcome; Vulvar Lichen Sclerosus

Oral lichen planus (OLP) is a common T lymphocyte-mediated autoimmune disease of unknown etiology. The mammalian target of rapamycin (mTOR) can regulate proliferation, apoptosis, and autophagy of T lymphocytes, therefore impacting the T lymphocyte-mediated immunity. The present study was aimed to investigate the possible association between Akt/mTOR/4E-BP1 (eIF4E-binding protein 1) signaling, phospholipase D (PLD) and hypoxia-inducible factor 1 alpha (Hif-1α) in peripheral T lymphocytes of OLP and the correlation of their expression with the disease severity.. RAE (reticular, atrophic and erosive lesion) scores were used to assess the disease severity of OLP. Akt, mTOR, 4E-BP1, PLD1, PLD2 and Hif-1α expression in peripheral T lymphocytes were measured by using quantitative real-time polymerase chain reaction. Associations of Akt/mTOR/4E-BP1 expression with PLD1, PLD2 and Hif-1α expression were also assessed, respectively. Moreover, correlations of their expression with RAE scores were analyzed.. Expressions of mTOR, 4E-BP1, PLD2 and Hif-1α mRNA were significantly reduced in peripheral T lymphocytes of OLP patients, especially in erosive form. mTOR expression was positively correlated with PLD2 and Hif-1α expression in OLP. Moreover, mTOR, PLD2 and Hif-1α expression were negatively correlated with RAE scores, respectively.. Deregulated PLD2/mTOR/Hif-1α may contribute to the development of OLP and reflect the severity of the disease.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Apoptosis; Autophagy; Cell Cycle Proteins; Feedback, Physiological; Female; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lichen Planus, Oral; Male; Middle Aged; Phospholipase D; Phosphoproteins; RNA, Messenger; Severity of Illness Index; Signal Transduction; Sirolimus; T-Lymphocytes; TOR Serine-Threonine Kinases; Transcriptome; Young Adult