tacrolimus and Lichen-Planus--Oral

Tacrolimus is a powerful macrolide calcineurin inhibitor that has low adverse effects which lead to a rapid response in the control of signs and symptoms in comparison to that of corticosteroids in Oral Lichen Planus(OLP). There have been increasing number of studies establishing the use of topical tacrolimus in oral lichen planus. Still, there is a need to find evidence of the successful use of tacrolimus in comparison to other drugs used in the treatment of OLP, by means of a systematic review and meta-analysis, so that an informed and accurate approach can be utilized.. A comprehensive literature review was performed, including PubMed, the Cochrane Library, published up to and including December 2021. There were no restrictions on date of publication. Articles available in English language were included. Using the Cochrane Collaboration tool, we assessed the risk of bias for randomized controlled trials. A meta-analysis was performed on the relevant studies.. A total of 11 RCTs evaluating the effects of tacrolimus were included in this study after application of inclusion and exclusion criteria. Seven studies revealed a low bias risk, three presented a moderate risk and one had a high risk of bias. The results revealed no significant difference in clinical resolution and adverse effects between tacrolimus and corticosteroids. The pooled data from our meta-analysis shows that there is not sufficient evidence to prove that Tacrolimus is better in efficacy than other topical corticosteroids.. According to the current systematic study and meta-analysis, there is not sufficient evidence to prove that Tacrolimus is better in efficacy than other drugs. Uniform trials are required with larger sample sizes and standardized methodology are required for a better analysis.

Topics: Calcineurin Inhibitors; Drug-Related Side Effects and Adverse Reactions; Humans; Lichen Planus, Oral; Macrolides; Retinoids; Tacrolimus

To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP).. A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with placebo or different active interventions for OLP management were considered.. Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone.. Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.

Topics: Administration, Topical; Calcineurin Inhibitors; Clobetasol; Cyclosporins; Dexamethasone; Fluocinonide; Health Care Costs; Humans; Lichen Planus, Oral; Steroids; Tacrolimus; Treatment Outcome; Triamcinolone

To examine the comparative efficacy and safety of topical administration for oral lichen planus.. An electronic database search (1st January 1946 to 1st May 2020) for randomised controlled trials identified 34 studies involving eight interventions (clobetasol, betamethasone, triamcinolone, dexamethasone, fluocinolone, tacrolimus, pimecrolimus, and cyclosporine); these studies were subjected to network meta-analysis using direct and indirect comparisons [efficacy indicators: clinical response rate, symptom-reducing effect (visual analogue scale score), sign-reducing effect (Thongprasom-scale score) and relapse; safety indicator: adverse event occurrence].. Compared with placebo, tacrolimus had the best clinical response rate (odds ratio (OR), 57.78 [95% CI 3.15-1060.52]; P-score, 0.8654) and cyclosporine had the worst (OR, 3.61[95% CI 0.20-66.62]; P-score, 0.2236); tacrolimus had the best symptom-reducing effect (standardised mean difference (SMD), 1.06 [95% CI 0.41-1.71]; P-score, 0.9323) and fluocinolone had the worst (SMD, -0.54 [95% CI -1.44-0.36]; P-score, 0.0157); dexamethasone had the best sign-reducing effect (SMD, 3.60 [95% CI 1.74-5.45]; P-score, 0.8306) and clobetasol had the worst (SMD, 2.63 [95% CI 1.66-3.61]; P-score, 0.2581); and pimecrolimus performed best (OR, 0.04 [95% CI 0.00-0.64]; P-score, 0.9227) and clobetasol performed the worst [OR, 0.60; 95% CI 0.15-2.45; P-score, 0.2545] in reducing relapse. Regarding safety, dexamethasone was the safest compared with placebo [OR, 0.37; 95% CI 0.05-2.57; P-score, 0.9337), whereas fluocinolone ranked low for safety [OR, 9.48; 95% CI 1.50- 60.03; P-score, 0.1189].. The relative ranking of topical administration varies according to the different indicators. Based on the joint consideration of clinical response rate and adverse event occurrence, dexamethasone, triamcinolone and betamethasone are recommended for better efficacy and safety. The optimal treatment for oral lichen patients varies under different conditions.

Topics: Administration, Topical; Betamethasone; Clobetasol; Humans; Lichen Planus, Oral; Network Meta-Analysis; Tacrolimus; Treatment Outcome

Symptomatic oral lichen planus is a common chronic T-cell-mediated disorder characterized by pain and inflammation. The meta-analysis aimed to compare and evaluate the effects and safety of tacrolimus for treating patients with symptomatic oral lichen planus.. A comprehensive literature review was performed, including PubMed, the Cochrane Library, Embase, and Web of Science published up to and including December 2020. ClinicalTrials.gov was searched for ongoing trials. There were no restrictions on language or date of publication. Using the Cochrane Collaboration tool, we assessed the risk of bias for randomized controlled trials and estimated the proportion of between-trial heterogeneity.. A total of 9 RCTs evaluating the effects of tacrolimus were included in this study. The results revealed no significant difference in clinical resolution and relapse between tacrolimus and corticosteroids. However, tacrolimus may be more likely to cause mild adverse effects. In particular, clinical resolution was not significantly different between tacrolimus and clobetasol propionate, and between tacrolimus and triamcinolone acetonide, while tacrolimus was more likely to cause adverse effects than triamcinolone acetonide and clobetasol propionate. Moreover, there was no significant difference in pain resolution between tacrolimus and clobetasol. Furthermore, adverse effects were not significantly different between tacrolimus and pimecrolimus.. This systematic review and meta-analysis of 9 clinical trials supported the short-term application of tacrolimus as an effective regimen in OLP patients resistant to other topical and systemic therapies. Furthermore, the adverse effects of tacrolimus were minor and transient and did not affect tacrolimus' continued application.

Topics: Administration, Topical; Calcineurin Inhibitors; Humans; Lichen Planus, Oral; Randomized Controlled Trials as Topic; Tacrolimus; Treatment Outcome

Oral lichen planus (OLP) is a relatively common chronic T cell-mediated disease, which can cause significant pain, particularly in its erosive or ulcerative forms. As pain is the indication for treatment of OLP, pain resolution is the primary outcome for this review. This review is an update of a version last published in 2011, but focuses on the evidence for corticosteroid treatment only. A second review considering non-corticosteroid treatments is in progress.. To assess the effects and safety of corticosteroids, in any formulation, for treating people with symptoms of oral lichen planus.. Cochrane Oral Health's Information Specialist searched the following databases to 25 February 2019: Cochrane Oral Health's Trials Register, CENTRAL (2019, Issue 1), MEDLINE Ovid, and Embase Ovid. ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. There were no restrictions on language or date of publication.. We considered randomised controlled clinical trials (RCTs) of any local or systemic corticosteroid treatment compared with a placebo, a calcineurin inhibitor, another corticosteroid, any other local or systemic (or both) drug, or the same corticosteroid plus an adjunctive treatment.. Three review authors independently scanned the titles and abstracts of all reports identified, and assessed risk of bias using the Cochrane tool and extracted data from included studies. For dichotomous outcomes, we expressed the estimates of effects of an intervention as risk ratios (RR), with 95% confidence intervals (CI). For continuous outcomes, we used mean differences (MD) and 95% CI. The statistical unit of analysis was the participant. We conducted meta-analyses only with studies of similar comparisons reporting the same outcome measures. We assessed the overall certainty of the evidence using GRADE.. We included 35 studies (1474 participants) in this review. We assessed seven studies at low risk of bias overall, 11 at unclear and the remaining 17 studies at high risk of bias. We present results for our main outcomes, pain and clinical resolution measured at the end of the treatment course (between one week and six months), and adverse effects. The limited evidence available for comparisons between different corticosteroids, and corticosteroids versus alternative or adjunctive treatments is presented in the full review. Corticosteroids versus placebo Three studies evaluated the effectiveness and safety of topical corticosteroids in an adhesive base compared to placebo. We were able to combine two studies in meta-analyses, one evaluating clobetasol propionate and the other flucinonide. We found low-certainty evidence that pain may be more likely to be resolved when using a topical corticosteroid rather than a placebo (RR 1.91, 95% CI 1.08 to 3.36; 2 studies, 72 participants; I² = 0%). The results for clinical effect of treatment and adverse effects were inconclusive (clinical resolution: RR 6.00, 95% CI 0.76 to 47.58; 2 studies, 72 participants; I² = 0%; very low-certainty evidence; adverse effects RR 1.48, 95% 0.48 to 4.56; 3 studies, 88 participants, I² = 0%, very low-certainty evidence). Corticosteroids versus calcineurin inhibitors Three studies compared topical clobetasol propionate versus topical tacrolimus. We found very low-certainty evidence regarding any difference between tacrolimus and clobetasol for the outcomes pain resolution (RR 0.45, 95% CI 0.24 to 0.88; 2 studies, 100 participants; I² = 80%), clinical resolution (RR 0.61, 95% CI 0.38 to 0.99; 2 studies, 52 participants; I² = 95%) and adverse effects (RR 0.05, 95% CI 0.00 to 0.83; 2 studies, 100 participants; very low-certainty evidence) . One study (39 participants) compared topical clobetasol and ciclosporin, and provided only very low-certainty evidence regarding the rate of clinical resolution with clobetasol (RR 3.16, 95% CI 1.00 to 9.93), pain resolution (RR 2.11, 95% CI 0.76 to 5.86) and adverse effects (RR 6.32, 95% CI 0.84 to 47.69). Two studies (60 participants) that compared triamcinolone and tacrolimus found uncertain evidence regarding the rate of clinical resolution (RR 0.86, 95% CI 0.55 to 1.35; very low-certainty evidence) and that there may be a lower rate of adverse effects in the triamcinolone group (RR 0.47, 95% CI 0.22 to 0.99; low-certainty evidence). These studies. Corticosteroids have been first line for the treatment of OLP. This review found that these drugs, delivered topically as adhesive gels or similar preparations, may be more effective than placebo for reducing the pain of symptomatic OLP; however, with the small number of studies and participants, our confidence in the reliability of this finding is low. The results for clinical response were inconclusive, and we are uncertain about adverse effects. Very low-certainty evidence suggests that calcineurin inhibitors, specifically tacrolimus, may be more effective at resolving pain than corticosteroids, although there is some uncertainty about adverse effects and clinical response to tacrolimus showed conflicting results.

Topics: Adrenal Cortex Hormones; Calcineurin Inhibitors; Clobetasol; Cyclosporine; Humans; Lichen Planus, Oral; Oral Health; Pain Management; Randomized Controlled Trials as Topic; Tacrolimus

TCS (topical corticosteroids) are the first-line drug in the treatment of oral lichen planus (OLP). However, the value of topical calcineurin inhibitors (TCI) including tacrolimus, pimecrolimus and ciclosporin for OLP is still controversial.. To compare the efficacy and safety of TCI vs. TCS for OLP.. The authors searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and four Chinese databases from 1950 to May 2018. The randomized controlled trials comparing TCI and TCS for OLP reported at least one of the following outcomes: improvement of clinical signs and/or symptoms, relapse, blood levels of TCI and adverse events.. Twenty-one trials involving 965 patients were included in the analysis. For the treatment of OLP (3-8 weeks), TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy. Tacrolimus-TCS resulted in similar outcomes, with relapse at 3 weeks to 6 months. Blood levels of TCI were usually undetectable. In addition, tacrolimus showed a statistically higher incidence of local adverse events than TCS for short-term treatment. A few systemic adverse events occurred in the tacrolimus and ciclosporin groups, but they were not serious.. The evidence for tacrolimus (n = 12), pimecrolimus (n = 3) and ciclosporin (n = 6) demonstrated that treatment with TCI may be an alternative approach when OLP does not respond to the standard protocols. Tacrolimus 0·1% should be the first drug of choice when selecting TCI for short-term treatment in recalcitrant OLP. Further well-designed trials are warranted to evaluate the long-term efficacy and safety of TCI. What's already known about this topic? The main topical drug for oral lichen planus (OLP) is topical corticosteroids (TCS). Patients with OLP who are not responsive to TCS or are at risk of adverse events from TCS need other alternative drugs. Topical calcineurin inhibitors (TCI), including tacrolimus, pimecrolimus and ciclosporin, have become a hot topic in a variety of mucocutaneous immune-mediated diseases. What does this study add? TCI including tacrolimus, pimecrolimus and ciclosporin were similar to TCS in efficacy for the short-term treatment of OLP. The local adverse events of tacrolimus were higher than with TCS. A few systemic adverse events were reported with TCI, but they were all tolerable and not serious. The limited evidence for pimecrolimus (three trials) and ciclosporin (six trials) requires further studies to evaluate the short-term and long-term efficacy and safety of TCI compared with TCS.

Topics: Administration, Topical; Calcineurin Inhibitors; Cyclosporine; Humans; Lichen Planus, Oral; Mouth Mucosa; Tacrolimus; Treatment Outcome

Management of oral lichen planus (OLP) is challenging and therapeutic options are limited. The use of topical tacrolimus has shown promising results. We reviewed our daily life experience with topical tacrolimus in OLP patients.. This retrospective unicentre study included all 21 patients with OLP, which were evaluated over a 53-month period and treated with topical tacrolimus. Patients were initially given a topical preparation of 0.1% tacrolimus twice daily. The response to treatment was assessed using a 4-point scale at month 2 and 6: complete response of affected area (CR), major remission (>50%, MR), partial remission (25-50%, PR) and either no response (<25%) or worsening. The pain score was also assessed using a 3-point scale.. Four of 21 patients (19%) showed a CR at month 2, whereas at month 6, 7 (33%) had a CR. For patients who reported MR (n = 2) and PR (n = 8) at month 2, the therapy was continued. Of those, at 6 months, three patients showed a CR, while four maintained a PR. The pain score improved during treatment. After 2 months of therapy, eight of 10 patients with an initial high pain score achieved a significant improvement. In patients starting with moderate pain an improvement was observed in one of seven patients. Overall, for three patients there was a complete loss of pain, while in nine there was a reduction. Except for transitory burning sensation and altered taste sensation, no relevant side-effects were reported.. This retrospective analysis confirms that topical tacrolimus is a valuable therapeutic option in severe or treatment-resistant OLP. Our findings in daily practice suggested nevertheless that the efficacy of topical tacrolimus is overestimated with regard to both complete response and pain reduction.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Pain; Pain Measurement; Retrospective Studies; Tacrolimus; Treatment Outcome

This study was carried out to assess and compare the efficacy of tacrolimus and clobetasol in the treatment of oral lichen planus (OLP). The Cochrane Central Register of Controlled Trials, PubMed, Scopus, Science Direct, Springer Journals, and Elsevier databases were searched using specific keywords relevant to the research question for articles published from 1998 to December 31, 2012. Finally, 15 articles that assessed the effects of tacrolimus, clobetasol, and pimecrolimus on improvements in OLP were reviewed. In addition, a meta-analysis of odds ratios (ORs) was carried out for data in 10 of the 15 articles. The results showed that the ORs for improvements in OLP in patients taking clobetasol or tacrolimus, compared with those taking placebo or other drugs, were 1.19 and 8.00, respectively. It appears that topical tacrolimus is an effective alternative to topical clobetasol and may be considered as a first-line therapy in the management of OLP.

Topics: Administration, Topical; Calcineurin Inhibitors; Clobetasol; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Prognosis; Severity of Illness Index; Tacrolimus; Treatment Outcome

To assess the efficacy and safety of topical tacrolimus for erosive oral lichen planus (EOLP).. Literatures published up to December 2013 were searched from PubMed, Embase, CENTRAL, Chinese BioMedical Literature Database (CBM), and System for Information on Grey Literature in Europe (SIGLE). All randomized controlled trials (RCTs) of topical tacrolimus for EOLP which compared with other interventions or a placebo were considered in this Meta-analysis. Two researchers collected data independently. The assessment of methodological quality was based on Cochrane Handbook and the materials were analyzed with the software Revman 5.2.5. The primary outcome measures were the symptoms (e.g. pain, discomfort) complained by patients. The secondary outcome measures included the improvement rate of clinical signs assessed by the investigators and the incidence of adverse effects (e.g. clinical candidiasis).. A total of 9 RCTs involving 476 patients were finally included. The pooled odds ratio (OR) of clinical improvement for topical tacrolimus vs. topical corticosteroids was 1.19 [95% confidence interval (CI): 0.64-2.22, I2: 44%]. Regarding to 0.1% tacrolimus and 0.03% tacrolimus, the pooled OR were 1.87 (95% CI: 0.60-5.82) and 1.47 (95% CI: 0.14-16.04) respectively in subgroup analysis. No serious adverse events were reported in topical tacrolimus group.. There was no evidence to support that topical tacrolimus for EOLP was more effective and safer than topical corticosteroids in this Meta-analysis. Clinical assessment criteria should be established and accepted by clinicians and researchers before further RCTs are undertaken.

Topics: Administration, Topical; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Randomized Controlled Trials as Topic; Tacrolimus

Oral Lichen Planus (OLP) is a common disease of unknown aetiology affecting oral mucosae by T-cell mediated chronic inflammation. OLP diagnosis is made by evaluating both clinical and histological criteria. Pharmacological treatment is useful in symptomatic cases. Life-long clinical follow-up is essential, due to low-risk of malignant transformation. In vivo Reflectance Confocal Microscopy (RCM) offers a real-time virtual biopsy of the being tissues and does not require surgical excision nor histopathological processing. RCM was used to capture OLP lesions in order to clinically differentiate them from other clinical entities.

Topics: Autoimmunity; Biological Factors; Cyclosporine; Diagnosis, Differential; Humans; Lichen Planus, Oral; Microscopy, Confocal; Retinoids; T-Lymphocytes; Tacrolimus

Tacrolimus is an immunosuppressive property approved for the treatment of atopic dermatitis. Studies have shown that topical tacrolimus is effective for a broad spectrum of mucocutaneous diseases, including oral lichen planus. The objective of this article is to review the pharmacology of tacrolimus, its usage in oral lichen planus, adverse effects and advantages of tacrolimus over other conventional drugs, thus making it a popular and alternative drug for the treatment of lichen planus.

Topics: Administration, Topical; Carcinogens; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Tacrolimus

Oral lichen planus (OLP) is a chronic mucocutaneous disorder commonly found in middle-aged women. Despite the progress in research and advance in knowledge on OLP, a successful management is still difficult to achieve. The main aim of OLP treatment is to control the symptoms of the affected patients. Steroids and other immunosuppressive drugs have been recommended and widely used in the treatment of OLP. Topical corticosteroids are the mainstay of OLP treatment, but strong evidence on their effectiveness is lacking. The effectiveness of alternative ways of managing OLP has been recently reported. Topical aloe vera, topical pimecrolimus and oral curcuminoids are the most promising of the new treatment modalities. Other interesting modalities are topically applied thalidomide and amlexanox. Nevertheless, the careful assessment between the risks and benefits of these drugs is crucial and larger and well-conducted trials need to confirm the above encouraging results.

Topics: Adrenal Cortex Hormones; Aloe; Curcumin; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Phytotherapy; Plant Preparations; Tacrolimus

Inflammatory mucosal disorders are treated conventionally with potent or superpotent topical corticosteroids. For more than 20 years, topical cyclosporine has been used in the management of oral mucous membrane affections. Recently other topically applied calcineurin inhibitors, namely tacrolimus and pimecrolimus, expanded the armamentarium for the treatment of inflammatory mucosal diseases. This chapter places its main emphasis on the efficacy and safety of topical calcineurin inhibitors in the management of different oral and genital conditions, including anogenital lichen sclerosus (LS), oral and genital lichen planus, plasma cell balanitis and vulvitis, mucous membrane pemphigoid and pemphigus vulgaris, all conditions having usually a protracted course, requiring long-lasting treatment. There is current evidence for the effectiveness of both pimecrolimus and tacrolimus in the topical treatment of inflammatory oral mucosal diseases and genital dermatoses, especially oral lichen planus and genital LS.

Topics: Administration, Topical; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Balanitis; Calcineurin Inhibitors; Carcinogens; Female; Genital Diseases, Female; Humans; Lichen Planus; Lichen Planus, Oral; Lichen Sclerosus et Atrophicus; Male; Mucositis; Paraneoplastic Syndromes; Pemphigoid, Benign Mucous Membrane; Pemphigus; Tacrolimus; Vulvitis

The search for new drugs capable of controlling the symptoms and signs of oral lichen planus (OLP) with minimal side-effects remains an important challenge.. A literature review is made to evaluate the effectiveness and safety of topical tacrolimus and pimecrolimus in the treatment of OLP.. A review was made of the studies published between 1999 and 2008 in relation to the topical application of tacrolimus and pimecrolimus in OLP.. The data obtained point to the need for larger randomized, placebo-controlled studies with carefully selected and standardized endpoints, to allow adequate comparison between treatments. The adverse effects were fundamentally of a local nature, and in particular included burning sensation in the application zone. All the studies consulted found the treatment to be effective over short periods of time, with lesion recurrences after suppression of the drug. The long-term safety remains to be established.. There is need for larger placebo-controlled, randomized studies with carefully selected and standardized outcome measures.

Topics: Administration, Topical; Calcineurin Inhibitors; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Peptidylprolyl Isomerase; Randomized Controlled Trials as Topic; Safety; Tacrolimus; Treatment Outcome

Topics: Administration, Topical; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Oral Ulcer; Tacrolimus; Treatment Outcome

Topical tacrolimus and pimecrolimus are indicated for treatment of atopic dermatitis, but they have been studied in many off-label uses. Double-blind and open studies have shown favorable results with topical tacrolimus and pimecrolimus in oral lichen planus. In 1 study of oral lichen planus, blood tacrolimus was detected in 54% of patients, but there were no signs of systemic toxicity. Double-blind and open studies of vitiligo have shown favorable results with tacrolimus in combination with excimer laser, especially for lesions over bony prominences and on extremities. Similarly, double-blind studies of vitiligo have shown favorable results when pimecrolimus is combined with narrow-band UVB, especially for facial lesions. Double-blind and open studies of psoriasis have shown favorable results for tacrolimus and pimecrolimus, especially for inverse psoriasis. Topical calcineurin inhibitors have been effective in many other cutaneous disorders, and further studies would help clarify their roles.

Topics: Administration, Cutaneous; Calcineurin Inhibitors; Child; Child, Preschool; Crohn Disease; Dermatitis, Atopic; Dermatologic Agents; Double-Blind Method; Female; Humans; Lichen Planus, Oral; Lupus Erythematosus, Cutaneous; Male; Off-Label Use; Psoriasis; Rosacea; Skin Diseases; Tacrolimus; Therapies, Investigational; Vitiligo

Oral lichen planus (OLP) is a chronic mucosal condition commonly encountered in clinical dental practice. Lichen planus is believed to represent an abnormal immune response in which epithelial cells are recognized as foreign, secondary to changes in the antigenicity of the cell surface. It has various oral manifestations, the reticular form being the most common. The erosive and atrophic forms of OLP are less common, yet are most likely to cause symptoms. Topical corticosteroids constitute the mainstay of treatment for symptomatic lesions of OLP. Recalcitrant lesions can be treated with systemic steroids or other systemic medications. However, there is only weak evidence that these treatments are superior to placebo. Given reports of a slightly greater risk of squamous cell carcinoma developing in areas of erosive OLP, it is important for clinicians to maintain a high index of suspicion for all intraoral lichenoid lesions. Periodic follow-up of all patients with OLP is recommended.

Topics: Carboxymethylcellulose Sodium; Carcinoma, Squamous Cell; Chronic Disease; Diagnosis, Differential; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Mouth Neoplasms; Precancerous Conditions; Steroids; Tacrolimus

The study compared the clinical effectiveness of topical Tacrolimus (TAC) in patches or gel with Triamcinolone acetonide (TRI) gel for erosive/atrophic oral lichen planus (OLP) and investigated the influence of these therapies on Caspase-3 expression as a marker of apoptosis.. Thirty patients were randomly assigned into three equal groups to receive either topical TAC 0.1% patch twice daily, topical TAC 0.1% gel, or topical TRI 0.1% gel four times daily for 8 weeks. Each patient's clinical score (CS), visual analogue scale (VAS), and total atrophic area (TAA) of the marker lesion were measured at baseline, 2, 4, and 8 weeks of treatment, as well as after 4 weeks of treatment free period. Caspase-3 expression and lymphocytic counts (LC) were assessed in pre- and post-treatment biopsied stained sections.. TAC patch resulted in a higher reduction in CS [- 14.00 (15.54%)] and VAS [- 70.21 (15.82%)] followed by TAC gel then TRI gel within the first two weeks. The reduction in VAS and TAA were significantly higher in TAC groups compared to TRI gel, although the difference between TAC treatment was not significant and this was observed throughout the treatment and follow-up periods. Caspase-3 expression increased in connective tissue in all groups. It decreased significantly within the epithelium in both TAC groups but increased in TRI gel. (LC) were significantly lowered with the TAC patch compared to other groups. The percentage change in Caspase-3 epithelial expression was significantly correlated to the CS, TAA, and LC.. Both TAC patch and gel significantly decreased pain and lesion size than TRI gel, with a significant reduction in Caspase-3 expression within the epithelium in comparison to the increase seen with TRI gel. The study protocol was registered at www.. gov (NCT05139667) on 01/12/2021.

Topics: Administration, Topical; Apoptosis; Caspase 3; Gels; Humans; Lichen Planus, Oral; Tacrolimus

To evaluate the effectiveness of two different therapies on oral lichen planus (OLP) treatment through the analysis of OLP symptoms and signs and to analyze the risk of side effects related to the adopted protocols.. Thirty-eight patients with OLP were selected according to van der Meij and van der Waal clinical and histopathological criteria. Through a randomized design, 19 patients received Tacrolimus 0.1% ointment (T group) and 19 an anti-inflammatory mouthwash (M group) composed of calcium hydroxide 10%, hyaluronic acid 0.3%, umbelliferone, and oligomeric proanthocyanidins. The patients were examined on a regular basis for OLP symptoms, signs, and disease severity score changes over a 3-month follow-up period.. Both treatments were effective in the reduction of OLP signs and symptoms. However, at 3 months (T3), in comparison with the M group, T group patients showed significantly lower mean values of OLP signs (p = 0.035), symptoms (p = 0.045), and disease severity scores (p = 0.041). Moreover, the Spearman test showed that there was a significant correlation between OLP signs and symptoms at each follow-up session in all patients.. Both treatments demonstrated a significant approach to control OLP. However, tacrolimus determined a more effective improvement in OLP signs and symptoms compared to anti-inflammatory mouthwash at 3-month follow-up.

Topics: Anti-Inflammatory Agents; Humans; Lichen Planus, Oral; Mouthwashes; Tacrolimus

Oral lichen plans (OLP) is a potentially malignant inflammatory mucocutaneous disease. CD133 is an investigated surface marker for cancer stem-like cells (CSCs) that may be involved in tumor initiation in head and neck carcinomas. We compared short-term clinical effectiveness of topical pimecrolimus as selective inflammatory cytokine release inhibitor with betamethasone cream for erosive/atrophic OLP and investigated the influence of this therapy on CD133 expression.. Thirty patients were randomly assigned into two equal groups to receive topical pimecrolimus (group I) or betamethasone (group II) four times daily for 4 weeks. A marker lesion in each patient were assessed at baseline using clinical score (CS) and visual analog scale (VAS) then at 1, 2, and 4 weeks and after 4 weeks of treatment-free period. CD133 expression was detected in pre- and post-treatment immunostained sections.. Both drugs showed a reduction in CS, VAS, and CD133 expressions after treatment termination (p < 0.001). Pimecrolimus-treated lesions showed significant higher 1st week reduction in severity (33.1% (22.2)), pain score (57.53% (14.27)), less recurrence in follow-up period and less CD133 expression by the end of the 1st 4 weeks compared with betamethasone.. Pimecrolimus showed earlier clinical response and less recurrence rate compared with standard topical corticosteroid in symptomatic OLP lesions, and both treatment reduced CD133-positive CSC population.. The study proved the benefits of topical pimecrolimus in early management of painful lesions of OLP and its ability to inhibit CSCs, suggesting a possible role in reducing risk of malignant transformation.

Topics: AC133 Antigen; Administration, Topical; Adult; Betamethasone; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Tacrolimus; Treatment Outcome

Oral lichen planus (OLP) is a common, chronic inflammatory disease of the oral mucosa. Although several studies have shown the efficacy of different treatment modalities, a definitive cure has not yet been established. The present trial compares the effectiveness of topically-applied clobetasol and tacrolimus in the symptomatic management of OLP.. A randomized, comparative, double-blind study with 68 patients (43 females, 25 males; mean age: 46.76 years) was undertaken. Patients were randomly divided into two groups of 34 patients each to receive topical tacrolimus 0.1% cream or clobetasol propionate 0.05% cream for 3 weeks.. After 3 weeks of treatment, the mean pain score dropped by 1.59 (right) and 1.53 (left) in the tacrolimus group, while in clobetasol group these values were 0.94 and 0.85, respectively. The mean scores for clinical appearance reduced by 1.18 (right) and 1.0 (left) in the tacrolimus group compared with a reduction of 0.5 and 0.26, respectively, in the clobetasol group. These reductions were statistically significant (P < .05).. The results suggest that tacrolimus 0.1% cream is an effective alternative to topical steroid and can be considered a first-line therapy in OLP. However, further studies are needed to confirm the effectiveness of this treatment before it is recommended for use in clinical practice.

Topics: Administration, Topical; Adult; Aged; Clobetasol; Double-Blind Method; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Sri Lanka; Tacrolimus; Young Adult

This study compared the therapeutic efficacy of steroidal and non-steroidal agents for treating oral lichen planus.. Forty patients with clinical and/or histologically proven oral lichen planus were randomly placed into four groups and treated with topical triamcinolone, oral dapsone, topical tacrolimus or topical retinoid for three months. Pre- and post-treatment symptoms and signs were scored for each patient.. Patients in all treatment groups showed significant clinical improvement after three months (p 0.05) and for topical retinoid vs topical tacrolimus (p > 0.05).. Non-steroidal drugs such as dapsone, tacrolimus and retinoid are as efficacious as steroidal drugs for treating oral lichen planus, and avoid the side effects associated with steroids.

Topics: Administration, Oral; Administration, Topical; Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Dapsone; Female; Humans; Lichen Planus, Oral; Male; Retinoids; Tacrolimus; Treatment Outcome; Triamcinolone

To carry out a double-blind randomized controlled trial (RCT) to compare the effectiveness of topical tacrolimus (TAC), triamcinolone acetonide (TRI), and placebo (PLA) in symptomatic oral lichen planus (OLP).. A clinical score (CS, range 0-130) was developed to measure the clinical signs and symptoms of OLP. Twenty-seven OLP patients with a CS of ≥20 were randomly allocated to receive 0.1% TAC ointment (n = 11), 0.1% TRI paste (n = 7), or Orabase. Tacrolimus and TRI were more effective (P = 0.012 and 0.031, respectively) than PLA in reducing the CS at week 3. No difference in the efficacy was noted between TAC and TRI (P = 0.997).. This pilot RCT provides evidence for the effectiveness of TAC and TRI over PLA in the management of OLP.

Topics: Administration, Topical; Adult; Aged; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Pilot Projects; Severity of Illness Index; Tacrolimus; Triamcinolone Acetonide

Oral lichen planus (OLP) is a T-cell-mediated disease characterized by immune-mediated basal cell degeneration releasing interleukins (ILs) such as IL-6 and IL-8 into the circulation. Their serum levels reportedly reflect disease activity. Although many therapeutic options are available, none are curative. We compared the efficacy of tacrolimus 0.1% ointment and pimecrolimus 1% cream in OLP and correlated with serum IL-6 and IL-8 levels before and after treatment. Forty patients with symptomatic OLP were randomized into two groups, to receive either topical tacrolimus 0.1% ointment or pimecrolimus 1% cream (twice daily for 8 weeks). Patients were assessed at 2, 4, 8, and 12 weeks. At each visit, objective improvement in the net clinical score (NCS), drug tolerability, and side effects were evaluated. Serum IL-6 and IL-8 levels were measured at baseline and at eight weeks. Baseline characteristics were comparable between the groups. The mean NCS declined from 10.9 ± 4.5 and 9.9 ± 4.6 at baseline to 5.4 ± 3.5 and 5.3 ± 4.2 at 12 weeks for tacrolimus and pimecrolimus group, respectively. At each visit, in both groups, the decline in mean NCS from baseline was statistically significant (P < 0.05) and so was the decline in mean serum IL-6 and IL-8 levels pre- and post-treatment. Pimecrolimus 1% cream seems to be as effective as tacrolimus 0.1% ointment. Serum IL-6 and IL-8 may act as markers of disease activity. However, future efforts are needed to objectify the use of serum interleukin levels in the disease severity index.

Topics: Administration, Topical; Adult; Analysis of Variance; Calcineurin Inhibitors; Chi-Square Distribution; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Interleukin-6; Interleukin-8; Lichen Planus, Oral; Male; Middle Aged; Prospective Studies; Risk Assessment; Severity of Illness Index; Single-Blind Method; Tacrolimus; Treatment Outcome

Oral lichen planus (OLP) is a chronic inflammatory disease, affecting nearly 1-2% of the population; Proposed therapies are usually symptomatic and numerous drugs have been used, but recently, it has been published that there is insufficient evidence to support the effectiveness of any specific treatment as being superior. To the best of our knowledge, direct evaluation of the efficacy of topically applied pimecrolimus and tacrolimus in the treatment of atrophic-erosive OLP, refractory to topical steroids, is still lacking.. To assess the efficacy and safety of topical calcineurin inhibitors for unresponsive OLP. An 8 week randomized, double-blind controlled trial, followed by a 6 month follow-up period. Patients were treated with either pimecrolimus 1% cream or tacrolimus 0.1% ointment, both mixed with an equivalent amount of 4% hydroxyethyl cellulose gel. The medications were to be applied twice daily for 2 months. Each patient was examined at the beginning of therapy, and then every 2 weeks during the treatment and every 3 months of follow-up. Main outcome measures were: (i) to compare the effectiveness of topically applied pimecrolimus and tacrolimus; (ii) to evaluate which is more cost-effective; (iii) to determine which drug is faster in reducing signs and symptoms and (iv) which gives the longest remission.. Thirty patients were involved in the study. Both drugs were effective at inducing clinical improvement, with no statistical difference. Pimecrolimus creams revealed a significantly better stability of the therapeutic effectiveness (P = 0.031).. Both medications would currently appear to be a treatment of choice for patients with unresponsive atrophic-erosive OLP. Pimecrolimus seemed to be more effective in providing long-term resolution of signs and symptoms. Future efforts are however needed to obtain more objective evidence of the benefit of these medications in the treatment of immunologically mediated oral mucosal lesion.

Topics: Administration, Topical; Double-Blind Method; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Tacrolimus

To evaluate the efficacy and safety of tacrolimus mouth rinse on the treatment of erosive and ulcerative oral lichen planus (OLP).. A randomized single-blind open trial of tacrolimus mouth rinse with dexamethasone as control was designed. The VAS and REU scoring system was utilized to compare the signs and symptoms. The scores and therapeutic effects were analyzed with SPSS 17.0 software package.. There was no significant difference in effective rate between the treatment group and control group (X(2)=0.295,0.413, P>0.01) at 4-week and 12-week after treatment. There was significant difference in REU scores between the 2 groups (P<0.01) 4 weeks after treatment.. Tacrolimus mouth rinse effects quickly and is worthy of application in the treatment of erosive and ulcerative OLP.

Topics: Administration, Topical; Humans; Lichen Planus, Oral; Mouthwashes; Single-Blind Method; Tacrolimus

Oral lichen planus (OLP) is a common disease of the oral mucosa with worldwide distribution and overall prevalence of 0.5-2.2%. Its etiology remains unclear, although the role of autoimmunity is supported by its association with other autoimmune diseases and the presence of auto-cytotoxic T cell clones in the lesions. Although many options for treating symptomatic OLP are available, no therapy is curative. This trial compared treatments with topical tacrolimus 0.1% ointment and topical clobetasol propionate 0.05% ointment. Forty patients with histologically proven symptomatic OLP were divided into two groups of 20 to receive clobetasol propionate (0.05%) ointment or tacrolimus (0.1%) ointment for eight weeks. Follow-up for all patients included three visits during the treatment course and one post-treatment visit. At each visit, objective improvement in the lesions was assessed by two independent investigators. The primary outcome measure was defined as the percentage of patients attaining complete response at eight weeks. Secondary outcome measures were the percentages of patients attaining complete or partial response at 8 and 12 weeks. Patient-observed improvement was evaluated at each visit. Demographic parameters and pretreatment disease characteristics were comparable between the groups. The mean net clinical score (NCS) declined progressively from baseline at each follow-up visit in both groups. In the clobetasol group, the mean NCS declined from 8.00 ± 2.65 at baseline to 2.00 ± 1.49 at 12 weeks. In the tacrolimus group, the mean NCS declined from 7.78 ± 3.25 at baseline to 1.31 ± 1.06 at 12 weeks. At each visit, the decline in mean NCS from baseline was statistically significant (P < 0.05) in both groups. Complete response rates of 40% and 70%, respectively, were achieved in the clobetasol and tacrolimus groups (P = 0.057). The percentages of patients reporting "good" or "very good" treatment responses at week 8 were 74% in the clobetasol group and 100% in the tacrolimus group (P > 0.05). No severe adverse events were reported. Tacrolimus 0.1% ointment is an effective alternative to topical steroid and may be considered as a first-line therapy in OLP.

Topics: Adult; Clobetasol; Double-Blind Method; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Ointments; Tacrolimus

To assess the efficacy and safety of topical pimecrolimus 1% cream in the treatment of oral erosive lichen planus.. A 6-week randomized, double-blind, vehicle-controlled phase followed by a 6-week open-label phase.. Outpatients of the Department of Dermatology, University of Utah.. Twenty-one patients with oral erosive lichen planus were randomized and treated with either pimecrolimus 1% cream or vehicle cream.. Pimecrolimus 1% cream, or its vehicle, were applied twice daily for 6 weeks to each side of the mouth with a 2×2 inch gauze pad folded in half and placed directly on the erosive lesion.. Efficacy was based on clinical evaluation of Investigator's Global Assessment (IGA) of the overall severity of the disease, erythema, measurement of the size of any target erosion in millimetres, and assessment of spontaneous pain. Blood levels of pimecrolimus were monitored in all subjects on day 0 and repeated on day 7.. Pimecrolimus 1% cream was superior to vehicle cream in reducing mean IGA, pain, and erosion size. For the vehicle group that entered the open-label phase, pimecrolimus 1% cream improved the mean IGA, pain, erosion size, and erythema. Pimecrolimus levels were detected in nine out of 10 of the pimecrolimus-treated subjects. These levels were consistently low. The pimecrolimus cream was well-tolerated. No clinically relevant, drug-related adverse events were reported.. Pimecrolimus 1% cream was superior to vehicle in reducing pain, erythema, decreasing erosion size, and improving overall severity of disease when compared with vehicle treatment.

Topics: Administration, Topical; Dermatologic Agents; Double-Blind Method; Humans; Lichen Planus, Oral; Tacrolimus

Erosive oral lichen planus (EOLP) is a T-cell mediated inflammatory disease leading to severe pain and impairment. As current therapies are of limited efficacy, application of calcineurin inhibitors is considered to be a potential option.. To investigate the efficacy of pimecrolimus cream 1% (Elidel) compared with vehicle cream in the treatment of EOLP.. Twenty patients were enrolled in a prospective, double-blind, randomized, vehicle-controlled trial and assigned to either pimecrolimus or vehicle group. Study medication was applied for 30 days followed by 30 days of observation without therapy. In case of unresponsiveness, treatment was continued for 30 days with open-label pimecrolimus. EOLP was monitored on days 0, 30 and 60. Safety was assessed by patient documentation, measurement of pimecrolimus levels and blood counts.. Within 30 days erosions cleared completely in seven of 10 patients treated with pimecrolimus and in two of 10 patients treated with vehicle. The clinical EOLP 'composite score' including mucosal erosions and pain sensation was significantly reduced in the pimecrolimus-treated group compared with vehicle (P = 0.025). In the three of 10 patients not responding to pimecrolimus, EOLP cleared after an additional 30 days of treatment with pimecrolimus. Following termination of the therapy, sustained remission of EOLP was detected in 83% of patients demonstrating long-lasting effects of pimecrolimus treatment. No severe adverse events were observed. In five patients pimecrolimus blood levels were detected, all of which stayed below 4 ng mL(-1).. Pimecrolimus cream 1% effectively treats EOLP with long-lasting therapeutic effects and is therefore a promising therapeutic option for EOLP.

Topics: Administration, Topical; Adult; Aged; Dermatologic Agents; Double-Blind Method; Female; Humans; Lichen Planus, Oral; Male; Middle Aged; Ointments; Prospective Studies; Tacrolimus

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease of unknown etiology. Usually asymptomatic, the disorder is occasionally complicated by extensive painful erosions. Topical corticosteroids are the mainstay of treatment, but a new topical therapy with tacrolimus has been described previously. The aim of the current study was to examine the expression of heat-shock protein 70 (HSP70) in biopsy specimens from 11 OLP lesions before and after topical treatment with tacrolimus. Immunostaining was performed with anti-HSP70 antibody as the primary layer. Clinically, there was a rapid improvement with topical tacrolimus treatment in 10 out of the 11 patients. The moderate increase in HSP70 expression after treatment with tacrolimus was not significant. It was concluded that topical tacrolimus has no effect on the expression of HSP70 in OLP.

Topics: Administration, Topical; Aged; Animals; Female; HSP70 Heat-Shock Proteins; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Mouth Mucosa; Rabbits; Tacrolimus

Existing clinical trials have shown that topical corticosteroids are often effective in the management of oral lichen planus (OLP). However, tacrolimus has recently been shown to be an effective treatment of OLP.. To compare the effectiveness of clobetasol and tacrolimus in the topical management of OLP.. In this randomized comparative double-blind study, 30 consecutive patients with oral lesions consistent clinically and histologically with OLP were recruited. The patients were divided into 2 groups to receive clobetasol 0.05% or tacrolimus 0.1% ointment and were treated for 6 weeks.. The profiles of mean lesion sizes and mean pain measures did not differ between the tacrolimus and clobetasol treatment groups.. We found tacrolimus to be as useful as clobetasol in treatment of OLP. We believe that up-to-date evidence indicates the effectiveness of tacrolimus in treating OLP.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Clobetasol; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Ointments; Tacrolimus; Treatment Outcome

Oral lichen planus (OLP) is considered to be an autoimmune disease of unknown aetiology that affects the mucosae, especially the oral cavity.. We compared tacrolimus 0.1% ointment and clobetasol 0.05% ointment for the treatment of OLP.. A total of 32 patients (20 females and 12 males; all white, Italian origin, mean age of 43.6+/-18.4 years; 16 patients per treatment group) were treated with tacrolimus or clobetasol ointment for 4 weeks in a randomized, double-blind, clinical trial. Pain severity, burning sensation, and mucosal lesion extension were assessed using a four-point scale.. At the end of the treatment period, symptom scores were significantly lower in the tacrolimus group than in the clobetasol group.. The results of this study suggest that tacrolimus 0.1% ointment is more effective than clobetasol propionate 0.05% ointment in the treatment of OLP. However, other studies are needed to confirm the effectiveness of this treatment before it can be recommended for use in clinical practice.

Topics: Adult; Anti-Inflammatory Agents; Clobetasol; Epidemiologic Methods; Facial Pain; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Ointment Bases; Saliva; Tacrolimus

To evaluate the efficacy of 1% pimecrolimus cream in treating oral erosive lichen planus and to assess its tolerance.. Double-blind randomized trial with placebo control.. Outpatients of the Department of Dermatology, University Hospital of Nice, from December 21, 2004, to April 19, 2005.. Fourteen consecutive patients with oral erosive lichen planus confirmed by histological examination and with a clinical score superior to 3. Of the 14 patients, 2 did not meet the inclusion criteria and 12 were enrolled in the trial.. The intervention was 1% pimecrolimus cream or its vehicle, which was applied on ulcerated lesions twice a day for 4 weeks.. The efficacy of the treatment was quantified using a 12-point clinical score. The blood level of pimecrolimus was analyzed on days 0 (baseline), 14, and 28.. In the placebo group, the mean score was 4.67 on day 0 vs 3.33 on day 28 (P = .22). In the pimecrolimus group, the mean score was 6.83 on day 0 vs 3.33 on day 28 (P = .04). In the pimecrolimus group, blood concentrations of pimecrolimus were always above the threshold (mean value, 2.84 ng/mL; extreme values, 0-6.19 ng/mL). Pimecrolimus cream was well tolerated, and only transient burning sensations were reported by some subjects. Each of the patients in the pimecrolimus group whose condition improved subsequently relapsed when assessed 1 month after treatment.. The 1% pimecrolimus cream seems to be an effective and well-tolerated treatment for oral erosive lichen planus. The finding of systemic levels of pimecrolimus after mucosal applications necessitates long-term study because it seems that long-term application is required to maintain clinical improvement.

Topics: Aged; Calcineurin Inhibitors; Double-Blind Method; Female; Humans; Lichen Planus, Oral; Male; Middle Aged; Ointments; Tacrolimus

Lichen planus is a common chronic inflammatory mucocutaneous disease, affecting 0.1% to 4% of the general population. There is no published randomized active control clinical trial on pimecrolimus for the treatment of oral lichen planus (OLP).. The purpose of this study was to compare the efficacy and safety of pimecrolimus 1% cream with triamcinolone acetonide 0.1% paste in treating OLP.. In this investigator-blinded parallel-group randomized clinical trial, 40 patients were randomly assigned in two equal groups to receive either pimecrolimus 1% cream or triamcinolone acetonide 0.1% paste 4 times daily for a total of 2 months and followed up for another 2 months. The patients were assessed for painful symptoms measured by visual analog scale, the Oral Health Impact Profile score, and objective clinical score. Nonparametric tests were used to assess the main outcomes. Intention-to-treat analysis was used.. Eighteen patients in pimecrolimus group and 17 patients in triamcinolone group finished the 4-month trial course. Both pimecrolimus and triamcinolone groups showed significant improvement in all measured efficacy end points throughout the visits. There was no significant difference between changes from baseline median values of pimecrolimus and triamcinolone groups after treatment termination in terms of visual analog scale score (-9.8 +/- 11.3 vs -8.4 +/- 18.3, P = .70), Oral Health Impact Profile score (-1.5 +/- 2.6 vs -1.6 +/- 2.1, P = .38), and clinical score (-0.7 +/- 0.6 vs -0.8 +/- 0.7, P = .86), respectively. Two patients in pimecrolimus group experienced prominent but transient burning sensation whereas none of the patients in triamcinolone group had any prominent adverse event (P = .24).. Blood levels in pimecrolimus group were not measured and carcinogenicity of pimecrolimus, especially in its long-term use for OLP, is yet to be determined.. This study showed that patients with OLP may benefit from both topical pimecrolimus and triamcinolone acetonide therapy with minimal side effects. Further studies should be conducted to assess the maintenance effects and long-term safety of both drugs (Cochrane skin group identifier: CSG TrialNo. 22).

Topics: Administration, Topical; Adult; Dermatologic Agents; Female; Glucocorticoids; Humans; Lichen Planus, Oral; Male; Middle Aged; Pain; Pain Measurement; Sickness Impact Profile; Single-Blind Method; Tacrolimus; Treatment Outcome; Triamcinolone Acetonide

Treatment of symptomatic oral lichen planus remains a challenging problem. This study compared the efficacy of topical tacrolimus ointment with triamcinolone acetonide ointment in patients with oral lichen planus. Twenty patients (group I) were treated with topical tacrolimus 0.1% ointment 4 times daily, and 20 (group II) were treated with triamcinolone acetonide 0.1% ointment 4 times daily. The clinical effect was graded after 6 weeks. In group I, 6 patients healed, 12 showed improvement and 2 showed no improvement. In group II, 2 patients healed, 7 improved and 11 showed no improvement. The most commonly reported side-effect in both groups was temporary burning or stinging at the site of application. Unfortunately, oral lesions recurred within 3-9 weeks of cessation of treatment in 13 of the 18 patients who had initially shown an improvement or were healed in group I and in 7 of the 9 patients in group II. Topical tacrolimus 0.1% ointment induced a better initial therapeutic response than triamcinolone acetonide 0.1% ointment. However, relapses occurred frequently within 3-9 weeks of the cessation of treatment.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Ointments; Prospective Studies; Tacrolimus; Treatment Outcome; Triamcinolone Acetonide

Oral lichen planus (OLP) is a common chronic inflammatory disorder with criteria of auto-reactive disease. Treatment consists on topical application of corticosteroids, vitamin A derivates or cyclosporin. Calcineurin inhibitors as tacrolimus and pimecrolimus decrease the production of cytokines and inhibit T-cell proliferation. These substances have recently been introduced for local therapy of chronic inflammatory skin disorders. The aim of our study was to evaluate the effectiveness and side effects of local pimecrolimus in OLP. A group of five patients with histological proven OLP were treated with topical pimecrolimus 1% ointment twice daily to the affected area. Prior to treatment and after 7, 14, 28 and 42 days the lesions were assessed clinically and by photographs. The discomfort scores were evaluated by visual analogue scale (VAS) weekly. All five patients (median age 65.6 years) were female and showed involvement of the buccal mucosa. All lesions showed a reduction of inflammation activity during the treating period. The VAS scores decreased significantly under treatment (p=0,0014). Pimecrolimus ointment was tolerated well with no signs of itching or burning. However, 4 out of 5 patients complained about the reduced adherence properties of the cream. Although no complete remission of OLP has been observed in our series, signs of inflammatory activity of OLP as redness and burning sensations were reduced by topical pimecrolimus. Further controlled randomized studies have to be conducted to compare topical pimecrolimus with topical corticosteroid as standard therapy. The adherence properties of pimecrolimus 1% cream should be improved for intra-oral application.

Topics: Administration, Topical; Aged; Anti-Inflammatory Agents, Non-Steroidal; Dermatologic Agents; Female; Humans; Lichen Planus, Oral; Middle Aged; Mouth Mucosa; Pain Measurement; Tacrolimus; Treatment Outcome

The aim of our study was to evaluate the clinical efficacy and safety profile of a novel compound, Tacrolimus powder in Orabase 0.1% in patients with LP and LL.. Seven patients with LP and 3 with LL were asked to participate. All patients received a 1 week treatment of Fluconazole, prior to entering the study, and on follow up visit were provided with a 15 g container of the study medication. Patients were asked to treat the most symptomatic site, three times a day for two weeks.. Disease control (signs) was achieved in most patients by the end of two weeks (from 1.58 to 0.55); all patients experienced a high degree of discomfort (pain) at baseline, which dropped quickly by the end of the second week of treatment (from 1.95 to 0.45); none developed yeast during the course of treatment. Recurrent headaches were reported by one patient with erosive LP, and transient burning by a patient with reticular LP.. Tacrolimus powder in Orabase 0.1% appears to have a relatively safe profile, and represents a likely alternative to topical steroids in the treatment of LP and LL, especially in those at risk for oral candidiasis.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Carboxymethylcellulose Sodium; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Pain Measurement; Pharmaceutical Vehicles; Pilot Projects; Steroids; Tacrolimus; Treatment Outcome

The purpose of this study was to evaluate the efficacy, relative safety, and tolerability of 1% pimecrolimus cream in the treatment of oral erosive lichen planus (OELP).. Twenty patients with OELP were randomized into equal groups; group 1 applied 1% pimecrolimus cream twice daily to their oral lesions for 4 weeks, whereas group 2 applied a placebo cream. Photographs of the lesions were taken and analyzed for areas of ulceration, erythema, and reticulation. Discomfort scores were also assessed with a visual analogue scale (VAS). Blood samples were taken at baseline and at study completion; a complete blood count with differential and comprehensive metabolic panel was ordered. The Wilcoxon signed rank test was used.. The experimental group showed a decrease in ulceration (alpha = 0.068) and erythema (alpha = 0.005) at the mid-point with continued reduction of erythema at the final (alpha = 0.075) time measurement. The control group demonstrated an increase in reticulation at the mid-point (alpha = 0.017) and final (alpha = 0.007) time measurement. The VAS scores for the experimental group decreased during the study (alpha = 0.022). Blood levels were within the normal range.. The OELP lesion size in the 1% pimecrolimus group decreased and the pimecrolimus cream was found to significantly reduce the patient's pain scores. Further study of 1% pimecrolimus as therapy for OELP is warranted since it was shown to be effective, relatively safe, and well tolerated by patients within the limits of this short-term study.

Topics: Adult; Aged; Analysis of Variance; Double-Blind Method; Facial Pain; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Ointments; Pain Measurement; Pilot Projects; Statistics, Nonparametric; Tacrolimus

Erosive oral lichen planus is a chronic, painful disease that is frequently refractory to treatment. We describe 6 patients with erosive oral lichen planus, not responsive to topical steroids, who showed substantial improvement with the use of topical tacrolimus ointment 0.1%. This medication was well tolerated and appears to be effective in controlling erosive oral lichen planus.

Topics: Administration, Topical; Adult; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Tacrolimus; Treatment Outcome

Chronic erosive oral lichen planus (EOLP) is a severe form of lichen of the buccal mucosa that is often resistant to systemic or topical therapies.. To evaluate the efficacy and safety of topical tacrolimus, 0.1 mg per 100 mL of water, in treating EOLP.. Open-label, prospective, noncomparative study, with 6 months of treatment and 6 months of follow-up.. Dermatology department at a university hospital in Nice, France.. Ten patients with histologically proved EOLP that was refractory to treatment. Two patients were withdrawn because of noncompliance; findings in 8 were available for evaluation.. Mouthwashes with tacrolimus, 0.1 mg per 100 mL of distilled water, 4 times daily for 6 months.. Efficacy was assessed using a calculated score that combined the intensity of spontaneous and meal-triggered pain and the surface area of erosions. Safety assessment included the monitoring of adverse effects, clinical laboratory values, and blood concentrations of tacrolimus.. Among the 8 patients evaluated, 1 had no improvement and 7 were improved. The mean score decreased from 7.00 at baseline to 5.43 (a 22.43% decrease) at 1 month, 4.14 (a 40.86% decrease) at 2 months, 3.00 (a 57.14% decrease) at 3 months, 2.43 (a 65.29% decrease) at 4 months, 2.57 (a 63.29% decrease) at 5 months, and 3.43 (a 51.00% decrease) at 6 months. A decrease of symptoms was reported by the 7 responding patients as soon as the first month of treatment. No severe adverse effects were observed. All patients had whole-blood concentrations of tacrolimus below the detection limit of the assay (1.5 ng/mL) at all intervals. At 9 months, 6 patients had had a relapse within a mean of 38.6 days. At 12 months, all patients had had a relapse and required treatment with topical corticosteroids or systemic hydroxychloroquine sulfate.. Results of our study suggest a rapid and important palliating effect of low concentration of topical tacrolimus in distilled water in patients with EOLP.

Topics: Administration, Topical; Adult; Aged; Chronic Disease; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Lichen Planus, Oral; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Tacrolimus; Treatment Outcome

Our purpose was to investigate the efficacy and safety of 0.1% topical tacrolimus in erosive or ulcerative oral lichen planus.. This was an open-label, noncomparative study conducted in an outpatient oral medicine unit in London, United Kingdom. The study covered an 8-week period with a 22-week follow-up after cessation of therapy. Nineteen patients, aged 28 to 87 years with biopsy-proven oral lichen planus refractory to, or dependent on, systemic immunosuppressive agents, were enrolled. Seventeen patients (89%) completed the study. Application of 0.1% tacrolimus was administered to all symptomatic oral mucosal lesions. Clinical review took place 1, 3, 5, 7, and 8 weeks after commencing therapy. Alleviation of symptoms was evaluated by using a visual analogue scale as well as the McGill Pain and Oral Health Impact profile questionnaires. The extent of the oral mucosal erosion or ulceration was directly measured by the same clinician at all visits. Safety assessments included monitoring of adverse events, complete blood cell count, renal and hepatic clinical chemistry, and tacrolimus blood concentrations.. Tacrolimus caused a statistically significant improvement in symptoms within 1 week of commencement of therapy. A mean decrease of 73.3% occurred in the area of ulceration over the 8-week study period. Local irritation (in 6 subjects, 35%) was the most commonly reported adverse effect. Laboratory values showed no significant changes with time. Therapeutic levels of tacrolimus were demonstrated in 8 subjects but were unrelated to the extent of oral mucosal involvement. Thirteen of 17 patients suffered a relapse of oral lichen planus within 2 to 15 weeks of cessation of tacrolimus therapy.. Topical tacrolimus is effective therapy for erosive or ulcerative oral lichen planus.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Pain Measurement; Recurrence; Surveys and Questionnaires; Tacrolimus; Treatment Outcome

Oral lichen planus (OLP) is a chronic T cell-mediated mucocutaneous disease characterized by T cell infiltration at the connective tissue-epithelium interface. Traditionally, topical corticosteroids are used as the first-line drugs to treat OLP. However, long-term use of corticosteroids may lead to drug tolerance, secondary candidiasis, and autoimmune adrenal insufficiency. Although topical tacrolimus has often been recommended for short-term use in corticosteroid-refractory OLP, the precise role of tacrolimus in epithelial cells remains elusive. This study showed that tacrolimus could directly upregulate the expression of IL-37 in human gingival epithelial cells by promoting the TGF-βRI/Smad3 pathway independently of calcineurin inhibition and MAPKs. In contrast, dexamethasone, one of the corticosteroids, did not have the same effect. Moreover, IL-37 could inhibit the proliferation of activated T cells and the secretion of effector cytokines and alleviate epithelial cell apoptosis and death caused by activated T cells ina co-culturesystem. Furthermore, compared with healthy controls, IL-37 and p-Smad3 levels significantly increased in the oral mucosa affected by OLP, especially in the epithelium. IL-37 might have mediated a negative feedback mechanism to curb excessive inflammation in OLP. However, the expression of IL-37 was not associated with the infiltration of CD8

Topics: Adrenal Cortex Hormones; CD8-Positive T-Lymphocytes; Epithelial Cells; Humans; Lichen Planus, Oral; Tacrolimus; Up-Regulation

Abstract.

Topics: Administration, Topical; Clobetasol; Gingivitis; Humans; Lichen Planus, Oral; Tacrolimus; Treatment Outcome

Topical tacrolimus has been shown to be beneficial in the treatment of oral lichen planus (OLP). However, long-term effects and its optimal application protocol with gradual reduction have not been studied. Accordingly, we analysed the clinical response of OLP to tacrolimus in our daily clinical practice with a focus on the optimal long-term therapeutic scheme.. Retrospective analysis of all consecutive patients diagnosed with OLP and treated with topical tacrolimus (0.03% oral rinse) in a clinical setting between 2015 and 2020. The objective clinical response was measured by a 4-point scale (complete remission, major remission, partial remission and no response), and subjective impairment by a 3-point scale (severe, moderate and none).. Fifty-seven patients (74% women; median age: 66 years) were included. Fifty-six (98%) patients had prior treatment with topical steroids. After introduction of tacrolimus, objective remission (major or complete) was reached by 28%, 62%, 87% and 97% of patients after 3, 6, 12 and 24 months respectively. Subjective remission was reported by 16%, 48%, 69% and 83% after 3, 6, 12 and 24 months of treatment respectively. The treatment frequency could be gradually reduced from initially twice daily to once daily or less in 28%, 61%, 78% and 87% after 3, 6, 12 and 24 months respectively; 41% of patients completely suspended the treatment at one point, but 67% of them experienced a relapse after a median time of 3.3 months. Four patients (7%) developed a squamous cell carcinoma (SCC) during the observation period. Otherwise, there were only few and minor side-effects.. Topical tacrolimus can be an effective second-line therapy for OLP refractory to potent topical corticosteroids. The therapy frequency can often be reduced during the maintenance period. Both signs of clinical activity and subjective impairment should guide therapy. Regular follow-up is necessary to recognize possible SCC.

Topics: Administration, Topical; Aged; Carcinoma, Squamous Cell; Clinical Protocols; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Neoplasm Recurrence, Local; Retrospective Studies; Tacrolimus; Treatment Outcome

Topics: Humans; Lichen Planus, Oral; Metronidazole; Tacrolimus

Topics: Administration, Topical; Humans; Immunosuppressive Agents; Lichen Planus; Lichen Planus, Oral; Tacrolimus; Tympanic Membrane Perforation

Topics: Administration, Topical; Humans; Immunosuppressive Agents; Lichen Planus; Lichen Planus, Oral; Photosensitivity Disorders; Tacrolimus

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Diagnosis, Differential; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Pemphigoid, Benign Mucous Membrane; Retrospective Studies; Steroids; Tacrolimus

Topics: Calcineurin Inhibitors; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Tacrolimus

The current study will attempt to throw light on the role of desmoglein 1 and desmoglein 3 in the pathogenesis of erosive lichen planus and their response to topical application of tacrolimus.. Twenty patients with erosive oral lichen planus received tacrolimus ointment three times daily for eight weeks. Assessments using the clinical score and a visual analog scale were recorded at each visit. Serum concentrations of circulating autoantibodies to desmoglein 1 and desmoglein 3 will be determined by enzyme-linked immunosorbent assay (ELISA) at baseline, four weeks and eight weeks after treatment. Statistical software SPSS v.17.0 was used for statistical analysis.. All patients showed significant improvement in all outcomes within the follow-up periods when compared with the baseline (p < 0.05). The mean value of the visual analog scale were 8.30 ± 1.49, 4.15 ± 1.14, 2.10 ± 0.91, 0.90 ± 0.79, and 0.0 ± 0.0 starting from baseline to the end of follow up period. The mean value of the clinical score were 4.7 ± 0.48, 2.9 ± 1.29, 1.8 ± 1.32, 1.31 ± 0.69, and 0.69 ± 0.09 starting from baseline to the end of follow-up period. There was a significant decrease in the levels of anti-Dsg1 and anti-Dsg3, during the follow-up period (p < 0.05).. The concluded data suggest that antibodies against desmoglein 1 and desmoglein 3 seem to play a key role in the pathogenesis of oral lichen planus. Also, there is a significant decrease in the level of anti-Dsgl and anti-Dsg3 autoantibodies with topical tacrolimus 0.1% ointment.. Monitoring the serum level of antibodies against keratinocyte cadherins Dsg 1 and Dsg 3 can be used to evaluate the effect of topical application of tacrolimus on Erosive Oral lichen planus.

Topics: Administration, Topical; Adult; Autoantibodies; Biomarkers; Desmoglein 1; Desmoglein 3; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lichen Planus, Oral; Male; Middle Aged; Tacrolimus; Time Factors

Topics: Absorption, Physiological; Administration, Topical; Humans; Immunosuppressive Agents; Lichen Planus; Lichen Planus, Oral; Neoplasms; Tacrolimus

Topics: Administration, Topical; Humans; Immunosuppressive Agents; Lichen Planus; Lichen Planus, Oral; Tacrolimus

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.

Topics: Administration, Topical; Biopsy; Candidiasis, Oral; Carcinoma, Squamous Cell; Diagnosis, Differential; Diagnostic Errors; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Mouth Neoplasms; Surgical Flaps; Tacrolimus

Topics: Administration, Topical; Humans; Immunosuppressive Agents; Lichen Planus; Lichen Planus, Oral; Retrospective Studies; Tacrolimus

Pubmed, the Cochrane library, Scopus, Science Direct and two publishing company journals between 1998 and 2012.. Randomised controlled trials (RCTs) where the population included patients having OLP and the interventions were the use of clobetasol or tacrolimus compared to another intervention, while the outcome was improvement in clinical status.. Two authors working independently assessed for inclusion and performed data extraction. Quality was evaluated using Critical Appraisal Skills Programme (CASP) worksheets (http://www.casp-uk.net/). The treatment effect was calculated using OR and then pooled using a fixed model since heterogeneity was calculated as very low.. Ten studies were included; five studies involved clobetasol and five involved tacrolimus. Two meta-analyses were presented. The odds ratio for improvement for clobetasol was 1.21 (95%CI; 0.48 - 3.05) and 8.09 (95%CI; 3.77 - 17.38) for tacrolimus.. The authors concluded that using clobetasol or tacrolimus increases the odds of improvement of OLP lesions and therefore they are effective treatment for the condition, and go on to recommend tacrolimus as first-line therapy.

Topics: Clobetasol; Female; Humans; Lichen Planus, Oral; Male; Tacrolimus

Oral lichen planus (OLP) is an idiopathic T-cell-mediated mucosal inflammatory disease. Cathepsin K (Cat K) is one of the lysosomal cysteine proteases. It is involved in many pathological conditions, including osteoporosis and cancer. The expression and role of Cat K in OLP are unknown.. Twenty-five oral mucosal specimens diagnosed histopathologically as OLP and fourteen healthy controls (HC) were used to study the immunohistochemical (IHC) expression of Cat K. Colocalization of Cat K with CD1a, Melan-A, CD68, CD45, mast cell tryptase (MCT), and Toll-like receptors (TLRs) 4 and 9 were studied using double IHC and/or immunofluorescence (IF) staining. Expression of Cat K was also evaluated in OLP tissue samples before and after topical tacrolimus treatment.. Cat K was expressed in a higher percentage of cells in the epithelial zone, and the staining intensity was stronger in the stroma in OLP compared to controls (P < 0.001). In OLP, Cat K was present mostly in melanocytes and macrophages and sporadically in basal keratinocytes, endothelial cells, and extracellularly. Cat K was found also in some fibroblasts in HC and OLP samples. Coexpression of Cat K and TLRs 4 and 9 was seen in some dendritic cells (presumably melanocytes) and macrophages. In OLP, tacrolimus treatment reduced the expression of Cat K in the epithelium but increased it in the stroma.. These results suggest that Cat K is involved in the pathogenesis of OLP. Cat K possibly takes part in the modulation of matrix molecules and cellular receptors.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, CD1; Antigens, Differentiation, Myelomonocytic; Case-Control Studies; Cathepsin K; Female; Humans; Immunohistochemistry; Leukocyte Common Antigens; Lichen Planus, Oral; Male; MART-1 Antigen; Middle Aged; Mouth Mucosa; Tacrolimus; Toll-Like Receptor 4; Toll-Like Receptor 9; Tryptases; Young Adult

Topics: Aged; Erythema; Female; Humans; Immunosuppressive Agents; Lichen Planus; Lichen Planus, Oral; Middle Aged; Psoriasis; Scalp; Tacrolimus; Treatment Outcome; Vulva

Oral lichen planus is a common, chronic mucosal disease associated with T-cell-mediated immunological dysfunction. The disease is classified in a painful red form with erosions and ulcerations and a less painful to painless white form with reticular, papular and plaque lesions. In a small proportion of cases, the lesions may develop into a squamous cell carcinoma. Corticosteroids are the mainstay of the therapy; the combination of systemic and topical corticosteroids is often very effective. Topical calcineurin inhibitors, especially tacrolimus, have produced long-term responses in clinical studies. We describe a patient with excellent response to therapy with tacrolimus mouthrinse and systemic corticosteroids.

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Clobetasol; Drug Therapy, Combination; Humans; Injections, Intravenous; Lichen Planus, Oral; Male; Middle Aged; Mouth Diseases; Tacrolimus; Treatment Outcome

To investigate the effectiveness of pimecrolimus treatment in patients not responding to corticosteroid treatment and to investigate its effect on Fas expression on keratinocytes in oral lichen planus (OLP).. Twenty patients with OLP were recruited from the Oral Medicine Clinic at the School of Dentistry, Ain Shams University, Egypt. Pimecrolimus 1% cream with a hydrophilic adhesive gel base was applied to the oral lesions, four times daily, for a total of 2 months. A marker lesion was identified and assessed by clinical scoring (CS). The symptomatology score was obtained using a visual analog scale (VAS). Pre-treatment and post-treatment specimens were immunohistochemically stained for detecting Fas.. The results of clinical scores showed statistically high significant improvement (P = 0.0001). The mean VAS decreased significantly over time as well as the mean of Fas expression (P < 0.05). The overall percentage of reduction from baseline to week 8 was 87%, 93%, and 67% for clinical scores, visual analog score, and Fas expression, respectively.. Topical pimecrolimus reduced Fas expression, and it appears to be a promising alternative treatment for OLP.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Apoptosis; Calcineurin Inhibitors; Coloring Agents; fas Receptor; Female; Follow-Up Studies; Gels; Gingival Diseases; Glucocorticoids; Hematoxylin; Humans; Immunosuppressive Agents; Keratinocytes; Lichen Planus, Oral; Male; Middle Aged; Mouth Mucosa; Ointments; Pain Measurement; Tacrolimus; Tongue Diseases; Treatment Outcome; Triamcinolone Acetonide

To evaluate disease dynamics, treatment results, and frequency of malignant transformation. Ten-year single center retrospective study. The study included 171 patients, 28-99 years old. Follow-up was 1-16 years. 49.5% exhibited changes in clinical presentation, with 19% yearly increase of probability for type shift. Index of extent (number of oral locations) showed a mean 40% decrease and 94.1% reported improvement. There were significant differences between treated and untreated patients (P=0.012). Patients with or without systemic diseases had identical treatment requirements for oral lesions. The prevalence of SCC was 5.8%. Oral lichen planus constantly changes presentation and extent of involvement. The effect of systemic diseases was insignificant in the present study. There is a clear value for treatment to reduce the extent of lesions. The results indicate that all clinical forms of the disease need to be equally followed since the clinical presentation typically changes over time, while malignant transformation can occur in all forms.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Clobetasol; Dexamethasone; Female; Humans; Lichen Planus, Oral; Male; Middle Aged; Mouth Neoplasms; Precancerous Conditions; Prednisone; Prevalence; Retrospective Studies; Tacrolimus; Tretinoin; Triamcinolone

Annular atrophic lichen planus is a rare form of lichen planus, clinically characterized by a circumscribed annular configuration. We report herein a 32-year-old female who developed depressed plaques on the lips. Physical examination showed well-circumscribed, erythematous plaques on the lower lip. The border was slightly elevated and the inner portion was depressed and atrophic. Also, a bean-sized well-circumscribed plaque with slightly elevated border was found on the upper lip. A biopsy specimen revealed that the epithelium of the mucous membrane was reduced in thickness and a mononuclear cell infiltration invaded the basement membrane of the epithelium. This is the first case of annular atrophic lichen planus involving the lip. She was treated with 0.1 percent tacrolimus ointment once daily, which resulted in a beneficial effect.

Topics: Adult; CD8-Positive T-Lymphocytes; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Lip Diseases; Ointments; Patch Tests; Tacrolimus; Treatment Outcome; Zinc

Lichen planus (LP), the prototype of lichenoid dermatoses, is an idiopathic inflammatory disease of the skin and mucous membranes, hair follicles, and nails. It rarely occurs on the lips and usually then in association with oral lesions. We report a 40-year-old man with a 3-month history of an isolated single annular violaceous plaque of the lower lip. The rest of his mucosae, skin, hair and nails were normal. Histopathology confirmed the diagnosis of LP. The patient was advised to use topical tacrolimus 0.03 percent cream twice daily along with multivitamins, but the patient was lost to follow-up. Isolated LP of the lip is unusual, although this condition may be underestimated and therefore under-reported in the literature.

Topics: Adult; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Lip Diseases; Lost to Follow-Up; Male; Ointments; Tacrolimus

The role of Toll-like receptors (TLRs) has been elucidated in many human infectious, autoimmune and neoplastic diseases. Previously, TLR2 and TLR4 expression in oral lichen planus (OLP) was described. The aim of our study was to examine expression patterns of TLR4 and TLR9 in normal oral mucosa and OLP and describe the effect of topical tacrolimus treatment on the expression of TLR4 and TLR9 in OLP.. Toll-like receptor 4 and TLR9 expression was analysed by immunohistochemistry in five samples of normal oral mucosa and 50 samples of OLP (31 representing clinically white and 19 clinically erythematous/erosive lesions). We evaluated also the effect of topical tacrolimus on TLR4 and TLR9 expression in a patient with OLP.. Toll-like receptor 4 and TLR9 expression was increased in OLP epithelium compared with normal epithelium (P < 0.001); no significant difference between the two clinical types of OLP was observed. TLR9 expression was strongest in the superficial layer of the epithelium (P < 0.001), while the expression of TLR4 was strongest in the basal layer (P < 0.001). Treatment of OLP lesions with topical tacrolimus resulted in clinical improvement but had no effect on TLR expression levels.. Toll-like receptor 4 and TLR9 are induced in OLP; our finding confirms the results of a previous study. TLR4 and TLR9 may play a part in the pathogenesis of OLP. Further studies are needed to dissect the definitive role of TLRs in OLP pathogenesis and progression and to determine the effect of tacrolimus on the function of TLRs.

Topics: Administration, Topical; Case-Control Studies; Humans; Immunohistochemistry; Immunosuppressive Agents; Lichen Planus, Oral; Mouth Mucosa; Reference Values; Tacrolimus; Toll-Like Receptor 4; Toll-Like Receptor 9

Oral lichen planus (OLP) is a chronic mucosal disorder of unclear etiology. The mainstay of therapy is topical use of steroids but other immuno-modulating therapies have also been tried. One such example is topical application of tacrolimus. Tacrolimus was in 2000 approved for treatment of atopic dermatitis, but in 2005 a boxed warning was included because of a potential risk of cancer development and for lack of long-term studies of the safety of the drug. The present study describes a patient who in 2003 was diagnosed with OLP and where treatment has included an intermittent use of tacrolimus. Five years after diagnosis, the patient developed a squamous cell carcinoma in the region where tacrolimus had been applied. The possible relationship between the use of tacrolimus and cancer development and rationale to include tacrolimus in OLP treatment is discussed.

Topics: Administration, Buccal; Carcinoma, Squamous Cell; Clobetasol; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Mouth Neoplasms; Tacrolimus; Triamcinolone Acetonide

Topics: Aged; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Mouthwashes; Recurrence; Retrospective Studies; Tacrolimus

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Tacrolimus

Topics: Dermatologic Agents; Female; Humans; Lichen Planus, Oral; Middle Aged; Ointments; Tacrolimus

Topics: Clinical Trials as Topic; Humans; Immunosuppressive Agents; International Cooperation; Lichen Planus, Oral; Tacrolimus

Topics: Aged, 80 and over; Calcineurin Inhibitors; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Oral Ulcer; Recurrence; Tacrolimus; Time Factors

Topics: Humans; Lichen Planus, Oral; Pentoxifylline; Recurrence; Stomatitis, Aphthous; Tacrolimus

This clinical report describes the treatment of a patient in need of an immediate complete denture who presented with severe erosive lichen planus. In conjunction with an immediate complete denture, tacrolimus (0.1%) ointment, an immunosuppressive agent, was applied topically over the lesions. There was a significant reduction in the size of the lesions at the second week of treatment, allowing the patient to tolerate the prosthesis without pain, thereby improving her quality of life.

Topics: Administration, Topical; Aged; Contraindications; Denture, Complete, Immediate; Female; Humans; Immunosuppressive Agents; Jaw, Edentulous; Lichen Planus, Oral; Maxilla; Palate; Severity of Illness Index; Tacrolimus; Treatment Outcome

Topics: Administration, Topical; Adult; Cheilitis; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Palliative Care; Salivary Gland Diseases; Tacrolimus

This clinical report describes the treatment of a patient in need of an immediate complete denture who presented with severe erosive lichen planus. In conjunction with an immediate complete denture, tacrolimus (0.1%) ointment, an immunosuppressive agent, was applied topically over the lesions. There was a significant reduction in the size of the lesions at the second week of treatment, allowing the patient to tolerate the prosthesis without pain, thereby improving her quality of life.

Topics: Aged; Denture, Complete, Immediate; Denture, Complete, Upper; Female; Humans; Immunosuppressive Agents; Jaw, Edentulous; Lichen Planus, Oral; Tacrolimus

Oral lichen planus (LP) is a severe, painful form of LP, and is often resistant to topical corticosteroid therapy. Recently, open trials demonstrated that topical tacrolimus therapy was effective for the treatment of chronic erosive oral LP. We report two cases with severe recalcitrant erosive oral LP, who dramatically benefited from topical tacrolimus therapy. In case 1, a 64-year-old man presented with a 5-month history of painful erosions on his entire lower lip and buccal mucosa. Physical and histological examination confirmed a diagnosis of LP. He experienced rapid relief from pain and a dramatic improvement was obtained within 5 weeks of topical tacrolimus treatment. No significant irritation was observed and blood tacrolimus level was kept within a safe level (2.5 ng/mL). In case 2, a 68-year-old man developed painful erosions on his right lower lip and buccal mucosa 2 months before his arrival at our hospital. Histopathological analysis confirmed a diagnosis of oral LP. He experienced a rapid dramatic improvement of both lesions within 4 weeks of the start of tacrolimus application. No significant irritation or recurrence was observed. Thus, topical tacrolimus is suggested as a well-tolerated, effective therapy for oral LP.

Topics: Administration, Topical; Aged; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Recurrence; Tacrolimus

Since tacrolimus ointment was approved by the U.S. Food and Drug Administration (FDA) as a promising treatment for atopic dermatitis, it has been approved in more than 30 additional countries, including numerous European Union member nations. Moreover, in the current clinical routine the use of this drug is no longer restricted to the approved indication, but has been extended to a wide variety of inflammatory skin diseases including some with the potential of malignant transformation. So far, the side-effects reported from the topical use of tacrolimus have been relatively minor (e.g. burning, pruritus, erythema). Recently, however, the FDA reviewed the safety of topical tacrolimus, which resulted in a warning that the use of calcineurin inhibitors may be associated with an increased risk of cancer.. Oral lichen planus (OLP) was diagnosed in a 56-year-old women in February 1999. After several ineffective local and systemic therapeutic measures an off-label treatment of this recalcitrant condition using Tacrolimus 0.1% ointment was initiated in May 2002. After a few weeks of treatment most of the lesions ameliorated, with the exception of the plaques on the sides of the tongue. Nevertheless, the patient became free of symptoms which, however, reoccurred once tacrolimus was weaned, as a consequence treatment was maintained. In April 2005, the plaques on the left side of the tongue appeared increasingly compact and a biopsy specimen confirmed the suspected diagnosis of an oral squamous cell carcinoma.. The suspected causal relationship between topical use of tacrolimus and the development of a squamous cell carcinoma prompted us to test the notion that the carcinogenicity of tacrolimus may go beyond mere immune suppression. To this end, tacrolimus has been shown to have an impact on cancer signalling pathways such as the MAPK and the p53 pathway. In the given case, we were able to demonstrate that these pathways had also been altered subsequent to tacrolimus therapy.

Topics: Administration, Topical; Calcineurin Inhibitors; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Enzyme Activation; Female; Guanine Nucleotide Exchange Factors; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Middle Aged; Mitogen-Activated Protein Kinase 3; Tacrolimus; Tongue Neoplasms; Ubiquitin-Protein Ligases

Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; CD11 Antigens; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Injections, Subcutaneous; Lichen Planus, Oral; Middle Aged; Prednisone; Tacrolimus

Topics: Administration, Topical; Humans; Immunosuppressive Agents; Lichen Planus; Lichen Planus, Oral; Male; Middle Aged; Penile Diseases; Tacrolimus; Thalidomide

The lichen planus is a mucocutaneous disease with unknown etiology and auto-immune pathogenia. There have been three variants of lichen planus: the reticular, the plaque-like and the atrophic-erosive lesions. It s a chronic disease with acute relapses that generally affects more frequently to women from the fourties. The diagnostic is based on the clinic identification of the lesions joined with the histopathologic study (basal cells hidropic degeneration, linfoplasmocitic infiltration and absence of displasy signs). The great number of therapeutic options are explained for its high prevalency (0.5-2%), its recurrence and its risk for malignant transformation. We present a case of oral erosive lichen planus, refractory to numerous treatments, mainly corticosteroids. During 15 days the lesion responded to the administration of a 0.1% tacrolimus in topic application. This article tries to show the new indication of tacrolimus, a calcineurin inhibitor immunosuppressor, that it is effective in the erosive lesions treatment.

Topics: Administration, Topical; Adrenal Cortex Hormones; Aged; Drug Resistance; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Tacrolimus

Topics: Adult; Diagnosis, Differential; Female; Humans; Immunosuppressive Agents; Laser Therapy; Lichen Planus; Lichen Planus, Oral; Nails; Prognosis; Steroids; Tacrolimus; Tongue; Treatment Outcome

Erosive oral lichen planus (OLP) is a painful chronic inflammatory disease that is sometimes resistant to systemic or topical therapies. Topical steroids remain the mainstay of therapy, but topical tacrolimus has recently been used to treat OLP resistant to topical corticosteroids. Topical tacrolimus appears as an effective and safe treatment of symptomatic OLP. We report the first histopathologically documented case of oral mucosa pigmentation after OLP treatment with topical tacrolimus. The relation between tacrolimus treatment and staining was suggested by the appearance of pigmentation during topical tacrolimus treatment and its clinical disappearance when treatment was stopped. Histopathology showed an increase in melanocyte numbers and melanogenesis.

Topics: Administration, Cutaneous; Aged; Diagnosis, Differential; Female; Humans; Hyperpigmentation; Immunosuppressive Agents; Lichen Planus, Oral; Mouth Diseases; Mouth Mucosa; Tacrolimus

Topics: Contraindications; Drug Interactions; Immunosuppressive Agents; Lichen Planus, Oral; Ointments; Tacrolimus

Erosive lichen planus is a painful and disabling disease that is frequently resistant to topical and systemic therapies. Current therapies are considered palliative rather than curative as many patients relapse after discontinuing treatment. An association has been reported between some cases of oral lichen planus (OLP) and chronic hepatitis C infection.. We report on a 51-year-old hepatitis C-positive man with corticosteroid refractory erosive lichen planus of the lip who had a rapid resolution of his lesions following a two-week course of topical 0.1% tacrolimus ointment. The patient remains symptom-free at one year post-treatment.. This case supports the safety and efficacy of topical tacrolimus in patients with steroid-refractory OLP associated with chronic hepatitis C.

Topics: Administration, Topical; Hepatitis C, Chronic; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Mouth Mucosa; Ointments; Tacrolimus; Treatment Outcome

Topics: Administration, Topical; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Middle Aged; Mouth Mucosa; Pigmentation Disorders; Tacrolimus

Topics: Administration, Topical; Adult; Aged; Dermatologic Agents; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Ointments; Tacrolimus; Treatment Outcome

Topics: Aged; Aged, 80 and over; Dermatologic Agents; Female; Humans; Lichen Planus, Oral; Ointments; Tacrolimus; Treatment Outcome

Bone marrow transplantation (BMT) is a common treatment used for deficiencies of host marrow or in the control of blood malignancies. Post-allogeneic BMT complications include graft-versus-host disease (GVHD). GVHD occurs when immunologically active T lymphocytes are transplanted into an immunosuppressed recipient who is genetically disparate from the donor. In this case report we describe the occurrence of oral lichen planus-like lesions as the first manifestation of chronic GVHD (c-GVHD) and the subsequent management of this disease with topical tacrolimus.. Diagnostic aids included routine histology and direct immunofluorescence studies to rule out immunobullous diseases and to confirm the c-GVHD. Treatment consisted of topical application of 0.1% tacrolimus ointment three times a day.. Routine histology confirmed the clinical diagnosis of oral lichen planus-like c-GVHD. Treatment with tacrolimus ointment completely resolved the oral lesions after 2 months of therapy.. Topical tacrolimus at low concentrations (0.1%) shows promise in the management of oral lichen planus-like c-GVHD. Controlled studies are necessary to assess the efficacy, the duration of therapy required for effective results, and the safety of this treatment over the long-term.

Topics: Administration, Topical; Bone Marrow Transplantation; Chronic Disease; Graft vs Host Disease; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Tacrolimus

Erosive oral lichen planus (LP) is a painful chronic inflammatory condition that is frequently resistant to immunosuppressive agents. Topical tacrolimus has been reported as a safe and effective treatment.. To evaluate the efficacy and safety of topical tacrolimus in the treatment of symptomatic erosive oral LP.. A retrospective review of consecutive patients with oral LP treated with topical tacrolimus between June 1999 and November 2003 was performed. Clinical improvement and adverse events were recorded by the physician. Patients were asked retrospectively to rate their symptoms immediately prior to and after tacrolimus therapy using a visual analogue scale.. Physician-observed clinical improvement was found in 21 of 23 patients (91.3%) within 6 weeks. Six patients (26.1%) remained asymptomatic after stopping treatment and 15 patients (65.2%) required maintenance therapy to prevent subsequent flares. Patients' self-reported symptom scores were significantly better (p<0.001) with tacrolimus treatment, which supported physician-observed clinical improvement. There was no evidence of systemic absorption and only minor local side effects were noted.. Topical tacrolimus is an effective treatment for erosive oral LP. The majority of patients require long-term therapy to maintain remission.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Ointments; Retrospective Studies; Tacrolimus

Topical tacrolimus has been reported to be effective for the treatment of oral lichen planus. This article describes our experience with topical tacrolimus in patients treated for symptomatic oral lichen planus.. A survey was mailed to 40 patients with symptomatic oral lichen planus treated with topical tacrolimus. Surveys were completed by 37 patients (93%) a mean of 1.3 years after initiation of treatment. Thirty-three (89%) of the 37 patients reported symptomatic improvement, and 31 (84%) reported partial to complete lesion clearance while using topical tacrolimus. On average, patients noted improvement in 1 month. Twelve patients (32%) reported adverse effects consistent with those reported previously (ie, burning, irritation, and tingling). Among the 28 patients still using the medication, 15 patients (54%) apply it at least once daily. Of the 9 patients who discontinued using the medication, 5 experienced recurrence.. Topical tacrolimus is effective for the treatment of oral lichen planus. Most patients experienced symptomatic improvement in less than 1 month. However, the effect is temporary; when topical tacrolimus is discontinued, oral lichen planus may flare again.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Middle Aged; Recurrence; Surveys and Questionnaires; Tacrolimus; Time Factors; Treatment Outcome

Giving the immunosuppressive drug tacrolimus (FK506) to liver transplant patients has helped to considerably reduce oral side effects such as gingival hyperplasia. Patients taking cyclosporin who suffer from gingival hyperplasia are often switched to tacrolimus.. We present here a pediatric liver transplantation case study. The patient has been followed for 5.5 years. She developed oral lesions that resulted in the immunosuppressive therapy being changed from tacrolimus to cyclosporin. In clinical terms, the atypical pathology consisted of hyperpigmented patches on the gingival margin, the internal surfaces of the cheeks, and the intraoral surfaces of the lips. When located on the lips, the hyperpigmented patches were associated with pruriginous and edematous lesions.. Optical and electronic microscopic examinations of a gingival tissue sample revealed the presence of melanin incontinence and lichenoid lesions with degenerated keratinocytes and a mild infiltrate of lymphocytes. This points to a chronic graft-versus-host disease (cGvHD)-like syndrome linked to tacrolimus. This diagnosis was given further credence by improvement in the lesions following the switch to cyclosporin.. To our knowledge, this is the first reported case of tacrolimus-associated chronic GvHD-like syndrome occurring in the oral mucosa.

Topics: Chronic Disease; Diagnosis, Differential; Female; Gingival Diseases; Graft vs Host Disease; Humans; Immunosuppressive Agents; Infant; Lichen Planus, Oral; Liver Transplantation; Melanosis; Prurigo; Tacrolimus

Oral lichen planus (OLP) is a relatively common, chronic inflammatory condition, which frequently presents with symptoms of pain and irritation. OLP is often difficult to manage. Therefore there is a need for more effective and safer therapies for symptomatic OLP.. Our purpose was to determine the effectiveness of topical tacrolimus as therapy for symptomatic OLP.. A retrospective review was performed of 13 patients with symptomatic OLP treated with topical tacrolimus between September 1999 and September 2000.. Eleven of the 13 patients reported definite symptomatic response to treatment and 2 had no response. Eight patients had a partial response, whereas 3 patients had a complete response with respect to lesion clearance. Seven of the responding patients had no flares with continued treatment. The other 4 patients noted flares soon after stopping the treatment. Side effects were rare and minor.. In this retrospective case series of 13 patients, topical tacrolimus was well tolerated and appeared to be an effective therapy to control symptoms and clear lesions of OLP.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Immunosuppressive Agents; Lichen Planus, Oral; Male; Medical Records; Middle Aged; Retrospective Studies; Tacrolimus; Treatment Outcome

Topics: Age Factors; Aged; Child; Controlled Clinical Trials as Topic; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Infant; Lichen Planus, Oral; Ointments; Tacrolimus; Time Factors