Version July 2025
INTRODUCTION —
Oral lichen planus (LP) is a mucosal subtype of LP that presents with a variety of clinical features. Clinical subtypes include reticular oral LP (white striations, papules, and plaques), erythematous (atrophic) oral LP (mucosal atrophy and red patches), and erosive oral LP (erosions or ulcers) (picture 1A-B).
Oral LP typically has a chronic and recurrent course. The primary goal of treatment is to reduce the pain and morbidity typically associated with erythematous and erosive disease.
The management and prognosis of oral LP, including the association with risk for oral squamous cell carcinoma (SCC), will be reviewed here. The clinical features and diagnosis of oral LP are discussed separately.
●(See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis".)
Other manifestations of LP are also discussed separately.
●(See "Lichen planus".)
●(See "Vulvar lichen planus".)
●(See "Lichenoid drug eruption (drug-induced lichen planus)".)
●(See "Overview of nail disorders", section on 'Lichen planus'.)
APPROACH TO MANAGEMENT —
There is no curative treatment for oral LP. The primary goals of treatment are to alleviate symptoms and minimize the scarring and functional impairment that result from erosive lesions. The clinical presentation influences the approach to treatment (algorithm 1A-B).
Reticular disease — Isolated reticular oral LP is typically asymptomatic (picture 2). In general, we do not treat asymptomatic reticular oral LP. However, we advise periodic clinical follow-up. (See 'Follow-up' below and "Oral lichen planus: Pathogenesis, clinical features, and diagnosis", section on 'Clinical subtypes'.)
Our approach to asymptomatic reticular oral LP is based on the knowledge that patients are not bothered by reticular oral LP and that benefit of treatment for reducing progression to symptomatic oral LP has not been proven.
Symptomatic reticular oral LP is uncommon and often represents the coexistence of reticular oral LP with erythematous oral LP (picture 3). Our approach to the management of symptomatic reticular disease resembles our approach to the treatment of erythematous or erosive oral LP. (See 'Erythematous and erosive oral lichen planus' below and "Oral lichen planus: Pathogenesis, clinical features, and diagnosis", section on 'Clinical subtypes'.)
Erythematous, erosive, or symptomatic disease — Erythematous, erosive, and/or otherwise symptomatic oral LP is managed with a combination of nonpharmacologic and pharmacologic measures (picture 1B-D). (See 'Erythematous and erosive oral lichen planus' below.)
Our approach generally consists of:
●Treatment with topical or systemic immunomodulatory drugs
●Guidance regarding oral hygiene
●Trigger avoidance
In addition, patients with erythematous or erosive LP may have an increased risk for oral squamous cell carcinoma (SCC). Close clinical follow-up is indicated to support optimal disease control and early detection of signs of SCC. (See 'Prognosis and follow-up' below.)
Extraoral disease — Oral LP may occur in conjunction with LP involving other body areas. Early recognition and appropriate treatment of LP in sites at greatest risk for morbidity, scarring, and functional disability is important. Examples of extraoral mucosal sites include ocular, otic, laryngeal, esophageal, vulvovaginal, and penile involvement.
Patients with signs and/or symptoms suggestive of such involvement should be referred to and managed in conjunction with an appropriate specialist (ophthalmologist, otolaryngologist, gastroenterologist, gynecologist, or urologist/urogynecologist). Dermatologists play an important role in coordinating specialist care. (See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis", section on 'Extraoral findings'.)
ERYTHEMATOUS AND EROSIVE ORAL LICHEN PLANUS
Initial management — Our initial approach to erythematous and erosive oral LP typically consists of topical corticosteroid therapy, oral hygiene measures, and trigger avoidance. In general, local pharmacologic therapy is preferred over systemic therapy to minimize the risk of serious adverse effects. Systemic therapy is generally reserved for disease refractory to topical therapy, severe disease, and scenarios in which concomitant high-risk extraoral LP (eg, ocular, otic, laryngeal, esophageal, vulvovaginal, or penile involvement) requires systemic therapy (algorithm 1A-B). (See 'Severe or refractory disease' below and 'Extraoral disease' above.)
Topical corticosteroids — Topical corticosteroids are our preferred initial pharmacologic treatment for oral LP (algorithm 1A).
Administration — Initial topical corticosteroid therapy for oral LP involves the application of a high-potency topical corticosteroid (potency groups 1 to 2) to the affected areas up to six times per day (usually four times per day) (table 1) [1-8].
We typically prescribe clobetasol propionate 0.05%, fluocinonide 0.05%, or betamethasone dipropionate 0.05% in a gel or ointment vehicle. We prefer gel and ointment vehicles over creams or pastes because of improved ease of application and tolerability. Creams can leave a poor taste in the mouth, and pastes may leave a gritty sensation.
We reassure patients that topical corticosteroid ointments and gels may be used on the oral mucosa despite the labels or package inserts, which often caution against internal use.
In our experience, clinical improvement typically becomes evident within one month of consistent treatment. If marked improvement has not occurred after two months of high-potency corticosteroid therapy, we stop the corticosteroid and proceed to other treatments. (See 'Insufficient response to topical corticosteroids' below.)
●Application technique – An application technique that supports adequate contact of topical therapy to the affected mucosa is an important aspect of treatment. We typically instruct patients to:
•Dry the affected area with gauze.
•Apply the topical corticosteroid using a fingertip or cotton swab (eg, Q-tip).
•Avoid eating, drinking, and speaking for at least 30 minutes after application. (The site of application may also be covered with a nonstick pad during the 30-minute period to provide occlusion. Application with occlusion may be particularly helpful for focal buccal mucosal or gingival lesions.)
●Tapering of therapy – As symptoms improve, the frequency of high-potency corticosteroid application is reduced to two times per day, then to once daily, and then to every other day as tolerated for symptom management. For erosive lesions, tapering should not begin until erosions have healed.
Once disease control is maintained with a high-potency topical corticosteroid applied every other day, the potency can be reduced. We typically proceed to a medium-potency topical corticosteroid. Subsequently, we continue to taper the potency and the frequency of application as tolerated.
●Alternative application methods – Alternative techniques that may improve treatment application or treatment tolerability include the use of gingival trays or corticosteroids in elixir, suspension, or adhesive dental base formulations.
•Gingival tray – Gingival trays help to retain topical therapy in the target area and may facilitate treatment for patients with extensive gingival involvement (picture 4) [9]. The patient adds the topical corticosteroid to the tray in areas corresponding to the areas of gingival disease, places the tray in the mouth, and leaves it in place for 10 to 20 minutes. Patients repeat treatment two to four times per day.
•Elixir or suspension vehicle – Oral elixirs or suspensions (eg, 5 mL of dexamethasone [0.5 mg/5 mL] used as a mouth rinse up to six times per day) may facilitate treatment for patients with widespread oral disease and patients who have difficulty applying topical corticosteroids to the affected areas [10]. To allow for sufficient contact time, patients should swish for three to five minutes before expectorating (spitting).
•Adhesive dental bases and patches – Topical corticosteroids have been formulated in adhesive dental bases with the intent of augmenting the response to treatment. However, greater efficacy of these formulations has not been proven, and pastes may leave a gritty sensation or residue that limits compliance [11,12].
Small randomized trials suggest efficacy of some investigational drug delivery systems in oral LP. Examples include a clobetasol-impregnated mucoadhesive patch and dexamethasone in a mucoadhesive polymer gel [13,14].
Efficacy — Although randomized trials suggest a benefit of corticosteroids for oral LP, comprehensive assessment of the available data is complicated by limitations, such as small trial sizes and wide variability in trial treatment regimens and outcome assessment measures [8].
Examples of trials include:
●In a prospective trial, 32 patients with painful lesions of oral LP were randomly assigned to twice-daily treatment with either clobetasol propionate 0.05% mixed with a 4% hydroxyethyl cellulose gel or the 4% hydroxyethyl cellulose gel alone for eight weeks [15]. All patients treated with clobetasol propionate reported symptom improvement compared with 50 percent of patients in the vehicle-only group. The difference in the rate of resolution for all atrophic-erosive lesions was not statistically significant between the groups (87.5 percent of patients treated with clobetasol and 62.5 percent of patients treated with vehicle achieved resolution).
●In a prospective trial, 40 patients with reticular and/or erosive oral LP were randomly assigned to at least six times daily use of either fluocinonide 0.025% in an adhesive ointment base or a placebo ointment for nine weeks [4]. Patients treated with fluocinonide were more likely to achieve a response. Improvement on photographic assessment rated as more than 67 percent improvement, 34 to 66 percent improvement, or 1 to 33 percent improvement occurred in 20, 45, and 15 percent of patients in the fluocinonide group, respectively. Similar outcomes occurred in only 0, 20, and 10 percent of patients in the placebo group, respectively. Symptom improvement was also more common in the fluocinonide group.
High-quality trials are necessary to clarify the effects of topical corticosteroids and other therapies in oral LP [8]. A meta-analysis of data from the trials described above supported benefit of topical clobetasol and fluocinonide for pain resolution (risk ratio [RR] 1.91, 95% CI 1.08-3.36, I2 = 0) compared with placebo but did not confirm benefit for achieving clinical resolution (RR 6.00, 95% CI 0.76-47.58, I2 = 0) [8].
Beneficial effects of treatment with topical corticosteroids have also been reported in randomized trials that have compared individual topical corticosteroid therapies [2,5-7,16,17]. Although some trials suggest a greater benefit of particular formulations, such as a trial that found faster efficacy of three-times daily gargling with a betamethasone 0.137 mg/mL mouthwash for reducing the areas of erosive and atrophic lesions and pain compared with a dexamethasone 0.181 mg/mL mouthwash [17], data are insufficient for conclusions about the comparative efficacy of different topical corticosteroid therapies [8].
Limited data suggest that findings from the pretreatment biopsy may be helpful for predicting the response to topical corticosteroid treatment. In a study of 100 patients with oral LP, the presence of plasma cells was associated with better responses to topical corticosteroid treatment [18,19].
Adverse effects
●Secondary oropharyngeal candidiasis – Secondary oropharyngeal candidiasis is a common side effect of intraoral topical corticosteroid use. (See "Oropharyngeal candidiasis in adults".)
•Diagnosis – We monitor patients closely for symptoms and signs of secondary oropharyngeal candidiasis. Common symptoms include a dry or cottony sensation of the mouth and/or worsening burning sensations of the oral mucosa despite more frequent use of topical corticosteroids. Thick or foamy saliva may also be seen. (See "Oropharyngeal candidiasis in adults".)
Oropharyngeal candidiasis may present as the classic pseudomembranous presentation but more often presents as erythematous candidiasis, which can look identical to erythematous LP. Empiric treatment is often appropriate for patients with supportive signs or symptoms of secondary Candida infection. Confirmatory tests include a potassium hydroxide (KOH) preparation (for suspected pseudomembranous oral candidiasis) or fungal culture. (See "Oropharyngeal candidiasis in adults", section on 'Diagnosis'.)
•Treatment – Oral candidiasis is treated with topical or oral antifungal therapy. Our typical approach consists of nystatin rinses, clotrimazole troches (lozenges), or oral fluconazole. (See "Oropharyngeal candidiasis in adults", section on 'Treatment'.)
•Prophylaxis – For patients who experience recurrent episodes of secondary candidiasis during topical corticosteroid therapy, we typically prescribe prophylactic anti-Candida therapy [1,20]. Our typical prophylactic regimen is fluconazole at 200 mg weekly or 100 mg twice weekly, provided drug interactions with fluconazole are not a concern. Alternative approaches include clotrimazole troches (lozenges) two to three times per day and other prophylactic regimens. (See "Oropharyngeal candidiasis in adults", section on 'Patients with recurrent disease'.)
Patients with removable dental appliances who experience recurrent episodes of secondary candidiasis during topical corticosteroid therapy may benefit from measures that may reduce the risk for reinfection. The acrylic pores in dental appliances can act as a reservoir for Candida. Thus, we instruct patients to remove dental appliances overnight and to soak the appliances twice daily for 20 minutes in dilute (0.02%) sodium hypochlorite solution (1 teaspoon/cup water) or nystatin suspension (at a dose of 100,000 units/mL) [10]. Chlorhexidine gluconate has also been used for disinfection but is associated with risk of teeth discoloration.
●Other adverse effects – Adrenal suppression related to systemic absorption is a potential risk of topical corticosteroid therapy [21]. However, limited data suggest that adrenal suppression due to topical corticosteroid therapy for oral LP is rare [22,23].
Mucosal atrophy from topical corticosteroids appears uncommon, possibly due to salivary dilution. Atrophy of facial gingivae and interdental papillae is difficult to distinguish from oral LP disease activity. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)
Oral hygiene — Maintenance of oral hygiene can be challenging due to the discomfort elicited during daily oral care and routine dental cleanings.
However, maintenance of oral hygiene is critical. The accumulation of dental plaque and calculus may cause local irritation and exacerbation of oral LP [24,25]. In addition, patients with significant gingival involvement are prone to periodontal disease [26]. (See "Overview of gingivitis and periodontitis in adults".)
Hygiene techniques and products that may cause excessive trauma or local irritation should be avoided because of the potential for disease exacerbation. In general, we advise:
●Twice-daily toothbrushing with a soft bristle toothbrush and bland toothpaste (ie, unflavored or at least devoid of mint or cinnamon flavoring and sodium lauryl sulfate)
●Once-daily flossing with unflavored dental floss, tape, or water flosser
●Professional dental cleanings every three to four months
Use of a sonic toothbrush on low settings may provide effective cleaning while minimizing discomfort and tissue trauma. In addition, colorimetric plaque indicators may facilitate the identification of plaque that should be removed during brushing [27,28].
Trigger avoidance — Clinical experience suggests that trigger identification and avoidance may be a helpful adjunctive therapeutic strategy. In one questionnaire-based study (n = 51) in which 94 percent of patients identified at least one factor that sometimes or always caused flares of oral LP, the majority of patients who said they actively avoided triggers reported improvement in symptoms and/or reduced flare frequency [29].
Examples of commonly reported triggers for oral LP include stress; acidic, spicy, and crunchy foods; oral hygiene products; dental procedures; and alcohol [29,30]. (See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis", section on 'Inciting factors'.)
We typically advise:
●Avoidance of mechanical irritation from dental restorations, dental appliances, or sharp or malaligned teeth
●Avoidance of habits that cause trauma (eg, chewing on lips or mucosa)
●Avoidance of smoking and smokeless tobacco use
●Reduced consumption of acidic (citrus fruits, vinegar-based sauces), salty, spicy, hot, sharp, or rough/crunchy foods
●Initiation of interventions to reduce stress or anxiety
Additional study is necessary to clarify the effects of trigger avoidance in oral LP.
Insufficient response to topical corticosteroids
Patient assessment — In our experience, most patients have a partial response or excellent response to topical corticosteroid therapy. A lack of improvement should prompt an evaluation for potential contributors, such as Candida infection, reactivation of oral herpes simplex virus (HSV) infection, misdiagnosis, insufficient adherence to the therapeutic regimen, and intolerability to the therapeutic formulation.
Additionally, a biopsy is indicated to rule out malignant transformation for persistent ulcers or erosions that fail to improve with treatment [31]. (See 'Risk of oral squamous cell carcinoma' below.)
Selection of subsequent therapy — When oral LP responds insufficiently to topical corticosteroid therapy or topical corticosteroid therapy is poorly tolerated (eg, allergic contact mucositis, recurrent secondary oropharyngeal candidiasis), we usually proceed to a trial of another local therapy, such as a topical calcineurin inhibitor for more widespread disease or intralesional corticosteroid therapy for more focal disease (particularly of the buccal mucosae, tongue, or other "loose" tissues) (algorithm 1A). (See 'Topical calcineurin inhibitors' below and 'Intralesional corticosteroid injections' below.)
Although topical calcineurin inhibitors and intralesional corticosteroid injections are considered effective for oral LP, certain factors contribute to our use of these agents as subsequent therapy rather than initial therapy. Disadvantages of topical calcineurin inhibitors are the typically higher cost compared with topical corticosteroids and the frequent side effect of burning on application. Intralesional corticosteroid injection can be painful, may require multiple office visits for repeat treatment, and has limited data on treatment efficacy.
Topical calcineurin inhibitors — Topical tacrolimus 0.1% ointment and topical pimecrolimus 1% cream are the topical calcineurin inhibitors typically used for oral LP. Topical cyclosporine solution is an alternative calcineurin inhibitor but requires compounding, has been less extensively studied than tacrolimus, and has not been proven more effective than tacrolimus or pimecrolimus [32-34].
Calcineurin inhibitors act as immunomodulators by binding to intracytoplasmic proteins in T lymphocytes (cyclosporine to cyclophilin, tacrolimus and pimecrolimus to FK506-binding protein). The binding inhibits calcineurin and induces suppression of transcription and production of variable cytokines.
●Administration – Tacrolimus is commercially available as both a 0.03% and 0.1% ointment. The 0.1% ointment is our preferred formulation for oral LP because efficacy data for tacrolimus 0.03% ointment are more limited [32,35]. Pimecrolimus is available as a 1% cream.
We prefer topical tacrolimus over pimecrolimus because of the ointment vehicle. Our experience suggests that ointment vehicles provide greater ease of application and better patient tolerance compared with cream vehicles. (See 'Topical corticosteroids' above.)
Our application regimen for pimecrolimus and tacrolimus is similar to our regimen for topical corticosteroid therapy. Two to four times per day, patients apply the medication to the affected areas after drying the sites with gauze [36]. Patients should avoid eating and drinking for at least 30 minutes after application. The frequency of application is tapered as tolerated.
As with topical corticosteroids, applying topical calcineurin inhibitor using a gingival tray is an alternative. (See 'Topical corticosteroids' above.)
In clinical practice, compounded tacrolimus rinse (eg, 1 mg of tacrolimus per 500 mg of water) has also been used as a swish and spit. A small randomized trial suggests benefit of an investigational tacrolimus 0.1% mucoadhesive patch for oral LP [37].
Similar to topical corticosteroids, responses to topical calcineurin inhibitors are typically evident within one month. If there is a clinical response, the frequency of application can be progressively tapered from four times per day, to two times per day, once per day, and to every other day and less frequent use as tolerated. If there is no clinical response after two months, we proceed to other treatments.
●Efficacy – The topical calcineurin inhibitors are considered effective for oral LP based on data from small randomized trials that support efficacy [32]. However, most trials have been small and have methodologic and outcome assessment differences, contributing to uncertainty about the relative efficacy of topical calcineurin inhibitors compared with topical corticosteroids [8,32].
•Tacrolimus – Trials assessing the efficacy of topical tacrolimus for oral LP have primarily involved comparisons with topical corticosteroids and generally suggest benefit for oral LP [8,32].
In a meta-analysis of two randomized trials (n = 52) that compared clinical resolution outcomes after treatment with tacrolimus with outcomes after treatment with clobetasol, clobetasol appeared less effective for clinical resolution (RR 0.61, 95% CI 0.38-0.99) [8]. Based on a meta-analysis of two randomized trials (n = 100), clobetasol also appeared less effective than tacrolimus for pain resolution (RR 0.45, 95% CI 0.24-0.88) [8]. However, the very low certainty of this evidence due to factors such as small trial size, risk of bias, and high heterogeneity warrants cautious interpretation of these outcomes.
A meta-analysis of data from two randomized trials that compared tacrolimus with triamcinolone (n = 60) did not find statistically significant differences in clinical resolution [8].
•Pimecrolimus – The efficacy of pimecrolimus in oral LP is supported by small randomized trials [38-40]. In one trial in which 20 adults with erosive oral LP were randomly assigned to treatment with either pimecrolimus 1% cream or a vehicle cream twice daily for 30 days, 7 of 10 patients in the pimecrolimus group achieved complete clearance or marked improvement of lesions compared with only 2 of 10 patients in the vehicle group [39]. In addition, the reduction in the disease severity score was greater in the pimecrolimus group. All three patients who had not responded to pimecrolimus at 30 days achieved improvement after an additional 30 days of treatment.
In a separate oral LP trial (n = 40), patients treated with pimecrolimus 1% cream and patients treated with triamcinolone acetonide 0.1% paste four times daily had similar improvement in pain, lesion size and severity, and quality of life at two months [41].
•Topical cyclosporine – Small randomized trials have yielded variable results regarding the efficacy of topical cyclosporine in oral LP [3,33,42,43]. One eight-week trial (n = 16) compared outcomes for symptomatic oral LP from cyclosporine (5 mL of a 100 mg/mL solution, swished for five minutes and then spit) with outcomes from the vehicle alone. All eight patients treated with cyclosporine had marked clinical improvement in erythema, erosion, reticulation, and pain, whereas all patients in the vehicle group had no improvement or minimal benefit.
In contrast, a randomized trial that compared cyclosporine given in a similar swish and spit regimen with triamcinolone acetonide 1 mg/g paste found that both treatments resulted in only slight clinical improvement [42]. There was no significant difference between the two groups in efficacy.
●Adverse effects – A transient burning sensation often occurs after application of topical calcineurin inhibitors [36,37]. Unlike topical corticosteroids, topical calcineurin inhibitors do not appear to increase risk for secondary oropharyngeal candidiasis.
Although laboratory evidence of systemic absorption of topical calcineurin inhibitors can be detected in some patients, treatment is generally well tolerated [32,44]. In a systematic review of randomized trials assessing topical calcineurin inhibitor therapy for oral LP, no serious adverse events were reported [32].
A US Food and Drug Administration (FDA) "boxed" warning was placed on topical tacrolimus and pimecrolimus based on concern for increased risk for cancer. However, a causative relationship between these agents and cancer has not been proven. (See "Treatment of atopic dermatitis (eczema)", section on 'Topical calcineurin inhibitors'.)
Intralesional corticosteroid injections — Intralesional corticosteroid injections are an alternative method of local corticosteroid therapy. Limited data suggest benefit for oral LP.
●Administration – Administration involves injection of a corticosteroid suspension (usually triamcinolone acetonide) directly into the affected areas. Concentrations of triamcinolone acetonide used for oral LP vary, ranging from 10 to 40 mg/mL [31,45]. In our experience, intralesional injection using triamcinolone acetonide (5 to 10 mg/mL) has appeared effective for erosive oral LP.
We typically inject the corticosteroid into the submucosa with a 30-gauge, one-half inch needle and inject 0.2 to 0.3 mL/cm2. No antiseptic is needed prior to injection.
Injections may be repeated every two to four weeks as needed [46-48]. To minimize risk of adverse effects, we aim to administer no more than 40 mg of triamcinolone acetonide per month.
We expect a reduction in symptoms, erythema, or ulcer size after one or two treatments. If there is no improvement in ulcer size after two or three treatments, we proceed to other therapies. (See "Intralesional corticosteroid injection", section on 'Systemic adverse effects'.)
●Efficacy – Efficacy data for intralesional corticosteroid injection for oral LP are limited.
In one study of 45 patients with ulcerative oral LP on the bilateral buccal mucosa, the mucosa on one side only was injected with 0.5 mL of triamcinolone acetonide 40 mg/mL [47]. Reductions in signs and symptoms of oral LP occurred within two weeks after corticosteroid treatment. The mean size of the areas affected by erythema or ulceration decreased by 78 percent in the treated areas, but a statistically significant change was not detected in the untreated areas.
Intralesional injection of betamethasone, a more potent corticosteroid than triamcinolone acetonide, may be an alternative treatment. In a trial in which 61 patients with erosive oral LP were randomly assigned to intralesional injection of 1.4 mg of betamethasone or 8 mg of triamcinolone acetonide (each given once weekly for two weeks), more patients in the betamethasone group achieved healing compared with patients in the triamcinolone acetonide group (27 of 29 [93 percent] versus 20 of 30 [67 percent]) [49]. Additional studies will be useful for confirming the relative efficacy of these treatments.
●Adverse effects – Adverse effects related to systemic absorption are risks of intralesional corticosteroid therapy [48]. Secondary oropharyngeal candidiasis and atrophy are not typically seen. (See "Intralesional corticosteroid injection", section on 'Adverse effects and pitfalls'.)
SEVERE OR REFRACTORY DISEASE —
Oral LP that cannot be adequately managed with topical therapy or extensive oral LP accompanied by extraoral mucosal involvement (particularly pharyngeal or esophageal involvement) may require systemic treatment. For example, systemic therapy is often necessary for patients with multiple areas of erosive disease and severe pain that limits the ability to maintain adequate oral intake.
We typically start with oral glucocorticoids (algorithm 1B). We tend to incorporate other drugs when patients require frequent repeated courses of systemic corticosteroids to maintain adequate disease control. (See 'Systemic glucocorticoids' below and 'Periodic systemic glucocorticoid therapy insufficient' below.)
Systemic glucocorticoids — Although oral glucocorticoids may be useful for patients with resistant disease, most patients with oral LP do not require an oral glucocorticoid as initial therapy. This concept is supported by a study in which 49 adults with oral LP were treated with either a prednisone taper followed by clobetasol ointment or clobetasol ointment without systemic therapy [50]. Significant differences in patient outcomes were not detected.
●Administration – We typically prescribe prednisone at a dose of 0.5 to 1 mg/kg per day, with the goal of tapering to discontinuation within three to four weeks to minimize the risk for adverse effects. In our experience, improvement may be evident within two weeks, with most patients exhibiting significant improvement by four weeks.
Because relapses frequently occur after stopping treatment with prednisone, we typically use a topical corticosteroid or topical calcineurin inhibitor concurrently with prednisone to sustain improvement during tapering and after the cessation of oral prednisone therapy. When such local therapy is insufficient for sustaining improvement or multiple courses of oral corticosteroids are needed, long-term treatment with other systemic immunomodulatory therapies may be beneficial. (See 'Periodic systemic glucocorticoid therapy insufficient' below.)
●Efficacy – Oral prednisone has appeared effective for oral LP in small uncontrolled studies [51,52]. In one open-label study, 7 of 10 patients with oral LP who were treated with prednisone (40 to 80 mg once daily or 1 mg/kg/day) achieved complete remission within 26 days [51].
●Adverse effects – Oral glucocorticoid therapy is associated with risk for a wide variety of adverse effects. The adverse effects are reviewed in detail separately. (See "Major adverse effects of systemic glucocorticoids".)
Periodic systemic glucocorticoid therapy insufficient
Our approach — We primarily use other systemic therapies when oral LP cannot be adequately controlled with topical therapy and periodic short courses of systemic glucocorticoid therapy or when these treatments are poorly tolerated (algorithm 1B). We aim to avoid long-term treatment with systemic corticosteroids because of the adverse effects associated with long-term therapy. (See "Major adverse effects of systemic glucocorticoids".)
Oral metronidazole is our preferred glucocorticoid-sparing systemic treatment given its relatively favorable side effect profile and relatively quick onset of action. Hydroxychloroquine also has a favorable side effect profile and is often our next choice when metronidazole is poorly tolerated or ineffective.
Oral acitretin and conventional immunosuppressants are options for disease that cannot be successfully treated with metronidazole or hydroxychloroquine. (See 'Oral metronidazole' below and 'Hydroxychloroquine' below and 'Retinoids and conventional immunosuppressants' below.)
Oral metronidazole — Small retrospective studies suggest benefit of metronidazole at doses of 250 mg three times daily or 500 mg twice daily [53-55]. We typically prescribe 500 mg twice daily.
The onset of action may be earlier than other systemic treatment options. Signs of efficacy typically occur around four to six weeks after starting treatment. We treat patients for three months prior to concluding inefficacy.
In one study of 30 patients with oral LP treated with metronidazole 500 mg twice daily, there was an overall response rate of 60 percent (including 33 percent with complete remission) [55]. Side effects were present in 20 percent of patients and were most commonly gastrointestinal in nature, including gastrointestinal distress and dysgeusia. Neuropathy is another potential adverse effect but is often reversible upon metronidazole discontinuation [56].
The mechanism of action of metronidazole in oral LP is unclear but may impact the disease process via changes to the microbiome or anti-inflammatory properties.
Hydroxychloroquine — Hydroxychloroquine is typically given at a dose of 5 mg/kg of actual body weight (maximum dose 400 mg per day). In general, doses should not exceed 5 mg/kg per day because of risk for retinal toxicity. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Dosing'.)
Onset of action is typically between three to six months.
In a trial in which 99 patients with oral LP were randomly assigned to either hydroxychloroquine or dexamethasone 0.05%, patients in both groups achieved similar levels of clinical improvement after four weeks [57]. In small case series, overall response rates have ranged from 70 to 100 percent.
Hydroxychloroquine has a favorable safety profile with minor gastrointestinal side effects and rare long-term side effects, including retinal toxicity [58-62]. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Adverse effects'.)
Retinoids and conventional immunosuppressants — Additional treatment options for severe refractory disease include oral retinoids, methotrexate, azathioprine, and mycophenolate mofetil. Compared with oral metronidazole and hydroxychloroquine, these therapies have less favorable adverse effect profiles and require laboratory monitoring.
●Systemic retinoids – Small studies of systemic retinoids have shown efficacy in the treatment of oral LP [58,63-67].
In a retrospective study that included 17 patients with oral LP treated with isotretinoin 80 mg/day or acitretin 25 mg/day, the overall response rate was 65 percent (18 percent with moderate improvement and 47 percent with substantial improvement) [58].
In the United States, acitretin is often preferred for individuals of nonchildbearing potential because isotretinoin therapy requires participation in a Risk Evaluation and Mitigation Strategy (REMS) program. (See "Oral isotretinoin therapy for acne vulgaris", section on 'iPLEDGE program'.)
Side effects include laboratory abnormalities (including hepatotoxicity and dyslipidemia), teratogenicity xerosis, and cheilitis, among others, which limit use.
●Methotrexate – Methotrexate has been associated with improvement in oral LP at doses ranging from 2.5 to 20 mg once weekly [58,68].
In a retrospective review of 18 patients with erosive oral LP, 33 percent showed moderate improvement and 56 percent showed substantial improvement for an overall response rate of 89 percent [58]. In another retrospective study of 18 patients, 83 percent of patients showed at least partial response at 12 weeks [69].
Broader use is limited by drug-induced immunosuppression and side effects of gastrointestinal issues and hepatotoxicity.
Oral ulceration is a potential adverse effect that can be difficult to distinguish from active erosive or ulcerative oral LP. However, oral ulcerations due to methotrexate are typically associated with other evidence of methotrexate toxicity, such as abnormalities in blood counts or liver function. (See "Major adverse effects of low-dose methotrexate".)
●Azathioprine – Improvement with azathioprine has been reported [52,70,71]. In a prospective study of nine patients with oral LP, seven had an excellent response to azathioprine 100 mg/day for three to seven months [70]. Side effects include immunosuppression, bone marrow suppression, hepatotoxicity, and gastrointestinal distress (most commonly). (See "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Adverse effects'.)
●Mycophenolate mofetil – Improvement with mycophenolate mofetil has been reported [72-74]. In a retrospective study of 10 patients with severe ulcerative oral LP treated with mycophenolate mofetil, total daily doses of 1.5 to 2.5 g per day appeared effective [72]. Adverse effects include immunosuppression and leukopenia, among others. (See "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases", section on 'Adverse effects'.)
Additional and emerging therapies — Responses of oral LP to other therapies have been reported.
●Thalidomide – Thalidomide at doses of 50 to 100 mg per day has shown response rates in oral LP ranging from 83 to 100 percent, with complete response rates of up to 67 percent in small studies of five to six patients each [58,75-77]. Side effects include teratogenicity and neurotoxicity. Relapse upon discontinuation is common.
●Tacrolimus and cyclosporine – Other less commonly used systemic treatments include tacrolimus (at a dose of 0.5 to 1 mg twice daily) [78] and cyclosporine (at a dose of 5 mg/kg per day) [79].
●Apremilast – Case reports and case series suggest benefit of oral apremilast [80,81]. In a retrospective study of 11 patients with oral LP, six patients showed improvement [82]. Apremilast may also be of benefit in esophageal disease [82,83].
●Janus kinase (JAK) inhibitors – JAK inhibitors may be a novel treatment option for oral LP. Case reports and small case series suggest efficacy in patients with recalcitrant oral and esophageal disease [84-87].
●Rituximab – In case reports, rituximab has been associated with new-onset oral LP as well as improvement in oral LP [88,89]. It is unclear how rituximab would exert an effect given that it is a B cell-depleting agent, and oral LP is predominantly a T cell-mediated disorder.
●Dupilumab – Similar to rituximab, dupilumab has been reported to induce LP but has also been reported to help cutaneous LP in case reports [90-92].
●Other pharmacologic therapies – Examples of other therapies reported to improve oral LP include topical retinoids [93-95], topical rapamycin [96], a mycophenolate mucoadhesive patch [97], and oral dapsone [98,99].
●Phototherapy – Treatment of oral LP with a variety of ultraviolet (UV) light-based modalities has been attempted [100]. Small uncontrolled studies and case reports have documented improvement in patients treated with psoralen plus ultraviolet A (PUVA) therapy, a 308 nm ultraviolet B (UVB) excimer laser, UVB phototherapy administered via a flexible fiber, and extracorporeal photochemotherapy [101-105].
Whether UV light therapy increases the risk for malignant transformation to oral squamous cell carcinoma (SCC), independent of the underlying risk inherent to oral LP, is unknown. Further study of the efficacy and safety of these interventions is necessary before these treatments can be routinely recommended. (See 'Risk of oral squamous cell carcinoma' below.)
●Procedural therapy – Additional physical interventions for oral LP have included surgery [100], photodynamic therapy [106,107], carbon dioxide (CO2) lasers [108,109], cryotherapy [46,110], and low-intensity laser therapy [111].
●Alternative therapies – Many alternative treatments of oral LP have been suggested as beneficial, including aloe vera [112], hyaluronic acid [113], and lycopene [114].
In a small randomized trial, oral curcuminoids, components of the root turmeric (Curcuma longa), reduced symptoms and signs of oral LP to a greater extent than placebo [115].
●Hepatitis C virus therapy – The role of direct-acting antiviral therapy for hepatitis C virus infection in the setting of oral LP is unclear. In addition to improvement and resolution, worsening and new development of oral LP following the initiation of direct-acting antiviral therapy have been documented in case reports or small case series [116-119]. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Antiviral therapy'.)
PAIN MANAGEMENT —
Nonsteroidal anti-inflammatory agents or acetaminophen may be added for pain management. In our experience, few patients with oral LP have required more aggressive pain medication regimens.
Local pain control with use of intraoral topical anesthetics (viscous lidocaine 2% solution, lidocaine 2% gel) can provide temporary benefit and improved oral intake. Potential risks include systemic absorption with potential toxicity and suppression of gag reflex with increased risk of aspiration.
Topical benzocaine is not advised due to a rare risk of potentially fatal methemoglobinemia with even one application [120]. The risk appears to be greatest in young children. (See "Methemoglobinemia".)
PATIENT SUPPORT —
Oral LP and concomitant chronic pain may be associated with increased risk for anxiety and depression [121,122]. Patients who are experiencing these symptoms may benefit from referrals to psychologic or psychiatric health services for help with coping skills and psychosocial support.
Stress appears to alter a variety of endocrine and immune responses in patients with LP [123]. Further study is necessary to determine whether stress is an exacerbating factor for oral LP.
PROGNOSIS AND FOLLOW-UP —
The clinical course of oral LP is chronic, with waxing and waning severity. In a retrospective study of 808 patients with oral LP who were followed for 6 to 304 months, sustained remission off-therapy was documented in only 2.5 percent of patients [46].
Risk of oral squamous cell carcinoma
●Risk – The magnitude of the risk of malignant transformation of oral LP to oral squamous cell carcinoma (SCC) is unclear [124]. Systematic interpretation of the available data is compromised by marked variability in study inclusion criteria. Reported rates for malignant transformation range from 0.4 to more than 5 percent [46,125-128]. In a systematic review of systematic reviews, the risk of oral SCC developing in oral LP was estimated at 0.44 to 2.28 percent [129].
The highest risk for oral SCC may occur in patients with longstanding erythematous or erosive oral LP [129-131]. Thus, treatment of erythematous or erosive disease is often initiated in hopes of reducing the risk of oral SCC; however, no data are available to validate a reduction of risk for oral SCC with treatment. Isolated reticular oral LP has not been linked to oral SCC.
Field cancerization may play a role as 11 percent of patients with oral LP and a history of oral SCC have multiple oral SCCs [132]. Treatment options for oral LP in these patients is limited given the desire to avoid immunosuppression in the setting of oral SCC. Thus, in a patient with oral LP with a history of intraoral SCC, immunosuppressive medications such as methotrexate, azathioprine, and mycophenolate should be avoided due to increased risk of SCC recurrence and secondary intraoral SCC.
●Interventions – Due to the possibility that oral LP may increase risk for oral cancer, we encourage patients with oral LP to avoid activities known to increase the risk for oral cancer, such as alcohol, areca (betel) nut, and tobacco (smoked and smokeless) use. Additional studies are necessary to determine the impact of these factors and oral human papillomavirus infection on risk for malignant transformation of oral LP.
Future studies also may offer clarity on whether analysis for genetic alterations, such as determination of MYC status, in lesional oral LP tissue will be useful for identifying patients at risk for progression to oral SCC [133]. It is not known whether treatment of oral LP influences the risk of malignancy. (See "Epidemiology and risk factors for head and neck cancer", section on 'Risk factors'.)
Follow-up — Patients with asymptomatic reticular disease who are not receiving treatment should still be monitored yearly by an oral health care clinician. The goal is to assess for changes in disease manifestations or symptoms that necessitate treatment.
We follow all patients with symptomatic oral LP at least every 6 to 12 months, which allows for the assessment of treatment efficacy and for early signs of malignancy. For patients on systemic therapy, the follow-up frequency is typically every three months depending on the frequency of laboratory monitoring needed.
In addition to the oral examination, we palpate cervical lymph nodes to evaluate patients for the presence of lymphadenopathy. A biopsy to rule out oral cancer should be performed if signs suggestive of oral cancer are detected (eg, leukoplakia, exophytic nodules, or persistent ulcers or erosions that fail to respond to therapy).
The need for more frequent follow-up for disease management is dependent on disease activity, symptomatology, and therapeutic regimen.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lichen planus".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Lichen planus (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Disease overview – Oral lichen planus (LP) is a subtype of LP that presents with reticular, erythematous (atrophic), or erosive lesions on the oral mucosa. Reticular oral LP is often asymptomatic. Erythematous oral LP and erosive oral LP are usually painful. (See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis", section on 'Clinical subtypes'.)
●Indications for treatment – Treatment of oral LP is implemented to improve symptoms and to minimize the risk for scarring and resulting dysfunction from erosive or painful lesions. Asymptomatic reticular LP does not require treatment. (See 'Approach to management' above.)
●Approach to treatment – Our initial management of erythematous, erosive, or otherwise symptomatic oral LP involves pharmacologic treatment, counseling regarding oral hygiene, and trigger avoidance. Overall, efficacy data for interventions for oral LP are limited. (See 'Erythematous and erosive oral lichen planus' above.)
•Initial treatment – For patients with symptomatic oral LP, we suggest initial treatment with a high-potency topical corticosteroid (eg, clobetasol propionate 0.05% or betamethasone dipropionate 0.05%) rather than other therapies (algorithm 1A and table 1) (Grade 2C). (See 'Topical corticosteroids' above.)
Topical tacrolimus ointment and intralesional corticosteroid therapy are reasonable alternatives, but we typically reserve these therapies for patients who respond insufficiently to or cannot tolerate topical corticosteroids. Topical tacrolimus is generally higher in cost than topical corticosteroids. Intralesional corticosteroid injections are painful, require office visits, and have limited evidence for efficacy. (See 'Insufficient response to topical corticosteroids' above.)
•Severe or refractory disease – For severe oral LP that cannot be managed with topical or intralesional therapy alone, we suggest a short course of an oral glucocorticoid rather than other systemic therapies (algorithm 1B) (Grade 2C).
We typically treat with prednisone for two to four weeks and sustain clinical improvement with topical therapy. When sustained disease control cannot be attained with this regimen, we incorporate other systemic immunomodulatory therapies, such as oral metronidazole. (See 'Severe or refractory disease' above.)
●Prognosis – The clinical course of oral LP is chronic, with waxing and waning severity.
•Association with squamous cell carcinoma – Oral LP is a risk factor for oral squamous cell carcinoma (SCC). The magnitude of this risk and the effects of treatment of oral LP on risk for SCC are unclear. A biopsy is indicated for lesions with features suspicious for oral malignancy (eg, leukoplakia, exophytic nodules, or persistent ulcers or erosions that fail to respond to therapy). (See 'Risk of oral squamous cell carcinoma' above.)
●Follow-up – Patients with oral LP require long-term clinical follow-up. More frequent follow-up may be indicated based on disease activity, symptomatology, and therapeutic regimen. (See 'Follow-up' above.)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Bethanee J Schlosser, MD, PhD, who contributed to an earlier version of this topic review.
