Version May 2024
INTRODUCTION — Oral lichen planus (LP) is a mucosal subtype of LP that presents with a variety of clinical features. Patients may develop reticular oral LP (white papules and plaques), erythematous (atrophic) oral LP (mucosal atrophy and red patches), and/or erosive oral LP (erosions or ulcers) (picture 1A-B). Although reticular oral LP is usually asymptomatic, pain typically accompanies the erythematous and erosive forms of oral LP. The discomfort associated with these last two clinical subtypes is the reason why many patients seek treatment.
The management and prognosis of oral LP will be reviewed here. The diagnosis of oral LP and information on other manifestations of LP are discussed separately. (See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis" and "Lichen planus" and "Vulvar lichen planus" and "Lichen planopilaris" and "Overview of nail disorders", section on 'Lichen planus' and "Lichenoid drug eruption (drug-induced lichen planus)".)
APPROACH TO TREATMENT — Since there is no cure for oral LP, the primary goals of treatment are the alleviation of symptoms and the minimization of scarring and resulting dysfunction from erosive lesions. Patients with asymptomatic reticular oral LP do not require treatment.
Oral LP is managed with a combination of nonpharmacologic and pharmacologic measures, with some variability in the therapeutic approach based upon patient-specific factors (eg, disease extent, tolerance to treatment, comorbid disease) and treatment availability. In general, local therapy is preferred over systemic therapy to minimize the potential risk of serious adverse effects related to treatment.
Topical corticosteroids are the first-line local treatment; additional options for local therapy include topical calcineurin inhibitors and intralesional corticosteroid injections. In our experience, most patients have at least a partial response to local therapy. A lack of improvement should prompt an evaluation for potential contributors, such as candidal infection, reactivation of oral herpes simplex virus (HSV), misdiagnosis, nonadherence to therapeutic regimen, and intolerability to the therapeutic formulation. Additionally, a biopsy may be indicated to rule out malignant transformation for any lesion that fails to improve with site-directed treatment.
Systemic therapy should be reserved for patients who fail to respond sufficiently to local therapy or for patients who have both oral LP and extraoral involvement.
An important component of patient management is the recognition and treatment of ocular, laryngeal, esophageal, and/or vulvovaginal/penile LP. Patients with signs or symptoms suggestive of such involvement should be referred to an appropriate specialist (ophthalmologist, otolaryngologist, gastroenterologist, gynecologist, or urologist/urogynecologist) for further evaluation and the coordination of care. (See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis", section on 'Extraoral findings'.)
The role of direct-acting antiviral therapy for hepatitis C virus (HCV) 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 [1-4]. (See "Overview of the management of chronic hepatitis C virus infection", section on 'Antiviral therapy'.)
NONPHARMACOLOGIC MEASURES — Several nonpharmacologic measures may help to reduce morbidity associated with oral LP. Exposure to factors that may exacerbate the disease should be minimized. We typically encourage the following:
●Maintenance of good oral hygiene (brushing twice daily, flossing daily, professional dental cleaning every three to four months)
●Elimination 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)
●Cessation of smoking or use of smokeless tobacco
●Reduced consumption of acidic, salty, spicy, hot, sharp, or rough foods
Patients with oral LP may find maintenance of oral hygiene challenging due to the discomfort elicited during oral care. However, the accumulation of dental plaque and calculus may cause local irritation and exacerbation of oral LP (Koebner phenomenon) [5,6]. Patients with significant gingival involvement are prone to periodontal disease [7]. (See "Overview of gingivitis and periodontitis in adults".)
We instruct patients to brush their teeth twice daily with a soft bristle toothbrush and bland toothpaste (ie, unflavored or at least devoid of mint or cinnamon flavoring). Use of a sonic toothbrush 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 [8].
Patients should be instructed to floss once daily with unflavored dental floss or tape. Professional dental cleanings should be performed every three to four months.
FIRST-LINE THERAPY
Topical corticosteroids — Topical corticosteroids are the first-line treatment for oral LP [9-13]. High-potency or medium-potency topical corticosteroids (potency groups 1 to 3) are typically used (table 1) [9,14-19].
Efficacy — The efficacy of topical corticosteroids for oral LP was evaluated in a small placebo-controlled randomized trial. In the nine-week trial, 40 patients with reticular and/or erosive oral LP were treated with either a group 3 potency topical corticosteroid (a 0.025% concentration of fluocinonide in an adhesive base) or placebo. Both substances were applied at least six times per day [16]. Among the 20 patients treated with fluocinonide, 4 (20 percent) had complete responses, and 12 (60 percent) had good or partial responses to therapy. In contrast, no complete responses and only six partial responses (30 percent) occurred in the placebo-treated patients.
Beneficial effects of treatment with topical corticosteroids have also been reported in several randomized trials that have compared individual corticosteroid therapies [14,17-20]. A systematic review of randomized trials that evaluated the efficacy of treatments for reducing pain due to oral LP found insufficient evidence to conclude superiority of any specific topical corticosteroid therapy [10,21].
Limited data suggest that a 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 [22].
Administration — We usually prescribe a high-potency topical corticosteroid, such as clobetasol propionate 0.05%, fluocinonide 0.05%, or betamethasone dipropionate 0.05% gel or ointment, and instruct patients to dry the affected areas (with gauze) prior to application. The topical corticosteroid is applied four to six times per day using a fingertip or cotton-tipped applicator (eg, Q-tip). Eating, drinking, and even speaking should be avoided for at least 30 minutes after application. As symptoms improve, the frequency of application is reduced as tolerated.
In our experience, at least partial improvement is typically evident within one month of consistent treatment. We typically treat for at least two months prior to concluding ineffectiveness of topical corticosteroid therapy.
Gingival trays may facilitate treatment for patients with significant gingival involvement (picture 2) [23]. 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) are an option for patients with widespread oral disease and patients who have difficulty applying topical corticosteroids to the affected areas [24].
Topical corticosteroids have also been formulated in adhesive dental bases with the intent of augmenting the response to treatment. However, superior efficacy of these formulations is not proven [25,26].
Side effects — Oropharyngeal candidiasis is a common side effect of intraoral topical corticosteroid use and can be prevented or treated with antifungal therapy [9,27]. In a small, randomized trial, the addition of prophylactic miconazole to clobetasol therapy did not affect the efficacy of oral LP treatment and was associated with a lower rate of oropharyngeal candidiasis [27]. (See "Esophageal candidiasis in adults" and "Oropharyngeal candidiasis in adults".)
We monitor patients closely for symptoms and signs of candidiasis and perform confirmatory testing (usually with a potassium hydroxide [KOH] preparation) when the diagnosis is suggested. If a fungal culture is performed, the results should be carefully correlated with the clinical presentation since oral colonization with Candida species is common [28].
To minimize the risk of oral candidiasis, patients with dental appliances should remove them overnight. In addition, appliances should be soaked twice daily for 20 minutes in dilute (0.02%) sodium hypochlorite solution, 0.12% chlorhexidine gluconate, or nystatin suspension (100,000 units/mL) [24].
Systemic absorption of intraoral topical corticosteroids may be related to the extent of erosive disease, pharmacologic characteristics of the corticosteroid (ie, potency), and/or patient utilization practices (ie, quantity, frequency of use). A pilot study of triamcinolone acetonide 0.1% in the treatment of 20 patients with oral LP demonstrated no systemic absorption over four weeks of use [29]. However, systemic absorption of intraoral topical corticosteroids has been documented [30] and may rarely result in systemic adverse effects, including adrenal suppression [31]. The risk for adrenal suppression in patients treated for oral LP appears to be low [32]. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)
SECOND-LINE THERAPY — Treatment options for patients who fail to respond to topical corticosteroids or who cannot tolerate topical corticosteroid therapy (eg, allergic contact mucositis, recurrent oropharyngeal candidiasis) include topical calcineurin inhibitors (pimecrolimus, tacrolimus, and cyclosporine) and intralesional corticosteroids. A disadvantage of topical calcineurin inhibitors is the typically higher cost in comparison with topical corticosteroids. Intralesional corticosteroid injection can be painful, may require multiple office visits, and has little available data on treatment efficacy.
Topical pimecrolimus and tacrolimus — The topical calcineurin inhibitors pimecrolimus and tacrolimus are effective for oral LP [33,34]. Randomized trials comparing the efficacy of these agents with topical corticosteroids indicate that pimecrolimus 1% can be at least as effective as triamcinolone 0.1% [35] and tacrolimus 0.1% can be at least as effective as clobetasol 0.05% [36-38]. Pimecrolimus has not been directly compared with clobetasol or any other superpotent topical corticosteroid (table 1). A systematic review of randomized trials failed to find conclusive evidence of superiority of either topical calcineurin inhibitors or topical corticosteroids for reducing pain due to oral LP [10,21].
Efficacy — Efficacy data on topical pimecrolimus and topical tacrolimus are reviewed below:
●Pimecrolimus – The efficacy of pimecrolimus in oral LP is supported by small, randomized, placebo-controlled trials [39-41]. In a randomized trial in which 20 adults with erosive oral LP were treated with either pimecrolimus 1% 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. In addition, a significantly greater reduction in the disease severity score was detected in the treatment group. The three patients who had not responded to pimecrolimus at the 30-day time point all achieved major improvement after an additional 30 days of treatment.
The efficacy of four times daily application of pimecrolimus 1% cream and triamcinolone acetonide 0.1% paste were compared in a separate randomized trial of 40 patients with oral LP [35]. The two treatments had similar efficacy at two months.
●Tacrolimus – The efficacy of topical tacrolimus is evident in randomized trials that have compared treatment with tacrolimus 0.1% ointment to clobetasol 0.05% ointment [36-38]. Based upon these trials, tacrolimus appears to be at least as effective as clobetasol. The trials are reviewed in greater detail below:
•In a randomized trial in which 32 patients described as having moderate to severe oral LP were treated with application of either tacrolimus or clobetasol four times per day for four weeks, statistically significant reductions in disease symptoms and signs occurred in both groups [36]. However, median scores for pain, burning sensation, and mucosal lesion extension at the end of therapy were significantly lower in the tacrolimus group.
•In a randomized trial of 30 patients with erosive LP treated with tacrolimus or clobetasol four times per day for two weeks, followed by a progressive taper to one time per day over a total of six weeks, the efficacy of the two agents was similar [37]. Twenty-nine patients were analyzed, and all but one patient who had received clobetasol responded to treatment. The differences in the percent reduction in lesion size at week six (83 percent for tacrolimus and 82 percent for clobetasol) and the percent reduction in pain score at week six (52 percent for tacrolimus and 38 percent for clobetasol) were not statistically significant.
•In a randomized trial in which 40 patients with symptomatic oral LP were treated with twice-daily application of tacrolimus or clobetasol for eight weeks, statistically significant reductions in the net clinical score were seen in both groups, and the score reductions were not significantly different between the groups [38]. In addition, the differences in the rates of complete response (70 versus 40 percent, respectively) and complete or partial response (95 versus 90 percent, respectively) were not statistically significant between the tacrolimus and clobetasol groups.
Administration — We administer topical pimecrolimus and topical tacrolimus in a similar manner as topical corticosteroids, instructing patients to apply medication to the affected areas after drying the sites with gauze. Treatment is applied two to four times daily [33], and patients should avoid eating and drinking for at least 30 minutes after application. The frequency of application is tapered as tolerated.
Pimecrolimus is commercially available as a 1% cream. Tacrolimus is commercially available as both a 0.03% and 0.1% ointment; the literature supports the use of the 0.1% concentration [33].
Side effects — Burning sensation may occur after application of topical calcineurin inhibitors [33]. Tacrolimus has been detected in the blood of patients treated with topical tacrolimus for oral LP, indicating that systemic absorption occurs [42].
Concerns have been raised regarding the potential for pimecrolimus and tacrolimus to increase the risk for cancer, evidenced by the US Food and Drug Administration's placement of a "black box" warning on these agents. However, a causative relationship between these agents and cancer has not been demonstrated to date and remains controversial. (See "Treatment of atopic dermatitis (eczema)".)
Intralesional corticosteroids — Intralesional injections of triamcinolone acetonide, in concentrations between 10 and 40 mg/mL, have been used successfully for oral LP. A study of 45 patients with ulcerative oral LP on the bilateral buccal mucosa in which only one side was treated with an intralesional corticosteroid injection (0.5 mL of triamcinolone acetonide 40 mg/mL) found statistically significant reductions in signs and symptoms of oral LP within two weeks after treatment [43]. On the treated side, the mean sizes of the areas affected by erythema or ulceration were reduced by 78 percent. In contrast, the untreated areas remained unchanged.
In our experience, intralesional injection using triamcinolone acetonide (5 to 10 mg/mL) has been effective. Using 30-gauge one-half inch-length needles, we inject into the submucosa of recalcitrant oral LP lesions. Injections may be repeated every two to four weeks as needed [43-45].
Intralesional injection of betamethasone, a more potent corticosteroid than triamcinolone acetonide, may be an effective 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), significantly more patients in the betamethasone group compared with the triamcinolone acetonide group achieved healing (27 of 29 [93 percent] versus 20 of 30 [67 percent]) [46]. Additional study will be useful for confirming the relative efficacy of these treatments.
Side effects related to systemic absorption are risks of intralesional corticosteroid therapy [45]. (See "Intralesional corticosteroid injection", section on 'Adverse effects and pitfalls'.)
Topical cyclosporine — Studies have yielded variable results regarding the efficacy of topical cyclosporine in oral LP [15,47,48]. A small placebo-controlled randomized trial in which 16 patients with symptomatic oral LP used topical cyclosporine (5 mL of a 100 mg/mL solution, swished for five minutes and then spit) or its vehicle three times daily supported the use of topical cyclosporine for this indication [47]. After eight weeks, clinical improvement in erythema, erosions, reticulation, and pain were significantly greater in the treatment group than in the placebo group. All eight patients treated with cyclosporine had marked clinical improvement, whereas the eight 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 [48]. There was no significant difference between the two groups in efficacy.
SEVERE AND REFRACTORY DISEASE — Oral LP that cannot be adequately managed with topical therapy or extensive oral LP accompanied by extraoral mucosal involvement may require more aggressive treatment with systemic glucocorticoids. Less commonly, other systemic immunomodulatory agents are used for treatment. Data on the efficacy of systemic agents are primarily limited to small uncontrolled studies, case reports, and case series. The potential for serious drug-induced adverse effects is a concern for these therapies.
Oral glucocorticoids — Oral glucocorticoids have appeared to be effective for oral LP in small uncontrolled studies [49,50]. 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 [49].
We typically treat patients with prednisone at a dose similar to the dose above, with the goal of tapering to discontinuation within two to four weeks to minimize the risk for drug-related adverse effects. Because relapses frequently occur after the discontinuation of oral glucocorticoids, we use topical corticosteroids to sustain improvement during tapering and after the cessation of systemic therapy. (See 'Topical corticosteroids' above.)
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 or clobetasol without systemic therapy [51]. Significant differences in patient outcomes were not detected.
The adverse effects of systemic glucocorticoids are reviewed separately. (See "Major adverse effects of systemic glucocorticoids".)
Other systemic immunomodulatory agents — Additional agents that may be useful in patients with severe or refractory oral LP based upon data from case reports and small, retrospective studies include immunosuppressants, such as azathioprine (50 mg twice daily) [50,52,53], cyclosporine (5 mg/kg per day) [54], methotrexate (2.5 to 15 mg per week) [55,56], mycophenolate mofetil (1 to 2 g per day) [57-59], oral tacrolimus (0.5 to 1 mg twice daily) [60], and thalidomide (50 to 200 mg per day) [55,61-63]. The role of rituximab in oral LP is unclear, with both new-onset disease and improvement noted in case reports [64,65]. Data for the use of apremilast in oral LP are preliminary but promising [66]. We await larger, controlled clinical trials that assess the efficacy of various biologic agents in the treatment of oral LP [67].
ADDITIONAL THERAPIES — Other therapies that have been reported to be effective for oral LP include topical retinoids [68,69], oral retinoids [70-74], hydroxychloroquine [55,75], topical rapamycin [76], oral dapsone (100 to 150 mg per day) [77,78], and oral metronidazole [79]. 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 [80].
Treatment of oral LP with a variety of ultraviolet light-based modalities has been attempted [81]. 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 [82-86]. Whether ultraviolet light therapy increases the risk for malignant transformation to oral squamous cell carcinoma, 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.)
Additional physical interventions for oral LP have included surgery [81], photodynamic therapy [87,88], carbon dioxide lasers [89,90], and cryotherapy [44,91].
PAIN MANAGEMENT — Nonsteroidal anti-inflammatory agents or acetaminophen may be added for pain management. In our experience, few oral LP patients 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 [92]. 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 [93,94]. Patients who are experiencing these symptoms may benefit from referrals to psychological 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 [95]. 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 Italian 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 [44].
Risk of oral squamous cell carcinoma — The magnitude of the risk of malignant transformation of oral LP to oral squamous cell carcinoma (SCC) is unclear [96]. 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 [44,97-99]. The highest risk for oral SCC may occur in patients with longstanding, erythematous or erosive oral LP [100,101].
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 study is 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 [102]. 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 — We follow all patients with oral LP at least every 6 to 12 months, which allows for the assessment for early signs of malignancy. In addition to the oral exam, 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 an 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
●Oral lichen planus (LP) is a subtype of LP that presents with reticular, erythematous (atrophic), or erosive lesions on the oral mucosa. Although reticular oral LP is often asymptomatic, patients with the erythematous and erosive subtypes of oral LP usually have associated pain. (See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis", section on 'Clinical subtypes'.)
●Treatment of oral LP is implemented to improve symptoms and to minimize the risk for scarring and resulting dysfunction from erosive lesions. Patients with asymptomatic reticular LP do not require treatment. (See 'Approach to treatment' above.)
●For patients with symptomatic oral LP, we suggest treatment with a high-potency topical corticosteroid (eg, clobetasol propionate 0.05% or betamethasone dipropionate 0.05%) as first-line therapy (Grade 2B). (See 'First-line therapy' above.)
●For patients who fail to improve adequately with topical corticosteroids or who cannot tolerate topical corticosteroids, we suggest treatment with tacrolimus 0.1% ointment or pimecrolimus 1% cream (Grade 2B). Additional options for these patients include topical cyclosporine and intralesional corticosteroid injections. (See 'Second-line therapy' above.)
●Patients who do not respond adequately to local therapy may benefit from treatment with oral glucocorticoids or other systemic immunomodulatory therapies. (See 'Severe and refractory disease' above.)
●Oral LP is a risk factor for oral squamous cell carcinoma, though the magnitude of this risk remains unclear. A biopsy should be performed if patients develop lesions suspicious for oral malignancy. (See 'Risk of oral squamous cell carcinoma' above.)
●Patients with oral LP should be followed clinically at least every 6 to 12 months. More frequent follow-up may be indicated based upon 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.
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