For Students & Dentists: The Management Of Oral Lichen Planus

Oral lichen planus is an immune-mediated and chronic inflammatory condition that can cause erosion of the oral mucosa. The disease is described as reticular, erosive, atrophic, or bullous in nature, and it typically develops in women in their fifth and sixth decades. Reticular oral lichen planus, absent erythema, is asymptomatic and does not usually need intervention. However, as there is potential for conversion to carcinoma, reticular oral lichen planus associated with erythema or erosion needs treatment and periodic re-evaluation. The literature suggests that erosive and ulcerated oral lichen planus is best managed with topical corticosteroid preparations and, in refractory cases, systemic steroids. Several other immunosuppressive medications and non-medication based interventions are also available, but at greater cost and with greater potential for adverse reactions and side effects. This educational review article focuses on best practices in the management of oral lichen planus.

Factors/conditions reported in mucosal lichen planus development:

  1. Genetics
  2. Infection
  3. Lichenoid drug reaction
  4. Vitamin/mineral deficiencies
  5. Systemic disease
  6. Amalgam hypersensitivity

Reticular LP

Reticular LP is typically asymptomatic and does not routinely require intervention. However, due to the white striations and plaques associated with reticular LP and their similar appearance to oral cancer, all lesions should be documented in the patient chart, including recording of the location(s), taking photographs, and other pertinent descriptions of the lesions. In addition, lesions associated with reticular LP should be monitored for changes, such as size, thickness, coloration of mucosa, ulceration or erosion, and emergent symptoms such as pain, that may be indicative of potential dysplastic conversion.

Dysplastic transformation of lichen planus is relatively rare, as is evidenced by a systematic review of over 7,000 subjects with LP where malignant transformation was reported in only 3.7% of cases.

Transformation to malignancy is reported to occur more frequently in female patients, with the tongue serving as the most common site of expression. If transformation to a premalignant lesion (dysplasia) is suspected, histopathologic evaluation is indicated.

In patients with lichenoid lesions caused by hypersensitivity to amalgam or other restorative materials, or those with lesions that suggest a lichenoid drug reaction, treatment consists of removal of the associated restoration(s) or discontinuation of the offending medication under the guidance of the patient’s physician. The following medications are associated with lichenoid drug reactions: antihypertensives, including beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and diuretics; antibiotics, such as penicillin, aminosalicylate sodium, isoniazid rifampin, streptomycin, and tetracyclines; non-steroidal anti-inflammatories (NSAIDs); oral hypoglycemic agents; antiretroviral medications; antimalarials, such as hydroxychloroquine; anticonvulsants, such as carbamazepine, oxacarbazepine, phenytoin, valproate; antidiarrheals, such as bismuth; antifungals, such as amphotericin B and ketoconazole; and antihistamines, such as cimetidine, cinnarizine, and triprolidine.

Lichenoid reactions tend to be widespread over the mucosa, while lesions associated with dental restorative material will be confined to mucosa that is in close contact with the material. At present, there appears to be little reason to remove all amalgam restorations in patients with generalized reticular lichen planus.

Erosive/Ulcerative Lichen Planus

Similar to other forms of lichen planus, erosive/ulcerative lichen planus (ELP) is a chronic disease with no known cure. Regardless of therapy, complete resolution of lesions is difficult to achieve. Future research may identify cellular and genetic mechanisms that prove useful in the development of effective long-term treatment strategies and a possible cure. Until that time, the clinician treating ELP must utilize either pharmacotherapy known to suppress immune function and pain and promote healing or non-pharmacological interventions that have previously shown promise in managing the disease. Most medication strategies used to treat ELP have limited supportive evidence, as few of these are supported by studies using rigorous scientific methodology. There is even less evidence-based support for non-pharmacological interventions such as photochemotherapy, photodynamic therapy, or laser therapy, which have also been suggested as treatment for ELP.

erosive-lp

Topical corticosteroids continue to be widely utilized as a first-line therapy for erosive/ulcerative LP in both medicine and dentistry. Additionally, high-potency topical steroids are thought to be the most effective strategy for reducing symptoms and minimizing disease in patients with severe pathology. One example of this is a double-blind placebo-controlled clinical study where a 75% improvement was reported following the application of fluocinonide in an adhesive base. High-potency topical treatments include clobetasol (Temovate®), fluocinonide (Lidex®), and halobetasol (Ultravate®), all three of which are dispensed as 0.05% creams or ointments. Clobetasol propionate and fluocinonide are also provided in a 0.05% solution, but the FDA has recommended that these products only be used externally because of the possibility of hypothalamuspituitary-adrenal inhibition. Gels can be mixed with equal parts orabase to make an adhesive paste for application to small- or medium-sized lesions.

It is recommended that lesions should be coated with the gel or cream after each meal and at bedtime. Broader coverage can sometimes be achieved through the use of an acrylic appliance that holds the gel or cream against the mucosa. Dexamethasone, another potent corticosteroid, is effective in treating generalized erosive or ulcerative lesions. It is prescribed as a rinse that is held in the mouth for a short time. When used three or four times daily, maximum coverage is provided.

Two prescriptions are presented:

Rx: Dexamethasone (Decadron) elixir 0.5mg/5ml (Disp 320 mls; Sig [1] For 3 days, rinse with 1 tablespoonful (15ml) qid and swallow. Then [2], for 3 days, rinse with 1 teaspoonful (5ml) qid and swallow. Then [3], for 3 days, rinse with 1 teaspoonful (5ml) qid and swallow every other time. Then [4], rinse with 1 teaspoonful (5ml) qid and expectorate).

Another prescription is: Rx: Dexamethasone elixir 0.5mg/5ml (Disp 100mls; Sig: Rinse with 1 teaspoonful (5ml) for 3-4 minutes qid and spit out); discontinue when lesions become asymptomatic.

Either approach may be considered reasonable intervention as published research comparing these two prescriptions of dexamethasone is not available. Even with topical application of corticosteroid to mucosa, there is potential for systemic, as well as local side effects. Close collaboration with the patient’s physician is recommended, particularly when these medications are prescribed for a prolonged period of time. Systemic prednisone can also be prescribed, but its use should be considered only in cases involving severe recalcitrant lesions where topical approaches to therapy have failed. If systemic corticosteroid is considered, it should be prescribed at the lowest possible dosage and only for a short time. There are a number of prescribing regimens that are effective such as: Rx: Prednisone tablets 5mg (Disp: 40 tabs; Sig: Take 5 tablets in the morning for five days, then 5 tablets in the morning every other day until gone.) Medrol dose packs are also available. Any patient using corticosteroids should be monitored for the emergence of fungal infection (candidiasis), that can occur with application of this class of drugs. If the LP patient is prone to fungal infections or has experienced candida infection in the past following steroid administration, prophylactic antifungal therapy should be pursued as concurrent therapy.

Additional immunosuppressant medications and immunomodulatory agents that may be considered to manage severe recalcitrant erosive/ulcerative LP include calcineurin inhibitors such as cyclosporine, tacrolimus, and pimecrolimus. However, these drugs are expensive and there are few studies supporting the use of cyclosporine. Further, local and systemic side effects can be problematic. Pimecrolimus and tacrolimus, indicated for the treatment of atopic dermatitis, have a number of studies supporting their use in treating LP. These drugs inhibit T-cell activation and cytokine release from mast cells. Systematic review of five double blind studies and ten prospective studies, as well as numerous case reports, suggest that topical tacrolimus ointment 1% may be equal to topical clobetasol propionate 0.05% ointment and topical triamcinolone acetonide 0.1% paste, in terms of treatment outcome. Treatment with topical tacrolimus appears to result in measurable blood levels but, according to Swift et al., this medication has not been associated with significant adverse effects. However, prolonged use of tacrolimus may increase cancer risk, and therefore, should only be applied for a short period of time. The FDA recommends against oral application of this medication to mucosa. Other medications, such as retinoids, dapsone, azathioprine, mycophenolate mofetil, acitretin, and enoxaparin, that have been recommended for use with ELP have limited scientific support and should not be routinely utilized. The use, particularly long term, of some of the aforementioned drugs may result in adverse reactions. For example, two common side effects of dapsone use are hemolysis and hypersensitivity reactions in the form of fever and jaundice, typically occuring within the first six weeks of therapy. Finally, all of the abovementioned drugs are more expensive relative to the cost of corticosteroids.

Non-pharmacological Treatment Modalities

There are several non-pharmacological interventions suggested for treatment of ELP. These include PUVA therapy, where uses are application of the sensitizing drug psoralen followed by ultraviolet light; photodynamic therapy, which includes a photosensitizer, light source, and tissue oxygen; and laser therapy. Only the latter is likely to be utilized in the dental office. These strategies have limited supportive evidence for treating LP but might be considered for severe recalcitrant cases. When 21 atrophic/erosive LP patients who were treated with laser phototherapy (LPT) three times a week for three months were compared to 21 atrophic/erosive LP patients who used clobetasol propionate 0.05% applied three times a day for three months.  The LPT group was found to have a higher percentage of complete lesion resolution at 60 and 90 days with no recurrence of lesions. In contrast, the clobetasol group was reported to have experienced worsening of all the variables analyzed. Although this suggests that LPT may be quite effective in the treatment of recalcitrant ELP, an in-office application three times a week might be difficult for some patients to manage. PUVA therapy has been associated with adverse events, including nausea, dizziness, and 24-hour photosensitivity. Although not considered “treatment,” patients with LP should be advised to maintain good oral hygiene and instruction in appropriate care should be considered to reduce injury to involved tissues. Dietary recommendations should include instructions to eat soft nutritious food during outbreaks, the avoidance of caffeine, and cessation of smoking and alcohol. Since ELP may be aggravated by stress and can be associated with depression, activities that reduce stress and modify depression should be suggested. Another novel approach to treatment that has not been extensively studied but may be useful is antioxidant application (e.g., AO ProVantageGel). In one case study, the gel was applied three times daily for eight weeks with symptom improvement continuing for over a year. There is also published evidence that the saliva of a patient with LP exhibits increased levels of oxidative stress and lower antioxidant capacity compared to the saliva of healthy patients.

Conclusion

Dental professionals are likely to encounter one or more cases of LP during clinical practice. Since it is probable that they will encounter reticular LP, the importance for the clinician to differentiate between this disease and other more serious problems, such as dysplasia, is high. However, it is the erosive/ulcerative LP that will require direct clinical intervention and careful monitoring. This course has presented several pharmacologic approaches to treatment that are evidence-based or common practice for managing erosive/ulcerative LP. In addition, the course provided suggestions for non-pharmacologic interventions, which may have limited use. Although a number of new drugs have been suggested for the treatment of ELP, at the present time, topical application of corticosteroid medication followed by systemic administration in severe refractory cases remains the standard of care.

Reference: This article was written by Kimberly M. Parsons, EdD, CDA, EFDA, RDH.

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