Continuing Education Activity

Oral lichen planus (OLP) is a chronic T-cell mediated inflammatory disease that affects the oral mucosa. It is characterized by periods of symptomatic exacerbation and remission, and treatment targets reducing inflammation and providing symptomatic relief. This activity reviews the evaluation and management of oral lichen planus and explains the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Summarize the pathophysiology of oral lichen planus.
• Describe the clinical and histologic diagnostic criteria for oral lichen planus.
• Review the management strategies and key patient education points for oral lichen planus.
• Explain the importance and clinical relevance of long-term clinical follow-up.

Introduction

Lichen planus is a chronic inflammatory disease that affects the skin, hair follicles, nails, and mucosa.[1] Mucosal surfaces affected include the oral, genital, ocular, otic, esophageal surfaces, and in rarer instances, the bladder, nasal, laryngeal, and anal surfaces. The skin and oral mucosa are the major sites that are affected.[1][2] 

The oral variant, termed oral lichen planus (OLP), is a chronic condition with periods of relapses and remissions, requiring long-term symptomatic treatment and surveillance monitoring. About 15% of patients with oral lichen planus (OLP) develop cutaneous lesions, and 20% develop genital lesions.[3] 

Cutaneous involvement is usually self-limiting and characterized by violaceous, pruritic papules with overlying reticular white striae, known as Wickam striae. Lesions most commonly appear on the trunk or extremities, such as the wrists and ankles. [4] 

Genital involvement in females demonstrates erythema, erosion, white reticulated plaques, agglutination, resorption of the labia, or scarring.[5] Males may demonstrate annular, papulosquamous lesions on the glans penis. Associated symptoms may include dysuria and dyspareunia.[6] 

More than a quarter of OLP patients also display oesophageal involvement, with symptomatic patients complaining of dysphagia and odynophagia. An endoscopic examination may reveal friable mucosa, white plaques, erythema, ulceration, erosions, and stricture formation.[7][8][9]

Etiology

Oral lichen planus is a known T-cell mediated chronic inflammatory response affecting the oral mucosa. Evidence suggests that other factors such as trauma, dental plaque, and stress may play a role in exacerbating OLP symptoms.[10][11] 

Studies have also demonstrated that in certain geographic locations such as Japan, the Mediterranean region, and the United States metropolitan population, there is a strong association between Hepatitis C virus infection and OLP.[12][13][14]

Epidemiology

The estimated global prevalence of oral lichen planus is about 2%.[15][16] It is twice as common in women and is often diagnosed between the fifth and sixth decades of life, although it may also occur in children and young adults.[17][18][19]

Pathophysiology

While the pathophysiology of oral lichen planus is not entirely understood, the two main proposed mechanisms are antigen-specific and non-specific mechanisms.[20] 

The antigen-specific mechanism suggests that antigen presentation by Langerhans cells or basal keratinocytes leads to the activation of CD4+ helper T cells, stimulating the release of pro-inflammatory T-helper 1 (Th1) cytokines such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFNγ).[21] This induces a CD8+ T cell-mediated cytotoxic reaction against the epidermal basal cell layer resulting in keratinocyte apoptosis via TNF-α, granzyme, or Fas-Fas ligand-mediated mechanisms. 

The non-specific mechanism suggests that the activation of mast cells releases pro-inflammatory mediators such as proteases and the upregulation of matrix metalloproteinases. This results in T cell infiltration of the superficial lamina propria, disruption of the basement membrane, and eventual keratinocyte apoptosis.[20][21] 

The chronic nature of OLP has been postulated to be due to the activation of nuclear factor kappa B (NF-kB) and the inhibition of the transforming growth factor control pathway (TGF-β/Smad), leading to hyperkeratosis and the appearance of distinct white lesions.[22][23] Genetic polymorphisms of the first intron of the promoter gene of IFNγ have also been postulated to be risk factors for developing OLP.[24][25]

Histopathology

The first diagnostic histopathologic criteria for OLP was proposed by the WHO Collaborating Centre for Oral Precancerous Lesions in 1978. They noted that OLP lesions might display the following microscopic features: orthokeratosis or parakeratosis, saw-tooth rete ridges, Civatte bodies, a narrow band of eosinophilic material in the basement membrane, a band-like zone of predominately lymphocytic infiltrate in the superficial lamina propria and liquefaction degeneration in the basal cell layer.[26] 

It was subsequently highlighted that many of these features are not specific to OLP. As such, a recent position paper by the American Academy of Oral and Maxillofacial Pathology (AAOMP) proposed a new set of diagnostic histopathologic criteria in attempting to exclude several of the lichenoid mimics and to improve the accuracy of diagnosis. The proposed criteria now include the following: a band-like zone of predominately lymphocytic infiltrate in the epithelium-lamina propria interface, liquefactive degeneration in the basal cell layer, lymphocytic exocytosis, and the absence of epithelial dysplasia and verrucous epithelial architectural changes.

When examined under direct immunofluorescence, samples from patients with OLP show fibrinogen deposition in a shaggy pattern along the basement membrane zone, without immunoglobulins and complements.[27][28]

Since histologic findings are not specific to OLP, a detailed history taking with clinical correlation is necessary to arrive at a conclusive diagnosis.

History and Physical

Approximately two-thirds of patients with oral lichen planus are symptomatic, presenting with alternating periods of exacerbation and quiescence.[3][29] The intensity of symptoms varies, but patients typically report sensitivity to spicy or acidic foods, painful oral mucosa, mucosal surface roughness, and tightness of the mucosa.[29][2][15] 

There are six clinical subtypes of OLP: reticular, papular, plaque, atrophic, erosive, and bullous.[30] These may be present either individually or in combination with each other, and the classification is usually based on the predominant subtype manifested.[21] 

The most common presentations are the reticular, erosive, and plaque subtypes. Reticular OLP has the most characteristic manifestation and displays a white lacy network (Wickham striae) with hyperkeratotic plaques.[19] Erosive or atrophic OLP typically presents with erythema and ulcerations, often associated with pain and sensitivity. The periphery of the lesions may also display reticular keratotic striae.[21][29] The papular or plaque subtypes appear as white keratotic papules or plaques that may resemble leukoplakia. Patients with a darker skin tone may also exhibit post-inflammatory pigmentation, with diffuse brown or black pigmentation observed together with the lesions.[31] 

OLP typically has a bilateral distribution and most commonly appears on the buccal mucosa, tongue, and gingiva, followed by the labial mucosa and the lower lip.[21] The Koebner phenomenon, where the lesions develop at sites with mechanical trauma (e.g., friction from rough dental restorations/ teeth or lip/cheek biting), may explain why the lesions appear more commonly on the buccal mucosa and tongue, which are more prone to trauma.[32][33] Approximately 10% of OLP patients present with lesions confined to the gingiva, appearing as desquamative gingivitis.[18]

Evaluation

An accurate diagnosis of OLP must be based on thorough history taking, clinical examination, and histopathologic findings. In patients presenting with the characteristic reticular form of OLP, the clinical presentation alone can be sufficiently diagnostic. However, an oral biopsy is still advisable to confirm the clinical diagnosis and to rule out evidence of dysplasia and malignancy.[29] 

For patients who present with desquamative gingivitis, direct immunofluorescence (DIF) may be necessary to rule out autoimmune vesiculobullous diseases that share similar clinical features.[19]

Treatment / Management

There is no cure for oral lichen planus. The primary aim of treatment is to reduce inflammation and provide symptomatic relief. Topical corticosteroids are the first-line treatment for OLP and can be applied as an adhesive gel or used as a mouth rinse. The use of topical agents is preferred as they are effective and are associated with fewer side effects compared to systemic agents. While triamcinolone acetonide gel is commonly used in treating patients with OLP, higher potency corticosteroids such as clobetasol propionate are more effective in providing symptomatic relief.[33][34] 

Patients applying the topical gel are instructed to dry the oral mucosa before application and avoid eating and drinking for 30 minutes after the application to provide sufficient contact time with the oral mucosa. Using mouth rinses such as dexamethasone is particularly beneficial for patients who demonstrate widespread oral lesions or when the lesions are not readily accessible for topical gel application.[35][36] 

Intralesional corticosteroid injections may also be administered to treat persistent erosive OLP.[37] One of the most common side effects of topical corticosteroids is oropharyngeal candidiasis. Clinicians may consider adjunctive therapy with topical/systemic antimycotics if necessary.[38] 

Systemic corticosteroids are primarily used to treat recalcitrant OLP that is resistant to topical therapies, severe OLP with widespread ulceration and erythema, and lichen planus with extra-oral involvement affecting multiple sites.[33][34] The dosage and frequency of use can be reduced as the lesions heal or symptoms improve. 

Second-line therapies can be considered to manage recalcitrant OLP that does not respond to topical corticosteroids. These include calcineurin inhibitors (e.g., cyclosporine, tacrolimus), retinoids, steroid-sparing agents (e.g., azathioprine, hydroxychloroquine), or mycophenolate mofetil. The most common reported side effect from the use of retinoids and cyclosporine is a transient burning sensation, which may limit its use in patients with erosive OLP.[21][39]

Newer calcineurin inhibitors such as tacrolimus should be used with caution, given the Food and Drug Administration (FDA) black box warning regarding the reported increased risk of squamous cell carcinoma and lymphoma.[33] The use of retinoids is also cautioned in pregnant women as it is potentially teratogenic.[40] Steroid-sparing agents such as azathioprine or hydroxychloroquine should also be prescribed carefully due to the risk of bone marrow aplasia and retinal damage, respectively.

Differential Diagnosis

Several conditions resemble oral lichen planus both clinically and histologically. These include oral lichenoid drug reactions, oral lichenoid contact hypersensitivity reactions, mucous membrane pemphigoid, chronic graft-versus-host disease, lupus erythematosus, lichen planus pemphigoides, chronic ulcerative stomatitis, proliferative verrucous leukoplakia, and oral epithelial dysplasia.[41]

The most common medications implicated in oral lichenoid drug reactions include nonsteroidal anti-inflammatory drugs (NSAIDs), antihypertensives, anticonvulsants, antimalarials, and antiretrovirals.[42][43][36] Others include oral hypoglycemics, dapsone, gold salts, penicillamine, phenothiazines.[33][29] 

Lichenoid drug reactions may not necessarily occur immediately, with some lesions developing even years after introducing the medication.[44] Diagnosing a lichenoid drug reaction is difficult, and a thorough clinical history taking may aid in identifying the offending drug. While usually not warranted, discussion with the medication prescriber can be considered to check the feasibility of substituting the medication and monitoring for resolution of the lesions, which may take months.[19][41] 

Oral lichenoid contact hypersensitivity reactions are typically seen on mucosal surfaces in direct contact with the offending agent. These agents may include dental restorative materials (e.g., metals, composites, and glass ionomer cement) or flavoring agents (e.g., cinnamon, menthol, eugenol).[45][42] Amalgam restorations are most commonly implicated in these reactions.[46][47][48] The lesions usually resolve within several months following replacement of the dental restoration or discontinuation of the flavoring agent.[49]

Prognosis

Lifestyle modifications and medication can provide symptomatic relief and improve patients' quality of life. Long-term clinical surveillance will aid in the early detection of malignancy to ensure a favorable long-term prognosis.

Complications

The malignant potential of oral lichen planus remains a highly debated topic in the literature. The reported rate of malignant transformation to squamous cell carcinoma ranges from 0 to 12.5%.[50][51][52][53][54] This wide disparity is due to the marked variations in the inclusion and exclusion criteria of the studies included. The majority of malignancies were detected in patients with atrophic or erosive OLP. 

A recent meta-analysis examining a total of 12,838 OLP patients found that after applying strict inclusion and exclusion criteria, the risk of malignant transformation was found to be 0.44%, significantly lower than most reported studies. Patients who smoke, consume alcohol, are seropositive for Hepatitis C or have a red OLP subtype have a higher risk of malignancy.[55] 

While the reported malignant transformation rates may vary in the literature, all studies unanimously concur that routine long-term follow-up is necessary for managing a patient’s symptoms and ruling out evidence of malignancy.

Deterrence and Patient Education

Patients diagnosed with OLP should always be informed that the treatment is not curative but aimed at providing symptomatic relief. Lifestyle modification to avoid triggers such as acidic or spicy food helps alleviate symptoms.[56][19] The removal of potential exacerbating factors such as smoothening sharp teeth/dental restorations and patient education to maintain optimal oral hygiene and manage stress levels.[3][28][57] 

Highlighting the possibility of malignant transformation is necessary to emphasize the importance of long-term clinical follow-up. Regular patient self-monitoring may also be beneficial to observe for any suspicious changes such as persistent oral ulcerations or growths.

Enhancing Healthcare Team Outcomes

Oral lichen planus can pose a diagnostic dilemma as patients may exhibit non-specific clinical and histologic features that may overlap with several other conditions. A thorough history taking and clinical and histopathological examination are necessary to arrive at an accurate diagnosis. A dentist or oral surgeon is usually involved in caring for patients with OLP. For patients who present with extra-oral involvement, an inter-professional team including dermatologists, gynecologists, gastroenterologists, otorhinolaryngologists, or ophthalmologists may be involved, depending on the sites affected.[6] Pharmacists can also help with drug recommendations, check for drug-drug interactions, verify dosing, and provide patients with medication counseling.

The use of pharmacotherapy, patient education, and lifestyle modification form the cornerstone in managing OLP and ensuring favorable patient outcomes.[33] Future studies may provide more clarity on the pathogenesis and clinical progression of this condition. (Level I)