Oral Lichen Planus

OLP has been defined as “a chronic inflammatory disorder of unknown etiology with characteristic relapses and remissions, displaying white reticular lesions, accompanied or not by atrophic, erosive and ulcerative and / or plaque-type areas.” Lesions are frequently bilaterally symmetrical. Desquamative gingivitis may be a feature.

Prevalence:

• Estimated prevalence of 1–3% of the population. OLP is the most common mucocutaneous disease of the oral cavity.
• Preference for the female sex
• Increased risk of development after 40 years of age, with a mean age of presentation of 50–55 years .

Malignant Transformation:

In an analysis that exclusively included those publications that met strict quality criteria, the authors observed a malignant transformation rate of 2.28% for OLP.

Risk Factors:

• lingual location
• the presence of atrophic/erosive lesions
• tobacco and alcohol consumption
• human papillomavirus
• hepatitis C virus (HCV)
• presence of aneuploidy

The maximum risk of developing oral cancer is between 3 and 6 years after first diagnosis of OLP.

Patients with OLP and OLLs can develop multiple malignant lesions, which do not always develop at the site of pre-existing lesions. The OSCC that develops in patients with OLP and OLLs shows favorable prognostic parameters, especially in terms of mortality rate.

Clinical Presentation:

The distinctive clinical characteristics of OLP are represented by the presence of white papules that enlarge and fuse to form a reticular, annular or plaque-like pattern, so-called Wickham striae.

• 6 clinical subtypes of OLP have classically been described, which can be observed individually or in combination: reticular, plaque-like, atrophic, erosive/ulcerative, papular and bullous. We discuss 2 subtypes (keratotic/white and erythematous/red).
• Usually present with lesions of more than one subtype simultaneously
• Most commonly affected locations are the buccal mucosa, the lateral and dorsum of tongue and the gingiva
• Almost always a bilateral distribution, which is more or less symmetrical
• Course of OLP is characterized by relapses and remission, with intervals of several weeks or months, both of the clinical signs and symptoms.

Keratotic/White Oral Lichen Planus:

• Most recognized form of OLP, characterized by symmetrical white reticular lesions (Wickham striae) and less frequently as white papules or plaques (Fig. 1).
• The plaque form of OLP appears as a homogeneous, slightly elevated, multifocal white plaque, which typically affects the tongue and buccal mucosa (Fig. 2c).
• Generally asymptomatic – usually an incidental finding during routine examination of the oral cavity by dental practitioners.

Erythematous/Red Oral Lichen Planus: 

• Can present as an area of atrophic mucosa or as red lesions due to hyperemia of the oral mucosa.  
• Areas of erythema can be accompanied by ulceration and are often associated with white keratotic striae (Fig. 4).
• Variety of symptoms, from a mild burning sensation to debilitating pain. Lesions may interfere with speech, chewing and swallowing. 

Desquamative Gingivitis: 

• Erosive lichen planus located on the gums presents as desquamative gingivitis (Fig. 6). 
• OLP is the most common cause of desquamative gingivitis, followed by pemphigoid and pemphigus (23). 
• Buccal gingiva is most commonly affected.

Extra-oral Manifestations:

• 15% of patients with OLP develop cutaneous lichen planus, up to 60% of patients with cutaneous lichen planus have oral manifestations
• Presents as a papulosquamous rash with purplish, flat-topped bumps, of varying size, often described using the “6 Ps” (purple, pruritic, polygonal, planar, papules and plaques), characterized by the classic Wickham striae 
• Typically located on the extremities (Fig. 7) but occasionally presents with generalized involvement and can include the scalp and nails.
• Other anatomical locations that can be affected include the genital mucosa, oesophagus, ocular, urinary, nasal, laryngeal, otic, gastric and anal mucosa. 

Association with Systemic Diseases:

OLP is associated with various systemic diseases, including hepatitis C, hypertension, diabetes and thyroid diseases
Strong evidence that HCV is associated with OLP and is possibly involved in its pathogenesis. It would be prudent to ask patients with OLP about risk factors associated with HCV and to request an HCV antibody determination if concerned.

Differential Diagnoses: 

• Reticular and erythematous lesions: OLLs and discoid lupus erythematosus
• Atrophic and ulcerative forms: pemphigus vulgaris, pemphigoid and liner immunoglobulin (Ig)-A disease (differentiated by reticulation). 
• Plaque form: oral leukoplasia, proliferative verrucous leukoplakia (PVL) 

Regardless of their initial diagnosis, these patients with white multifocal lesions should be carefully monitored for early malignant transformation.

Diagnosis:

• Involves assessing the clinical appearance
• Biopsy and pathology study should be performed to confirm diagnosis due to the need for long-term treatment, and the risk of malignant transformation

Type	Findings
Clinical criteria	Presence of bilateral, more or less symmetrical white lesions affecting the buccal mucosa, tongue, lips, and/or gingiva. Presence of white papular lesions and a lace-like network of slightly raised white lines (reticular, annular, or linear pattern) with or without erosions and ulcerations. Sometimes presents as desquamative gingivitis.
Histopathological criteria	Presence of a well-defined band-like predominantly lymphocytic infiltrate that is confined to the superficial part of the connective tissue. Signs of vacuolar degeneration of the basal and/or suprabasal cell layers with keratinocyte apoptosis. In the atrophic type, there is epithelial thinning and sometimes ulceration caused by failure of epithelial regeneration as a result of basal cell destruction. A mixed inflammatory infiltrate can be found.

Management:

• Main objective of OLP treatment is symptom relief – patients with reticular lesions and other asymptomatic lesions need no treatment 
• First, the triggers and aggravating factors (sharp or broken teeth, poorly fitted prosthesis, etc.) should be identified and excluded.
• Patients should be advised to cease tobacco and alcohol consumption because they can increase the risk of malignant transformation Patients should also be instructed to maintain good oral hygiene, because reducing dental plaque can have a beneficial effect on gingival lesions
• Sodium-lauryl sulphate (SLS) is a foaming agent added to toothpastes that may exacerbate symptoms and SLS-free toothpastes can be used in preference.
• Symptomatic relief can be obtained by using topical anaesthetic agents such as benzydamine hydrochloride 0.15% (as a spray or mouthwash) or lidocaine gel. 
• Topical corticosteroids are the first line agents for treating OLP- A number of preparations are available to be used as mouthwashes: Betamethasone sodium phosphate 500microgram tablets dissolved in 10ml of water up to four times daily, prednisolone 5mg tablets dissolved in 10ml of water or Flixonase 400mcg nasules added to 10ml of water twice daily. Fluticasone propionate spray (50microgram/puff) directed at affected areas 3-4 times daily is useful for isolated lesions. 
• For desquamative gingivitis, preparations with corticosteroids in the form of gel applied in individual custom trays are employed, made in soft clear resin or silicone to increase the contact time

Follow-up

• Due to the risk of malignant transformation, regular follow-up should be conducted to assess for relapse
• The frequency of follow-up visits increases proportionally to the disease activity and symptoms
• At a minimum, the recommendation is an annual follow-up and preferably 2 to 4 annual check-ups based on the signs and symptoms of OLP
• If changes in a lesion are observed during the follow-up visits, a biopsy should be performed and follow-up intervals should be shortened

Lichenoid lesions are red/white intraoral lesions with a reticular striated appearance similar to OLP but are associated with different known stimuli. The lesions can be divided into oral lichenoid contact lesions (OLCLs), drug-induced OLLs and GVHD-induced OLLs.

Oral Lichenoid Contact Lesions:

• OLCL is used to describe oral lesions that resemble lichen planus, both clinically and histopathologically
• Believed to be caused by a localized hypersensitivity reaction (hypersensitivity mediated by delayed immunity) to a dental restorative material (amalgam, gold, nickel, acrylic resin), or other contact agents (e.g., cinnamon)
• Present as white lesions or mixed red/white lesions, occasionally ulcerated. OLCLs are generally less symmetrical and more often unilateral than OLP and can lack the typical reticular appearance of OLP, more typically presenting in the plaque or atrophic form
• Diagnostic characteristic is the topographical location directly related to the suspected causal agent

Drug induced oral lichenoid lesions:

• Caused or associated with exposure to particular drugs and are uncommon, unlike cutaneous OLLs
• There is a long list of systemic drugs associated with the onset of OLLs, which includes non-steroidal anti-inflammatory drugs, anti-hypertensives, oral hypoglycemic agents, antibiotics, antifungals and monoclonal antibodies
• Usually a temporal association between the onset of oral and/or skin lesions and taking certain drugs; however, the drug reaction can occur at any moment, including years after its introduction

Graft-Versus-Host Disease:

• GVHD is a complication that occurs in bone marrow or hematopoietic stem cell transplant recipients
• Systemic condition with a variety of signs and symptoms and affects multiple locations and organs, including the skin, oral cavity, eyes, gastrointestinal tract and liver, as well as other systems such as the lungs, joints and genitourinary tract.
• Oral involvement of GVHD in its acute form is extremely rare; however, the oral cavity is one of the most commonly affected locations in chronic GVHD
• When chronic GVHD affects the oral mucosa, it is clinically characterized by a lichenoid inflammation that frequently involves the tongue and oral mucosa but can affect any location in the oral cavity and can vary from a limited disease with only mild changes to a more extensive and symptomatic disease.
• The clinical changes include papules, white plaques and hyperkeratotic striae that resemble the Wickham striae found in OLP, as well as erythema and pseudomembranous ulcers
• Clinical characteristics by themselves are often sufficient for establishing the diagnosis, provided that they are present in the context of a patient who has undergone allogeneic hematopoietic stem cell transplantation

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