Oral Lichen Planus

A chronic T cell mediated inflammatory disease of the oral mucosa, affecting around 1 to 2 percent of adults, with a female predominance and a peak onset in the fifth and sixth decades.

Pathogenesis

An antigen specific cell mediated immune reaction in which CD8 positive cytotoxic T lymphocytes recognise an antigen associated with basal keratinocytes and induce their apoptosis. This produces the characteristic histological picture of a band like subepithelial lymphocytic infiltrate hugging the basement membrane, basal cell liquefactive degeneration, and apoptotic keratinocytes visible as Civatte bodies. The inciting antigen is unknown in idiopathic disease. Loss of the basal cell layer explains the erosion and the positive direct immunofluorescence pattern of shaggy fibrinogen deposition at the basement membrane zone.

Clinical subtypes

• Reticular: white lacy interlacing striae, that is Wickham striae, typically bilateral on the buccal mucosa. This is the commonest form, is usually asymptomatic, and requires no active treatment.
• Papular: small white papules, often coexisting with reticular disease.
• Plaque like: homogeneous white plaques, particularly on the tongue dorsum, which resemble leukoplakia and require biopsy.
• Atrophic or erythematous: red atrophic areas, frequently affecting the gingivae and producing desquamative gingivitis.
• Erosive or ulcerative: painful erosions and ulcers with peripheral striae, which is the most symptomatic form and which carries the greatest management burden.
• Bullous: rare, with subepithelial blisters that rupture.

Erosive and atrophic forms are the symptomatic ones and are those requiring treatment.

Malignant transformation

This is genuinely contested. Reported transformation rates range from 0.4 to 5 percent, with a pooled estimate around 1 percent. Some of this reflects the inclusion of lesions that were dysplastic from the outset and were misclassified as lichen planus, which is why the term oral lichenoid dysplasia exists and why careful histological review matters. The pragmatic position is that patients with oral lichen planus, particularly erosive and atrophic forms and those on the tongue, require long term surveillance, and that any change in appearance requires biopsy. Do not tell patients the risk is nil, and do not tell them it is high.

Lichenoid reactions, which must be distinguished

• Contact lichenoid reaction: unilateral, in direct contact with an amalgam or other dental restoration, resolving after replacement of the restoration. Patch testing to mercury and other dental materials confirms it.
• Drug induced lichenoid reaction: from angiotensin converting enzyme inhibitors, beta blockers, nonsteroidal anti inflammatory drugs, thiazides, sulfonylureas, antimalarials, gold, penicillamine, allopurinol, and checkpoint inhibitors. It is often unilateral or asymmetrical, may involve unusual sites, and improves after withdrawal, though improvement may take months.
• Graft versus host disease, which produces a clinically identical picture after allogeneic transplantation.
• Lupus erythematosus, with radiating striae and a different immunofluorescence pattern.

Associations

Hepatitis C virus infection has a demonstrated association in some populations, particularly Mediterranean and Japanese, and testing is worthwhile where local prevalence supports it. Associations with diabetes, hypertension and thyroid disease are reported.

• Asymptomatic in reticular disease, discovered at dental examination.
• Burning, soreness and sensitivity to spicy, acidic and hot foods in atrophic and erosive disease.
• Pain on eating, brushing and speaking, which in severe disease produces weight loss and nutritional compromise.
• Desquamative gingivitis with red, sore, peeling gingivae, which patients and clinicians frequently misattribute to poor oral hygiene, leading to more vigorous brushing and worsening of the condition.
• Roughness and altered taste.
• Chronic relapsing and remitting course over years to decades.

Examination

• Wickham striae: fine white lacy or reticular lines, best seen on the buccal mucosa, which are the diagnostic feature and which should be sought at the margin of any erosion.
• Bilateral and roughly symmetrical distribution, which is characteristic. Strictly unilateral disease should raise the possibility of a lichenoid contact reaction or another diagnosis.
• Sites in order of frequency: buccal mucosa, tongue, gingivae, labial mucosa and vermilion. The floor of mouth and palate are uncommonly involved, and lesions there deserve extra scrutiny.
• Erosions with a fibrinous base surrounded by striae.
• Examine the skin for the classical purple polygonal pruritic papules on the flexor wrists and shins, the nails for pterygium and longitudinal ridging, and the scalp for lichen planopilaris with scarring alopecia.
• Examine the genitalia, since vulvovaginal gingival syndrome affects a substantial proportion of women with oral disease and produces scarring, stenosis and considerable distress. It is routinely missed because it is not asked about.
• Ophthalmological and oesophageal involvement occur and produce scarring, so ask about eye irritation and dysphagia.

Red flags requiring biopsy

• Any lesion that changes in appearance, becomes nodular, ulcerated or indurated.
• Unilateral or solitary lesions.
• Lesions on the floor of mouth or the ventrolateral tongue.
• Non healing ulceration despite adequate treatment.
• A plaque like lesion resembling leukoplakia.
• Rapid change.

• Clinical diagnosis is reasonable in classical bilateral reticular disease with typical Wickham striae, but biopsy is required in most other circumstances.
• Incisional biopsy from a representative area including the striae and perilesional mucosa, avoiding the centre of an ulcer where only granulation tissue will be obtained.
• Histology: hyperkeratosis or parakeratosis, a saw tooth rete ridge pattern, basal cell liquefactive degeneration, Civatte bodies, and a dense band like lymphocytic infiltrate confined to the superficial lamina propria. Explicit comment on the presence or absence of epithelial dysplasia must be requested.
• Direct immunofluorescence on fresh or Michel medium transported perilesional tissue, showing shaggy linear fibrinogen deposition along the basement membrane zone, which distinguishes lichen planus from pemphigus vulgaris with intercellular immunoglobulin G, mucous membrane pemphigoid with linear immunoglobulin G and C3 at the basement membrane, and lupus with a granular immunoglobulin band.
• Patch testing to dental materials including mercury, gold, nickel and cobalt where a contact reaction is suspected.
• Medication review with attention to timing of onset relative to drug initiation.
• Hepatitis C serology where local prevalence supports it.
• Full blood count, haematinics, glucose, thyroid function and, where relevant, autoimmune screen.
• Fungal swab, since candidal superinfection is common and worsens symptoms.

There is no cure. Treatment controls symptoms and induces remission of erosions, and asymptomatic reticular disease requires no treatment at all beyond surveillance.

General measures

• Explain the diagnosis clearly: a chronic immune mediated condition, not an infection, not contagious, not caused by poor hygiene, and generally controllable. This addresses the anxiety that drives many consultations.
• Meticulous but gentle oral hygiene with a soft brush, since plaque worsens gingival disease while over vigorous brushing traumatises atrophic mucosa. Regular professional cleaning improves desquamative gingivitis substantially, and this is frequently the most effective single measure for gingival disease.
• Avoid sodium lauryl sulphate containing toothpastes, spicy and acidic foods, alcohol containing mouthwashes, and mechanical trauma from sharp teeth or dentures.
• Smoking and alcohol cessation, both for symptoms and for malignancy risk.
• Replace amalgam restorations in direct contact with a lichenoid lesion where patch testing is positive or where the relationship is clearly topographical, which resolves the lesion in the majority of true contact reactions.
• Substitute a suspected causative drug in discussion with the prescriber, recognising that resolution may take several months.
• Stress management, since exacerbations frequently follow periods of stress.

Topical corticosteroids, first line for symptomatic disease

• Betamethasone sodium phosphate 500 microgram tablets dissolved in 10 mL water, used as a mouthwash for 2 to 3 minutes and spat out, two to four times daily, which is practical for widespread disease.
• Clobetasol propionate 0.05 percent ointment in an adhesive base, applied two to three times daily for localised erosions, which is the most potent option and is highly effective.
• Fluocinonide 0.05 percent or triamcinolone acetonide 0.1 percent in adhesive paste for localised lesions.
• Beclometasone or fluticasone metered dose inhaler sprayed directly onto lesions.
• For desquamative gingivitis, custom made vacuum formed trays holding the corticosteroid gel against the gingivae for 15 to 20 minutes overnight markedly improve delivery and are worth arranging with dental colleagues.
• Prescribe an antifungal alongside prolonged topical steroid, since candidal superinfection is common and undermines treatment. Use nystatin or, with attention to interactions, miconazole.
• Adverse effects of prolonged topical steroid: candidiasis, mucosal atrophy, and with very potent preparations used extensively over long periods, adrenal suppression, which should be considered in patients using large quantities.

Second line topical therapy

• Tacrolimus 0.1 percent ointment applied twice daily, which is effective in steroid refractory erosive disease. Warn about a burning sensation on application in the first days. There is a theoretical concern about malignancy with prolonged calcineurin inhibitor use on mucosa, which is unresolved, and it should be used for defined periods with review.
• Pimecrolimus 1 percent cream as an alternative.
• Ciclosporin mouthwash, which is effective but expensive.
• Intralesional triamcinolone acetonide 10 mg/mL injected into persistent localised erosions, repeated at 2 to 4 week intervals.

Systemic therapy

Reserved for severe, extensive, refractory or multisite disease, and initiated with dermatology or oral medicine involvement.

• Prednisolone 0.5 to 1 mg/kg daily for 4 to 6 weeks then tapered, which reliably controls severe flares but which is unsuitable for long term use.
• Azathioprine 1 to 2.5 mg/kg daily, with thiopurine methyltransferase activity measured before starting, and full blood count and liver function monitoring.
• Mycophenolate mofetil 1 to 2 g daily.
• Methotrexate 7.5 to 20 mg weekly with folic acid supplementation and monitoring of full blood count, liver and renal function.
• Hydroxychloroquine 200 to 400 mg daily, with baseline and annual ophthalmological screening.
• Systemic retinoids such as acitretin, with attention to teratogenicity, hyperlipidaemia and mucocutaneous effects.
• Apremilast and biologic agents in refractory disease under specialist care.

Analgesia and supportive care

• Benzydamine hydrochloride 0.15 percent mouthwash or spray.
• Lidocaine 2 percent gel before meals.
• Chlorhexidine 0.2 percent mouthwash for plaque control, used away from any nystatin dosing.
• Dietary advice and, where weight loss occurs, dietitian referral. Nutritional compromise from painful eating is real and is underestimated.
• Address the psychological impact, which is substantial in chronic painful disease, and screen for anxiety and depression.

Multisite disease

Refer women with oral lichen planus for gynaecological assessment, since vulvovaginal involvement is common, is frequently not volunteered, and causes irreversible scarring and stenosis if untreated. Similarly assess for ocular, oesophageal, cutaneous, nail and scalp involvement, each of which needs its own specialist input.

Surveillance

• Lifelong follow up, with the interval determined by subtype and symptoms: 6 to 12 monthly for stable reticular disease, 3 to 6 monthly for erosive, atrophic and plaque forms, and for tongue and floor of mouth involvement.
• At each visit examine the whole oral cavity, palpate all lesions, photograph and measure.
• Biopsy any change in appearance, any new nodularity or induration, any non healing ulcer, and any lesion behaving differently from the rest.
• Reinforce tobacco and alcohol cessation.
• Instruct the patient to present between appointments with any new ulcer lasting more than 3 weeks, any lump or any change.