Lichen Planus

Importance of this disease is related

• Frequency of occurrence
• Occasional similarity to other mucosal disease
• Occasionally painful and persistent nature
• Possible relationship to squamous cell carcinoma

Demographic data

• Age predilection : middle aged, rare for children
• Gender predilection : women
• Distribution : buccal mucosa, particularly posteriorly. The next most common sites are tongue (edges / lateral margins) followed by lips and gingivae. Floor of mouth and palate usually escape

Etiology : unknown

• Generally considered to be an immunologically-mediated process that microscopically resembles a hypersensitivity reaction
• Severity of disease often parallels the patient’s level of stress although no evidence suggests that stress alone is a cause

Pathogenesis

• Initiating factor / event
• Focal release of regulatory cytokines
• Upregulation of vascular adhesion molecules (ELAM-1, ICAM-1, VCAM-1, LFA-1, VLA-4)
• Recruitment and retention of T cells
• Cytotoxicity of basal keratinocytes mediated by T cells

Clinical features of skin lesions

• Types of skin lesions : purple, pruritic, polygonal, papules
• Typically form purplish papules, 2-3mm across with a glistening surface marked by minute fine striae and usually itchy
• Other clinical varities include hypertrophic, atrophic, bullous, follicular and linear forms
• Tend to wax and wane and exhibit a relatively short natural history (1 to 2 years)
• Careful examination of papules reveals a fine, lacelike network of white lines (Wickham’s striae)
• Usually affect the flexor surfaces of extremities, especially the wrists
• Other sites of extraoral involvement : glans penis, vulvar mucosa, nails

Clinical features of oral lesions

Reticular lichen planus	Erosive lichen planus
More common than erosive form	Usually symptomatic
Usually no symptoms	Clinically, atrophic erythematous areas with central ulceration of varying degrees
Involves posterior buccal mucosa bilaterally	Periphery bordered by fine, white radiating striae
Characteristic pattern of interlacing white lines / Wickham’s striae	Desquamative gingivitis when  atrophy and ulceration are confined to the gingival mucosa. Biopsy for light microscopic and immunofluorescent studies of perilesional tissue to differentiate from mucous membrane pemphigoid and pemphigus vulgaris
May appear as papules in some instances	Bullous lichen planus when erosive component is severe and epithelial separation from underlying connective tissue may occur
Wax and wane over weeks or months
Appear more as keratotic plaques with atrophy of papillae on dorsal tongue
Superficial mucoceles may develop within or adjacent

Plaque form	Erythematous/atrophic form	Bullous variant
Resemble leukoplakia clinically but multifocal distribution	Patient may complain of burning, sensitivity, and generalized discomfort	Bullae range from a few mm to cm
Such plaques generally range from slightly elevated to smooth and flat	Red patches with very fine white striae	Such bullae are generally short lived and rupturing leave a painful ulcer
Primary sites are the dorsal tongue and buccal mucosa	Attached gingiva commonly involved	Usually seen on buccal mucosa, especially posterior and inferior regions adjacent to 2nd and 3rd molars
	Patchy distribution often in 4 quadrants	Reticular or striated keratotic areas should be seen with this variant

Typical features of oral lichen planus

• Females account for at least 65% of patients
• Patients usually over 40 years
• Untreated disease can persist for 10 or more years
• Lesions in combination or isolation : striae, atrophic, erosion, plaques
• Common sites are buccal mucosa, dorsum of tongue, gingiva
• Lesions usually bilateral and symmetrical
• Cutaneous lesions only occasionally associated
• Usually good response to corticosteroids

Gingival lichen planus

• Occasionally gingivae are the only site
• Usually atrophic that the gingivae appear shiny, inflamed, and smooth (desquamative gingivitis)
• Striae are uncommon but sometimes present in other parts of mouth
• Only limited segments may be affected
• Plaque accumulation and associated inflammatory changes appear to aggravate lichen planus. Contribution of local irritation to lichen planus is suggested by disappearance of lesions when the teeth are extracted

Features suggesting a lichenoid reaction

• Onset associated with starting a drug
• Unilateral lesions or unusual distributions
• Unusual severity
• Widespread skin lesions
• Localized lesion in contact with restoration. The more sharply defined a lesion is, the more atrophic or ulcerated and the more closely related to a restoration, the more likely it is that removal of the restoration will be effective.

While biopsy is of value to exclude other conditions, it cannot usually distinguish lichen planus from lichenoid reaction

Histopathologic features

• Lichenoid drug reaction, lichenoid amalgam reaction, oral graft-versus-host disease, lupus erythematosus, chronic ulcerative stomatitis, oral mucosal cinnamon reaction may show a similar histopathologic pattern
• Varying degrees of orthokeratosis and parakeratosis
• Varying thickness of spinous layer
• Pointed / “saw-toothed” shape rete ridges
• Hydropic degeneration of basal cell layer
• Intense, bandlike infiltration of predominantly T lymphocytes immediately subjacent to epithelium
• Degenerating keratinocytes (colloid, cytoid, hyaline, Civatte bodies) in area of epithelium and connective tissue interface
• No significant epithelial atypia

Immunopathological features

• Immunopathologic features area nonspecific, deposition of a shaggy band of fibrinogen at the basement membrane
• Direct immunofluorescence demonstrates the presence of fibrinogen in basement membrane in 90% to 100% of cases
• Immunoglobulins and complement factors may be found as well, they are far less common than fibrinogen deposits

Typical histological features of white striae

• Hyperkeratosis or parakeratosis
• Saw tooth profile of rete ridges sometimes
• Liquefaction degeneration of basal cell layer
• Compact, band-like lymphoplasmacytic (predominantly T-cell) infiltrate cells hugging the epithelia-mesenchymal junction
• CD8 lymphocytes predominate in relation to the epithelium

Typical histological features of atrophic lesions

• Severe thinning and flattening of epithelium
• Destruction of basal cells
• Compact band-like, subepithelial inflammatory infiltrate hugging the epithelia-mesenchymal junction

Diagnosis

Reticular lichen planus	Erosive lichen planus
Often based on clinical findings alone	If typical radiating white striae and erythematous atrophic mucosa at periphery of well-dermacated ulcerations on posterior buccal mucosa bilaterally, diagnosis can sometimes be rendered without the support of histopathologic findings
Interlacing white striae bilaterally on posterior buccal mucosa	Biopsy is often necessary to rule out other ulcerative or erosive diseases such as lupus erythematosus or chronic ulcerative stomatitis

Clinical criteria	Histopathologic criteria
Presence of bilateral, more or less symmetrical lesions	Presence of a well-defined bandlike zone of cellular infiltration that is confined to the superficial part of connective tissue, consisting mainly of lymphocytes.
Presence of a lacelike network of slightly raised gray-white lines (reticular pattern)	Signs of liquefaction in the basal cell layer
Erosive, atrophic, bullous and plaque type lesions are accepted only as a subtype in the presence of reticular lesions elsewhere in the oral mucosa	Absence of epithelial dysplasia
In all other lesions that resemble OLP but do not complete the aforementioned criteria, the term “clinically compatible with” should be used	When the histopathologic features are less obvious, the term “histopathologically compatible with” should be used

OLP	OLL
Fullfillment of both clinical and histopathologic criteria	Clinically typical of OLP but histopathologically only compatible with OLP
–	Histopathologically typically of OLP but clinically only compatible with OLP
	Clinically compatible with OLP and histopathologically compatible with OLP

Biopsy should be taken particularly when striae are ill-defined, plaques are present or the lesions are in any other ways unusual.

Differential diagnosis

• Other diseases with a multifocal bilateral presentation : Lichenoid drug reaction, lupus erythematosus, white sponge nevus, hairy leukoplakia, cheek chewing, graft-versus-host disease, candidiasis
• When lesions are plaque-like : idiopathic leukoplakia, squamous cell carcinoma
• Attached gingiva affected : cicatricial pemphigoid, pemphigus vulgaris, chronic LE, contact hypersensitivity, chronic candidiasis

Management

• Check for drugs which might cause lichenoid reaction
• Consider the possibility of superinfection with candida when inflammation worsens or symptoms become more severe
• Biopsy lesions which appear unusual, form homogenous plaques or are in unusual sites
• Check for skin lesions which may aid diagnosis
• Reassurance patient that the condition is not usually of great consequence despite the fact that it can cause constant irritating soreness. Tell patients that the severity waxes and wanes unpredictably and the condition may persist for many years
• Be aware that squamous cell carcinoma may develop in lesions although very rarely
• Follow up lesions associated with reddening, and any unusual in site, appearance or severity

Reticular lichen planus	Erosive lichen planus
Typically produces no symptoms	Corticosteroids are recommended
No treatment required	Fluocinonide / bethamethasone / clotebasol gel applied several times per day to the most symptomatic areas is usually sufficient to induce healing within 1 or 2 weeks
Antifungal therapy if have superimposed candidiasis	Monitor iatrogenic candidiasis associated with corticosteroid use
Annual reevaluation	Evaluate every 3 to 6 months

Use of corticosteroids

• Potent corticosteroids used topically may occasionally promote thrush as a side effect
• Rationale for their use is their ability to modulate inflammation and the immune response
• The addition of antifungal therapy typically enhances clinical results due to elimination of secondary Candida albicans growth in lichen planus- involved tissue
• Triamcinolone dental paste applied to the lesion is an alternative but less effective form of treatment
• Gingival lichen planus is the most difficult to treat. The first essential is to maintain rigorous oral hygiene. Triamcinolone dental paste may be useful as it can readily be applied to affected gingivae
• In unresponsive cases, tacrolimus mouth-rinses may be effective
• In exceptionally severe cases, if topical treatment fails, treatment with systemic corticosteroids is effective
• Lichenoid reactions are treated in exactly the same way as lichen planus with withdrawal of drugs if possible. Thus, the absolute distinction between lichen planus and lichenoid reaction is not always necessary for treatment.

Other medications used

• Systemic and topical Vitamin A analogs (retinoids) : due to their anti-keratinizing and immunomodulating effects. Effects of topical retinoids may be only temporary. Benefits of systemic therapy must be weighed against significant side effects (cheilitis, elevation of serum liver enzyme and triglyceride levels)
• Combinations of systemic steroids, topical steroids, calcineurin inhibitors and retinoids may be used with some success
• Some cases may respond to systemic hydroxychloroquine

Malignant change in lichen planus

• Risk and possible frequency of malignant change has been controversial due to clinical overdiagnosis of lichen planus, coincidental occurrence of lichen planus and oral cancer, microscopic confusion with dysplasia over malignant potential of this disease
• Risk is very low (approximately 1% at 5 years) and more likely associated with erosive and atrophic forms of the disease

References

1. Farah, C., Balasubramaniam, R., & McCullough, M. (2020). Contemporary Oral Medicine. Springer International Publishing.
2. Burket, Greenberg, M., & Glick, M. (2003). Burket’s oral medicine. BC Decker Inc.
3. Regezi, J., Jordan, R., & Sciubba, J. (2017). Oral pathology. Elsevier.
4. Odell, E. Cawson’s essentials of oral pathology and oral medicine.
5. Shafer, W., Hine, M., Levy, B., Rajendran, R., & Sivapathasundharam, B. (2006). A textbook of oral pathology. Elsevier.