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Epithelial nuclei stain positively immunocytochemically and in situ

hybridization for EBV capsid antigen.

Management
Anti-retroviral (ART) and anti-herpes agents (mainly valaciclovir and
famciclovir) may clear the lesion. Topical therapy with podophyllin 25%
and retinoids may also help. Cryotherapy has been reported as successful.

Prognosis
Appears to be benign, and self-limiting, but recurrences are common.

Lichen planus (LP) and lichenoid

reactions
Definition: A mucocutaneous disorder characterized variably by oral,
genital and/or skin lesions.
Prevalence (approximate): Possibly 1% of the population.
Age mainly affected: Middle-age and older.
Gender mainly affected: F > M.
Etiopathogenesis: A minority of cases have an identifiable offending
agent such as drugs (e.g. antihypertensives, antidiabetics, gold salts,
non-steroidal anti-inflammatory agents, antimalarials) or dental materials (amalgam, gold or others), or may arise in graft-versus-host disease
(GVHD), HIV infection or hepatitis C (Figure 39.2). These are often
termed lichenoid lesions. The etiology in most patients, however, is
unclear (idiopathic LP).
Upregulation of epithelial basement membrane extracellular matrix
proteins and the secretion of cytokines and intercellular adhesion
molecules by keratinocytes facilitates ingress of T-lymphocytes which
attack stratified squamous epithelia (Figure 39.3). Auto-cytotoxic CD8+
T-cells bind to keratinocytes and trigger the programmed cell death
(apoptosis) of basal cells via tumor-necrosis factor alpha (TNF-alpha)
and interferon gamma (IFN-gamma). TNF-alpha stimulates activation of
nuclear factor kappa B (NF-kB) and production of inflammatory cytokines.
Inhibition of transforming growth factor beta which normally causes
keratinocyte proliferation can lead to atrophic forms of LP. Genetic
polymorphism of IFN-gamma is a risk factor for development of oral
lesions, whereas TNF-alpha allele may be a risk factor for LP affecting
mouth and skin.

Diagnostic features
History
Oral: Lesions may be asymptomatic or may cause soreness, especially
if atrophic or erosive.
Extraoral: Typically an itchy rash, or genital soreness (Figure 39.4).
Clinical features
Oral: Typically, lesions are:
bilateral
posterior in the buccal (cheek) mucosa
sometimes on the tongue, floor of mouth or gingivae
rare on the palate
Presentations typically include white:
network of raised white lines or striae (reticular pattern)
(Figures 39.5ab and Figure 39.6)
papules
plaques, simulating leukoplakia
Erosions are less common, persistent, irregular, and painful, with
a yellowish slough (plus white lesions). Red atrophic areas and/or
desquamative gingivitis may be seen.

Some lesions may be associated with hyperpigmentation.

Lichenoid oral lesions clinically and histologically resemble LP but
may:
be unilateral
be associated with erosions
affect particularly the palate and tongue.
Extraoral: LP may also affect:
Skin; itchy (pruritic), purple, polygonal, papules especially on the
flexor surface of the wrists (Figure 39.7). These may have white
Wickham striae. Trauma may induce lesions (Koebner phenomenon).
Genitals; white or erosive lesions (if there is also oral involvement,
these are termed vulvovaginal-gingival or penile-gingival syndromes).
Esophagus; white or erosive lesions.
Nails; ridging.
Hair; loss.
Differential diagnosis: Lupus erythematosus, leukoplakia, keratosis,
malignancy, chronic ulcerative stomatitis, pemphigus, pemphigoid.
Investigations
Optional Blood tests may help exclude liver disease (hepatitis C) and
diabetes.
Biopsy/histopathology; history and clinical appearance are usually
highly indicative of the diagnosis but lesional biopsy is often indicated,
particularly to differentiate from other conditions and exclude malignancy. Histological features of LP may include (Figure 39.8):
a dense subepithelial cellular infiltrate including mostly T-lymphocytes
hyperkeratosis and thickening of the granular cell layer
basal cell liquefaction degeneration and colloid bodies
saw-tooth appearance of rete pegs
immunostaining for fibrin at the epithelial basement membrane
zone.
It can be a problem in histopathology to characterize lichen,
lichenoid and microscopically similar lesions, including sometimes
leukoplakia.

Management
Predisposing factors should be excluded. If amalgams might be
implicated, it may be worthwhile considering removing them. If
drugs are implicated, the physician should be consulted as to possible
alternatives.
Oral lesions may respond to the more potent topical corticosteroids
(e.g. clobetasol, beclomethasone, or budesonide). Antifungals may be
helpful.
Widespread, or severe, or recalcitrant lesions can be managed with
intralesional or stronger topical corticosteroids.
Specialist referral may be indicated if there is concern about
malignancy, extraoral lesions, diagnosis, or recalcitrant oral lesions
(Figure 39.9). Topical tacrolimus or ciclosporin, or systemic immunosuppressive agents (e.g. corticosteroids, azathioprine, ciclosporin or
dapsone) or vitamin A derivatives (e.g. isotretinoin) may be required.
Persons with lichen planus should be advised to stop any tobacco/
alcohol/betel habits, and should be encouraged to have a diet rich in
fruit and vegetables.

Prognosis
Oral LP is often persistent but benign. Although controversial it is
generally accepted that there is about a < 3% chance of malignant
transformation over five years, predominantly in those with longstanding LP.
Hairy leukoplakia, lichen planus

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