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can occasionally mimic oral precancerous
lesions or other significant conditions
makes it important for all dentists to be
aware of its clinical features. Practitioners
should also know the additional steps that
can be taken to confirm a clinical diagno-
sis of oral lichen planus, including inci-
sional biopsy for routine histopathologic
evaluation and direct immunofluorescent
examination. Finally, as some patients
with oral lichen planus are symptomatic
and desire treatment, clinicians should be
aware of current management strategies.
Since a significant percentage of oral
lichen planus patients will also have
cutaneous involvement, skin lesions can
be used to help support the clinical or
working diagnosis. e classic skin lesions
of lichen planus have been described as
purple, polygonal, pruritic papules that
are usually found in small clusters on the
flexor aspects of the extremities ().
ichen planus is a chronic,
immunologically mediated
condition first described as a
disease of the skin that can
also affect mucosal surfaces,
including those that line the oral cavity.
Oral lichen planus has been estimated
to affect from 0. percent to 4 percent
of the population. Interestingly, while
more than one-third of patients with
cutaneous lichen planus will report-
edly have oral involvement, only about
5 percent of patients with oral lichen
planus ever develop skin lesions.2,3
Although the etiology is unknown,
most authorities agree it represents a
form of autoimmune disease in which
dysregulation of T lymphocyte function
results in damage to, or destruction of,
basal cells of the surface epithelium.4,5
e relatively high prevalence of oral
lichen planus makes it likely that virtually
every dentist who treats adult patients
will encounter this condition. e fact that
the mucosal changes in oral lichen planus
(Courtesy of
Doug D. Damm, DDS, Lexington, Ky.)
(Wickham’s striae)
Fine, interlacing whitish lines known
as Wickham’s striae can occasionally be
observed on the surface or periphery of
the flat-topped papules and plaques. Dys-
trophic nail changes develop in some pa-
tients and females can have vulvo-vaginal
involvement that may be symptomatic.3,6
Oral lichen planus usually devel-
ops in middle-aged adults, and women
are affected more often then men. It
is quite uncommon in childhood, al-
though affected patients often have
associated cutaneous disease and a
predisposition among children of Asian
descent has been reported.7-9 Several
variants of oral lichen planus have been
described, however, two major forms
are recognized: reticular and erosive.
Reticular oral lichen planus represents
the most common clinical pattern of
this disease. e word reticular refers to
the net-like or lacy pattern of interlacing
keratotic lines (also denoted as Wickham’s
striae) that is characteristic of oral lichen
planus. Reticular oral lichen planus is usu-
ally asymptomatic and bilateral involve-
ment of the posterior aspects of the buccal
mucosa that may extend into the vesti-
bules is virtually pathognomonic for this
condition (). Some
cases are predominated by small keratotic
papules that may be interconnected by
thin keratotic striae. With involvement of
the dorsal aspect of the tongue, a lace-like
quality may not be present and lesional
tissue will often appear as single or multiple
keratotic plaques with loss or coales-
cence of the filiform papillae ().
e lesions of oral lichen planus
tend to wax and wane in their clinical
severity without any treatment. Many
patients report nothing more than a
vague awareness of tissue “roughness.”
Concomitant involvement of other mu-
cosal sites, most often the gingivae, the
dorsal and lateral aspects of the tongue
and vermilion border, may be noted.
e erosive form of oral lichen planus is
much less common than the reticular form
and differs in that most patients report
symptoms with their oral lesions. Affected
mucosa usually presents as an area of atro-
phy and erythema with variable zones of
central erosion or ulceration and a periph-
eral border of fine, radiating keratotic striae.
Affected sites are similar to those seen with
reticular oral lichen planus and it is not
uncommon to see both forms of the disease
manifest in the same patient ().
Occasionally, lesional changes are relatively
confined to the attached gingival or alveolar
mucosa, producing a clinical pattern that
has been termed “desquamative gingivi-
tis” (). Rarely, the erosive aspect
of the disease is so severe that epithelial
separation may occur and vesicle or bulla
formation may be observed clinically.
As with the reticular form, erosive oral
lichen planus tends to have a bilateral or
multifocal mucosal presentation with pe-
riods of remission and exacerbation rather
than steadily progressing course (
). Symptoms can vary from mild
discomfort to severe pain that interferes
with normal mastication or speaking.
Even without a history or evidence
of cutaneous lichen planus, reticular oral
lichen planus with bilateral involvement
of the buccal mucosa has such a character-
istic pattern that clinical diagnosis alone
is usually sufficient. It should be empha-
sized that even in “classic” cases, periodic
patient re-evaluation would be warranted
to detect any progressive tissue changes,
and the patient should be advised to
consider tissue biopsy in order to provide
a firm, baseline histopathologic diagnosis.
e finding of a single area or an
isolated mucosal lesion with a reticular
or lichenoid appearance is not char-
acteristic of oral lichen planus and is
(Courtesy of Carl M, Allen, DDS, MS, Columbus, Ohio.)
more suggestive of conditions such as a
lichenoid drug or contact hypersensitiv-
ity reactions (see related manuscript in
this issue). To complicate matters, some
oral lichen planus patients with gener-
alized mucosal involvement may also
have similar lesions localized to areas in
direct contact with amalgam restorations
(lichenoid amalgam reaction).0 Careful
history taking and clinical correlation may
be helpful in assigning a working diag-
nosis and a biopsy is usually warranted.
In presentations limited to keratotic
plaque(s) of the dorsal, and especially
dorsolateral, tongue, a biopsy would
be mandatory to exclude the possibil-
ity of dysplasia (precancerous epithelial
change) or squamous cell carcinoma.
For patients with suspected erosive
oral lichen planus, the differential diag-
nosis can be quite broad. A biopsy should
be recommended to support or confirm
the clinician’s working diagnosis and ex-
clude other and potentially more serious
conditions. Depending upon the precise
clinical setting, the differential could
include epithelial dysplasia, squamous cell
carcinoma, lichenoid reactions to drug,
foreign body, amalgam, or other contact
agents (such as artificial cinnamon flavor-
ing), lupus erythematosus and chronic
ulcerative stomatitis.,2 In patients with
a history of bone marrow transplanta-
tion, the complication known as graft
versus host disease can closely mimic the
clinical features of oral lichen planus.2
If a desquamative gingivitis-like pre-
sentation predominates, conditions such
as lichenoid foreign body reaction (pos-
sibly to dental prophylaxis materials), mu-
cous membrane (cicatricial) pemphigoid,
chronic ulcerative stomatitis and pemphi-
gus vulgaris would need to be considered.
erefore, a biopsy should be considered
for any case of persistent desquama-
tive gingivitis that does not respond to
conservative local hygiene measures.
Submission of tissue for both routine and
direct immunofluorescent examination
will permit the exclusion or confirmation
of a specific autoimmune disease, such as
pemphigus vulgaris, as quickly as possible.
It should also be noted that oral
lichen planus, reticular and erosive forms
alike, may become complicated by the
acquisition of superficial fungal micro-
organisms, usually Candida albicans. In
most cases, this probably represents an
opportunistic infection since Candida
consume keratin and this substance is
readily available in the keratotic papules
and striae produced by oral lichen planus.
Superimposed candidiasis may lead
to mild “burning” discomfort of the
affected mucosa, even in reticular oral
lichen planus, and can further compli-
cate the diagnosis by masking the classic
net-like pattern of the keratotic striae.
Cytologic or culture studies can aid in the
management of these cases by providing
positive identification of the microorgan-
isms. Even without diagnostic tests, an
empirical course of appropriate antifungal
therapy (such as clotrimazole troches
or fluconazole tablets) may unmask the
characteristic clinical features of the
underlying oral lichen planus and help
reduce candidiasis-related symptoms.
e final diagnosis of oral lichen
planus, especially in cases of erosive
disease, often rests with a tissue biopsy of
affected mucosa. Following appropriate
local anesthesia, an elliptical wedge should
be obtained that extends from lesional
tissue into adjacent normal mucosa. Use
of cautery methods is not recommended
for this purpose due to artifactual changes
they often induce within the specimen. In
addition, erosive or ulcerated lesions must
be handled gently to minimize the chance
of peeling or splitting the surface epithe-
lium from the underlying connective tissue,
greatly degrading the diagnostic usefulness
oral vesiculo-bullous diseases like mucous
membrane (cicatricial) pemphigoid or
pemphigus vulgaris. In contrast, most
dentists and physicians are unfamiliar
with chronic ulcerative stomatitis, a
specific mucocutaneous autoimmune
disease first described in 990 that can
mimic the clinical features of oral lichen
planus.2-4 Chronic ulcerative stomatitis
is associated with the development of
Direct immunofluorescent testing of
oral lichen planus specimens is similar to
routine histopathologic examination in
that the results can be suggestive of or
consistent with the diagnosis of oral lichen
planus, but they are not specific to oral
lichen planus alone. Most lesions demon-
strate an irregular linear band of fibrinogen
deposition at the basement membrane
zone, a feature shared with other forms
of lichenoid mucositis (see related manu-
script is this issue), graft versus host
disease, lupus erythematosus and chronic
ulcerative stomatitis. e distinguishing
feature for chronic ulcerative stomatitis
patient specimens is the additional find-
ing of punctuate (dot-like), intranuclear
deposits of IgG in the basilar cells of the
surface stratified squamous epithelium.
Patients with chronic ulcerative sto-
matitis have been shown to respond best
to treatment with hydroxychloroquine
(Plaquenil) and are usually resistant to ini-
tial treatment measures recommended for
oral lichen planus patients. is provides
a persuasive rationale for obtaining both
routine and direct immunofluorescent
examination in all cases of erosive oral
lichen planus. Although chronic ulcer-
ative stomatitis has been described as
an uncommon or even rare autoimmune
disease, the number of cases masquerad-
ing as oral lichen planus could be substan-
tial due to similarities in their clinical and
even routine histopathological features.
Patients should be advised that the benefit
of a correct diagnosis (including exclusion
of other forms of autoimmune disease
like pemphigoid or pemphigus) and early
initiation of effective treatment for the pa-
tient more than justifies the added cost of
baseline direct immunofluorescent testing.
Unlike cutaneous lichen planus, which
is usually self-limited and spontane-
ously resolves within one to two years,
circulating autoantibodies to a nuclear
antigen in stratified squamous epithe-
lium known as p63. For this reason,
chronic ulcerative stomatitis has also been
compared to both oral lichen planus and
lupus erythematosus, another autoim-
mune disease that is characterized by the
production of anti-nuclear antibodies.
e majority of chronic ulcerative
stomatitis patients have been older adult
women, and some patients have also
presented with erosive or bullous skin
lesions. Intraorally, the most commonly
affected site is the tongue, followed by the
labial or buccal mucosa and gingiva.4 Sim-
ilar to erosive oral lichen planus, lesions
appear as shallow, irregular ulcerations
but peripheral keratotic striae, if present,
are usually abbreviated or vaguely formed.
Gingival involvement produces a clinical
presentation of desquamative gingivitis.
of the specimen. When it is important to
exclude specific vesiculobullous conditions
such as mucous membrane pemphigoid, a
separate sample must be obtained for direct
immunofluorescent examination because
the routine formalin fixative interferes with
direct immunofluorescent processing.
is can be accomplished with two
separate biopsies, but can also be man-
aged through careful planning and harvest
of a single incisional specimen. Ideally, a
“double-duty” biopsy should extend from
just within the border of lesional tissue to
several millimeters into normal-appear-
ing mucosa. An overall length of 8 mm
to 0 mm ensures adequate sampling for
both studies. Once the tissue is removed,
it can be carried to a table or sterile gauze
and split across the short axis with a
sharp scalpel. e “lesional” half of the
specimen should be placed in formalin
for routine histopathologic examination.
e “normal” half can then be placed in
Michel’s solution, a special liquid medium
designed for direct immunofluorescence.
Oral lichen planus has several charac-
teristic histopathologic features, including
hyperkeratosis, vacuolar degeneration
of the basal cell layer and degenerating
keratinocytes termed colloid or Civatte bod-
ies. Rete ridges may be absent or elongated
with a pointed or “saw-tooth” appearance. A
band-like infiltrate of small lymphocytes is
seen immediately subjacent to the epithe-
lium, occasionally destroying the epithelial-
connective tissue interface. Unfortunately,
these features are not specific to oral lichen
planus and can be seen in several other
conditions, such as lichenoid amalgam
reaction, lichenoid drug reaction, mucosal
cinnamon reaction, lupus erythematosus,
graft versus host disease, and chronic
ulcerative stomatitis. As a result, oral lichen
planus is a diagnosis that demands careful
correlation of the clinical setting with the
results of routine biopsy examination.
Many practitioners are familiar with
oral lichen planus is more commonly
a chronic condition that often persists
for multiple years, if not decades.,7 As
with most forms of autoimmune disease,
there is no cure for oral lichen planus.
e primary goals of treatment are to
reduce the length and severity of disease
during periods of activity and, if possible,
increase the periods of disease quiescence.
As mentioned, patients with asymp-
tomatic reticular oral lichen planus do
not require therapeutic intervention.
Conservative measures to improve oral
hygiene and minimize local tissue irrita-
tion may help reduce periods of notable
tissue “roughness.” ese could include
decreasing the interval between profes-
sional dental prophylaxis (every four
months instead of every six months),
recommending the use of bland tooth-
paste or mouthrinse formulas and
smoothing/repairing sharp or broken
teeth, restorations, or prostheses. In
the case of superimposed candidiasis,
antifungal therapy would be appropri-
ate to relieve associated symptoms.
Treatment of symptomatic erosive oral
lichen planus is largely based on the use of
topical corticosteroids, especially the higher
potency formulations such as fluocinonide
(Lidex) 0.05 percent, augmented beta-
methasone (Diprolene) 0.05 percent and
clobetasol (Temovate) 0.05 percent. Gel
formulations are preferable to creams or
ointments as the latter are more hydropho-
bic and adhere poorly to the normally moist
oral mucosa. Patients should be advised to
apply the corticosteroid gel in a thin film
directly to the lesional tissue four to five
times daily. Emphasis should be placed on
the use of tiny amounts of the gel multiple
times a day rather than large amounts less
often. After symptoms subside, patients
can simply stop applying the gel without
tapering the dosing schedule. Since oral
lichen planus has a natural waxing/wan-
ing course, patients should be instructed
to re-institute their topical therapy at full
strength whenever symptoms return. Den-
tists and hygienists should also encourage
patients to improve or maintain excellent
oral hygiene measures as this step leads to
decreased disease activity, with or with-
out topical corticosteroid treatment.6,8
In addition, it is important to inform
the patient that while this treatment has
not been approved in the United States by
resulting from mild local immunosup-
pression), however, are readily resolved
with concomitant antifungal therapy.
For patients with widespread symp-
tomatic disease or who have limited
manual dexterity, possibly secondary to
underlying conditions such as arthritis,
aqueous corticosteroid solutions may be
an effective alternative to gel formula-
tions. Options include dexamethasone
(Decadron) elixir, 0.5 mg/5 ml and
prednisolone (Prelone) syrup, 5 mg/5
ml. Patients should be instructed to
swish the solution over affected areas for
a minute or so and expectorate without
rinsing after meals and before bedtime.
A variety of other medications have
been used in treating oral lichen planus,
including other topical immunosuppres-
sives (tacrolimus, retinoids, cyclosporine),
systemic agents (corticosteroids, retinoids,
dapsone, azathioprine, griseofulvin,
thalidomide, levamisole), and PUVA (oral
psoralen and low-dose ultraviolet A) or
laser therapy.,6,,2,6 Although encouraging
results have been reported, these agents are
typically more expensive than topical cor-
ticosteroid therapy without clear evidence
of superior efficacy. Currently, their use
should be reserved for erosive oral lichen
planus patients who prove recalcitrant
to topical corticosteroid treatment and
prescribed under the guidance of a dental
(i.e., an oral and maxillofacial pathologist)
or medical specialist, i.e., a dermatologist.
Numerous studies have addressed this
important question; however, a definitive
answer remains elusive.,6,9 Evidence
from some reports indicates that patients
with oral lichen planus, particularly those
with erosive or atrophic forms, have an
increased risk for the development of oral
squamous cell carcinoma. Others have
suggested that case reports or case series
.
the Food and Drug Administration, it is
considered a well-documented “off-label”
use for formulations originally marketed
to treat skin conditions such as cutaneous
lichen planus. More than three decades
of scientific studies have shown these
agents to be safe and efficacious in manag-
ing patients with oral lichen planus, yet
no pharmaceutical company has pursued
the costly process required by the FDA to
receive formal approval for this applica-
tion. It can be pointed out that significant
complications from topical corticosteroid
treatment of oral lichen planus have been
rare, and only in cases where the patient
substantially and improperly overused their
medication. On the other hand, clinicians
should also be aware that oral candidiasis
is not an uncommon minor complica-
tion of topical corticosteroid therapy.
ese opportunistic infections (probably
of oral lichen planus that have undergone
“malignant transformation” probably
represent cases of oral epithelial dysplasia
(precancerous change) that were misdiag-
nosed (clinically, microscopically or both)
as oral lichen planus. In their recent review,
Lodi et al. pointed out that oral lichen
planus could be confused, both clinically
and microscopically, with the condition
known as proliferative verrucous leukopla-
kia.6 Patients with proliferative verrucous
leukoplakia may present with multiple leu-
koplakic areas throughout the oral cavity.
Lesions of proliferative verrucous leukopla-
kia are considered precancerous with a sig-
nificant rate of malignant transformation.
Obviously, the distinction between
oral lichen planus and premalignant
lesions is critical. For this reason, oral bi-
opsy specimens should be interpreted by
oral and maxillofacial pathologists, who
are specifically trained in both the micro-
scopic and clinical diagnosis of mouth
diseases. With their experience in clinico-
pathologic correlation, oral and maxil-
lofacial pathologists are uniquely suited
to provide an accurate diagnosis for these
challenging cases and, if needed, to assist
in patient management or follow-up.
Science has known for years that cancer
is essentially a genetic disease that results
from nonlethal damage to cellular DNA.
Different patterns of damage can be seen
in different forms of cancer and several
chromosomal sites have been recognized as
important to the development of epithelial
dysplasia and oral squamous cell carcinoma.
To date, the only molecular studies to
address the issue of DNA damage in oral li-
chen planus have been presented by Zhang
et al. using comparative genetic analysis of
biopsy material to detect evidence of allelic
loss or loss of heterozygosity at three differ-
ent chromosomal sites related to oral squa-
mous cell carcinoma.20 Analysis of multiple
examples of different oral mucosal lesions,
including cases of oral lichen planus, benign
reactive hyperplasia, various degrees of
dysplasia and oral squamous cell carcinoma
was performed. Among the oral lichen
planus specimens, evidence of loss of het-
erozygosity was lower than that for reactive
hyperplasia (6 percent versus 4 percent)
and was significantly lower in comparison
to mild, moderate, or severe dysplasia/car-
cinoma-in-situ (40 percent, 46 percent,
and 8 percent, respectively) as well as oral
squamous cell carcinoma (9 percent). e
mentioned previously, baseline biopsy
with direct immunofluorescent is recom-
mended in all cases of erosive oral lichen
planus to establish the diagnosis. Subse-
quently, any lesional tissue that appears to
worsen progressively despite appropriate
therapy should be viewed with suspicion
and undergo biopsy (or re-biopsy) as soon
as possible. Oral lichen planus may not
be a premalignant condition, but neither
does it preclude a patient from developing
a second disease, including oral cancer.
In patients with classic reticular oral
lichen planus, the diagnosis can often be
made on the basis of clinical features alone.
Patients should be advised as to the chronic
nature of their disease and its tendency to
exhibit periods of activity that alternate
with times of relative quiescence or remis-
sion. Biopsy confirmation of oral lichen
planus should be considered, especially
with symptomatic erosive disease, and the
use of direct immunofluorescent is strongly
recommended to exclude more spe-
cific forms of autoimmune disease. Most
cases of oral lichen planus can be managed
through the use of topical corticosteroids
and good oral hygiene measures. While the
most current molecular evidence does not
suggest oral lichen planus to be a precan-
cerous condition, clinicians are advised to
closely monitor their oral lichen planus
patients for any intraoral lesion that does
not respond to normal therapeutic mea-
sures. Regardless of a previous diagnosis
of oral lichen planus, tissue biopsy and
histopathologic evaluation should always be
recommended for any persistent or progres-
sive area of mucosal abnormality.
Crit Rev Oral Biol Med
J Am Acad Dermatol
follow-up study examined dysplastic lesions
that mimicked oral lichen planus under the
microscope (so-called lichenoid dysplasia)
and found high levels of loss of heterozy-
gosity in these cases that were essentially
identical to dysplastic lesions lacking a
resemblance to oral lichen planus.2
Confirmation of these results by other
scientists is needed. It is possible that
DNA damage occurs in oral lichen planus,
but not in areas of the chromosomes that
would have been detected by the panel
of probes used by Zhang and co-authors.
Overall, however, their molecular find-
ings would argue that oral lichen planus
is probably not a premalignant condition.
e problem, particularly with erosive oral
lichen planus, is that lesional tissue can oc-
casionally resemble areas of erythroplakia,
a clinical presentation that is suspicious
for precancerous or cancerous change. As
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
Crit Rev Oral Biol Med
Oral Surg Oral Med
Oral Pathol Oral Radiol Endod
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Pediatr Dermatol
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Arch Dermatol
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J Can Dent Assoc
J Am Acad
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Oral Surg Oral Med Oral Pathol Oral Radiol Endod
Oral
Surg Oral Med Oral Pathol Oral Radiol Endod
Oral Surg
Oral Med Oral Pathol Oral Radiol Endod
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J Oral Pathol Med
Oral Surg Oral Med Oral Pathol Oral
Radiol Endod
Am J Pathol
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