Oral Lichen Planus an Update on Pathogenesis and Treatment

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Oral lichen planus An update on pathogenesis and treatment

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J Oral Maxillofac Pathol. 2011 May-Aug; 15(2): 127–132.
doi: 10.4103/0973-029X.84474
PMCID: PMC3329692

Oral lichen planus: An update on
pathogenesis and treatment
N Lavanya, P Jayanthi, Umadevi K Rao, and K Ranganathan
Department of Oral and Maxillofacial Pathology, Ragas Dental College and Hospital, Uthandi,
Chennai, India
Address for correspondence:Dr. N Lavanya, Senior Lecturer, Department of Oral and
Maxillofacial Pathology, Ragas Dental College, 2/102, East Coast Road, Uthandi, Chennai 600 119, India. E-mail: lavanyabds/at/yahoo.com
Copyright : © Journal of Oral and Maxillofacial Pathology
This is an open-access article distributed under the terms of the Creative Commons AttributionNoncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

ABSTRACT
Oral lichen planus (OLP) is a chronic inflammatory disease that affects the mucus membrane of
the oral cavity. It is a T-cell mediated autoimmune disease in which the cytotoxic CD8+ T cells
trigger apoptosis of the basal cells of the oral epithelium. Several antigen-specific and
nonspecific inflammatory mechanisms have been put forward to explain the accumulation and
homing of CD8+ T cells subepithelially and the subsequent keratinocyte apoptosis. A wide
spectrum of treatment modalities is available, from topical corticosteroids to laser ablation of the
lesion. In this review, we discuss the various concepts in the pathogenesis and current treatment
modalities of OLP.
Keywords: Apoptosis, autoimmune, basal keratinocytes, corticosteroids, oral lichen planus

INTRODUCTION
Lichen planus is a chronic inflammatory disease that affects the skin and the mucus membrane.
Oral lichen planus (OLP), the mucosal counterpart of cutaneous lichen planus, presents
frequently in the fourth decade of life and affects women more than men in a ratio of 1.4:1.[1]
The disease affects 1–2% of the population.[2,3] It is seen clinically as reticular, papular, plaquelike, erosive, atrophic or bullous types. Intraorally, the buccal mucosa, tongue and the gingiva are
commonly involved although other sites may be rarely affected.[4] Oral mucosal lesions present
alone or with concomitant skin lesions. The skin lesions present as violaceous flat-topped
papules in ankles, wrist, and genitalia, but characteristically the facial skin is spared.

The etiology and pathogenesis of OLP has been the focus of much research, and several antigenspecific and nonspecific inflammatory mechanisms have been put forward to explain the
pathogenesis. Although mostly palliative, a spectrum of treatment modalities is in practice, from
topical application of steroids to laser therapy. In this review, we discuss the recent concepts in
the pathogenesis and current treatment modalities of OLP.

PATHOGENESIS
OLP is a T-cell mediated autoimmune disease in which the auto-cytotoxic CD8+ T cells trigger
apoptosis of the basal cells of the oral epithelium.[5] An early event in the disease mechanism
involves keratinocyte antigen expression or unmasking of an antigen that may be a self-peptide
or a heat shock protein.[1,6] Following this, T cells (mostly CD8+, and some CD4+ cells)
migrate into the epithelium either due to random encounter of antigen during routine surveillance
or a chemokine-mediated migration toward basal keratinocytes.[1] These migrated CD8+ cells
are activated directly by antigen binding to major histocompatibility complex (MHC)-1 on
keratinocyte or through activated CD4+ lymphocytes. In addition, the number of Langerhan cells
in OLP lesions are increased along with upregulation of MHC-II expression; subsequent antigen
presentation to CD4+ cells and Interleukin (IL)-12 activates CD4 + T helper cells which activate
CD8+ T cells through receptor interaction, interferon γ (INF – γ) and IL-2. The activated CD8+
T cells in turn kill the basal keratinocytes through tumor necrosis factor (TNF)-α, Fas–FasL
mediated or granzyme B activated apoptosis.[1,6]

A CYTOKINE-MEDIATED LYMPHOCYTE HOMING
MECHANISM
Attraction of the lymphocytes to the epithelium–connective tissue interface has also been
proposed to be due to cytokine-mediated upregulation of adhesion molecules on endothelial cells
and concomitant expression of receptor molecules by circulating lymphocytes. In OLP, there is
increased expression of the vascular adhesion molecules (CD62E, CD54, CD106) by the
endothelial cells of the subepithelial vascular plexus.[7] The infiltrating lymphocytes express
reciprocal receptors (CD11a) to these vascular adhesion molecules. This supports the aboveexplained hypothesis that the cytokine-mediated lymphocyte homing mechanism plays an
important role in the pathogenesis of lichen planus. Some of the cytokines that are responsible
for the upregulation of the adhesion molecules are: TNF-α, IFN-γ and IL-1. These are derived
from the resident macrophages, Langerhans cells, lymphocytes and the overlying keratinocytes
themselves, thus setting up a vicious cycle.[7]
The normal integrity of the basement membrane is maintained by a living basal keratinocyte due
to its secretion of collagen 4 and laminin 5 into the epithelial basement membrane zone. In turn,
keratinocytes require a basement membrane derived cell survival signal to prevent the onset of
its apoptosis. Apoptotic keratinocytes are no longer able to perform this function, which results
in disruption of the basement membrane. Again, a non-intact basement membrane cannot send a
cell survival signal. This sets in a vicious cycle which relates to the chronic nature of the disease.
[1,8]

The matrix metalloproteinases (MMP) are principally involved in tissue matrix protein
degradation. MMP- 9, which cleaves collagen 4, along with its activators is upregulated in OLP
lesional T cells, resulting in increased basement membrane disruption.[9]
RANTES (Regulated on Activation, Normal T-cell Expressed and Secreted) is a member of the
CC chemokine family which plays a critical role in the recruitment of lymphocytes and mast
cells in OLP. CCR1, CCR3, CCR4, CCR5, CCR9 and CCR10, which are cell surface receptors
for RANTES, have been identified in lichen planus.[1,10] The recruited mast cell undergoes
degranulation under the influence of RANTES, which releases chymase and TNF-α. These
substances upregulate RANTES secretion by OLP lesional T cells. This again sets in a vicious
cycle which relates to the chronic nature of the disease.[10]
60% mast cells have been found to be degranulated in OLP compared to 20% in normal mucosa.
Mast cell degranulation releases a range of pro-inflammatory mediators such as TNF-α, chymase
and tryptase. TNF-α upregulates the expression of endothelial cell adhesion molecules (CD62E,
CD54 and CD106) in OLP, which is required for lymphocyte adhesion to the luminal surfaces of
blood vessels and subsequent extravasation and stimulates RANTES secretion from T cells.
Chymase, a mast cell protease, is a known activator of MMP-9, leading to basement membrane
disruption in OLP.[1,9]
Weak expression of transforming growth factor (TGF)-β1 has been found in OLP. TGF-β1
deficiency may predispose to autoimmune lymphocytic inflammation. The balance between
TGF-β1 and IFN-γ determines the level of immunological activity in OLP lesions. Local
overproduction of IFN-γ by CD4+ T cells in OLP lesions downregulates the immunosuppressive
effect of TGF-β1 and upregulates keratinocyte MHC class II expression and CD8+ cytotoxic Tcell activity.[1,8]

HEPATITIS C VIRUS INFECTION AND ORAL LICHEN
PLANUS
Epidemiological evidences from more than 90 controlled studies worldwide strongly suggest that
Hepatitis C Virus (HCV) may be an etiologic factor in OLP. The association seems to be
prevalent in Southern Europe, Japan and USA. However, countries with highest prevalence of
HCV report negative or nonsignificant associations suggesting that the LP–HCV association
cannot be explained on the basis of high prevalence in population alone. In OLP, HCV
replication has been reported in the epithelial cells from mucosa of LP lesions by reverse
transcription/polymerase chain reaction or in-situ hybridization; also, HCV-specific CD4 and
CD8 lymphocytes were reported in the subepithelial band. These probably suggest that HCVspecific T lymphocytes may play a role in the pathogenesis of OLP. The characteristic band like
lymphocytic infiltrate might thus be directed toward HCV infected cells. Whether HCV infected
patients have increased risk of developing OLP or patients with OLP have enhanced risk of
developing HCV infection is yet to be answered. The putative pathogenetic link between OLP
and HCV still remains controversial and needs a lot of prospective and interventional studies for
a better understanding.[11]

DIFFERENTIAL DIAGNOSIS
The diagnosis of reticular lichen planus can often be made based on the clinical findings alone.
Interlacing white striae appearing bilaterally on the posterior buccal mucosa is often
pathognomonic. Difficulties arise often when there is superimposed candidal infection which
masquerades the classic reticular pattern and in eliciting the erosive and erythematous forms of
OLP. The differential diagnosis can include cheek chewing/frictional keratosis, lichenoid
reactions, leukoplakia, lupus erythematosus, pemphigus, mucus membrane pemphigoid,
erythematous candidiasis and chronic ulcerative stomatitis. Lichenoid drug reactions are usually
unilateral in distribution, accompanied by a history of new drug intake. The most reliable method
to diagnose lichenoid drug reactions is to note if the reaction resolves after the offending drug is
withdrawn, and returns if the patient is challenged again. Dental restorative material induced
lichenoid reactions can be identified when OLP like lesions are confined to areas of the oral
mucosa in close contact or proximity to restorative materials, usually amalgam. A positive patch
test, a strong clinical correlation of proximity of a restoration and biopsy suggestive of diffuse
lymphocytic infiltrate rather than a subepithelial band favor a diagnosis of oral lichenoid
reactions. Clinically, lesions of lupus erythematosus (LE) most often resemble erosive lichen
planus but tend to be less symmetrically distributed. The keratotic striae of LE are much more
delicate and subtle than Wickham's striae and show a characteristic radiation from the central
focus. Biopsy of LE shows a characteristic perivascular infiltrate.
Erosive or atrophic types that usually affect the gingiva should be differentiated from
pemphigoid, as both may have a desquamative clinical appearance. Both pemphigus and
pemphigoid occur as solitary erythematous lesions and are not associated with any white striae.
This can aid in clinical differential diagnosis as erosive and atrophic forms of OLP usually show
concomitant reticular form. Peeling of the epithelium from the epithelium–connective tissue
junction on slight lateral pressure in nonaffected area (Nikolsky's sign) differentiates it from
erosive and erythematous forms of lichen planus. A biopsy from the perilesional tissue can
diagnose pemphigus or pemphigoid, which show intraepithelial or subepithelial split
histologically. In some cases, erythema multiforme (EM) can resemble bullous lichen planus, but
EM is more acute and generally involves the labial mucosa. Chronic ulcerative stomatitis (CUS)
is an immune-mediated disorder affecting the oral mucosa which clinically and
histopathologically resembles lichen planus. Diagnosis of CUS is based on direct
immunofluorescence studies where autoantibodies are directed against p63 in the basal and
parabasal layers of the epithelium. These lesions have to be differentiated from lichen planus
because CUS does not respond to corticosteroid therapy and has to be treated using antimalarial
drugs.[12]

RECENT CONCEPTS IN TREATMENT
Corticosteroids have been the mainstay of management of OLP; yet, other modalities like
calcineurin inhibitors, retinoids, dapsone, hydroxychloroquine, mycophenolate mofetil and
enoxaparin have contributed significantly toward treatment of the disease.Analysis of current
data on pathogenesis of the disease suggests that blocking IL-12, IFN-γ, TNF-α, RANTES, or

MMP-9 activity or upregulating TGF-β1 activity in OLP may be of therapeutic value in the
future.[1,13]

Corticosteroids
These are the most commonly used group of drugs for the treatment of OLP.[14] The rationale
behind their usage is their ability to modulate inflammation and immune response. They act by
reducing the lymphocytic exudate and stabilizing the lysosomal membrane.[15] Topical
midpotency corticosteroids such as triamcinolone acetonide, high-potent fluorinated
corticosteroids such as fluocinonide acetonide, disodium betamethasone phosphate, and more
recently, superpotent halogenated corticosteroids such as clobetasol are used based on the
severity of the lesion. The greatest disadvantage in using topical corticosteroids is their lack of
adherence to the mucosa for a sufficient length of time. Although trials were done using topical
steroids along with adhesive base, no study shows their superiority when compared to steroids
without the base (carboxymethyl cellulose).[16] However, the same study also recommends the
usage of adhesive paste used for dentures, which contains only inactive ingredients as a vehicle
to carry the topical application. This has shown excellent bioadhesive properties, due to its high
molecular weight (above 100,000) and the flexibility of the polymeric chain. Small and
accessible erosive lesions located on the gingiva and palate can be treated by the use of an
adherent paste in a made-to-measure tray (custom tray), which allows for accurate control over
the contact time and ensures that the entire lesional surface is exposed to the drugs.[17] Patients
with widespread forms of OLP are prescribed high-potent and superpotent corticosteroids
mouthwashes and intralesional injections. Long-term use of topical steroid can lead to the
development of secondary candidiasis which necessitates antifungal therapy.[15] The potential
tachyphylaxis and adrenal insufficiency is high when using superpotent steroids like clobetaso l,
especially when used for a longer period of time. Systemic corticosteroids are reserved for
recalcitrant erosive or erythematous LP where topical approaches have failed. Systemic
prednisolone is the drug of choice, but should be used at the lowest possible dosage for the
shortest duration (40–80 mg for 5–7 days).[14]

OTHER IMMUNOSUPPRESSANTS AND
IMMUNOMODULATORY AGENTS
Calcineurin inhibitors
Calcineurin is a protein phosphatase which is involved in the activation of transcription of IL-2,
which stimulates the growth and differentiation of T-cell response.[18] In immunosuppressive
therapy, calcineurin is inhibited by cyclosporine, tacrolimus and pimecrolimus. These drugs are
called calcineurin inhibitors.
Cyclosporine
Cyclosporine, a calcineurin inhibitor, is an immunosuppressant used widely in post-allogenic
organ transplant to reduce the activity of patient's immune system. This selectively suppresses Tcell activity, the main reason for transplant rejection, and hence enhances the uptake of the

foreign organ. Cyclosporine binds to the cytosolic protein cyclophilin of immunocompetent
lymphocytes, especially T-lymphocytes. This complex of cylosporine and cyclophilin inhibits
calcineurin, which under normal circumstances induces the transcription of IL-2. They also
inhibit lymphokine production and IL release, leading to a reduced function of effector T-cells.
Cyclosporine is used as a mouth rinse or topically with adhesive bases in OLP. However, the
solution is prohibitively expensive and should be reserved for highly recalcitrant cases of OLP.
Systemic absorption is very low.[14] It is known to cause dose-related gum hyperplasia which
reduces when the drug is withdrawn.
Tacrolimus
Tacrolimus, also a calcineurin inhibitor, is a steroid-free topical immunosuppressive agent
approved for the treatment of atopic dermatitis. It is 10–100 times as potent as cyclosporine and
has greater percutaneous absorption than cyclosporine. It has been successfully used in
recalcitrant OLP cases. This substance is produced by Streptomyces tsukubaensis and belongs to
the macrolide family. The immunosuppressive action of tacrolimus is similar to that of
cyclosporine, although it has a greater capacity to penetrate the mucosa. It inhibits the first phase
of T-cell activation, inhibiting the phosphatase activity of calcineurin. Burning sensation is the
commonest side effect observed; relapses of OLP after cessation have also been observed. The
US Food and Drug Administration has recently issued a potential cancer risk from the prolonged
use of tacrolimus and has recommended its use for short periods of time and not continuously.
[14,18]
Pimecrolimus
Pimecrolimus inhibits T-cell activation by inhibiting the synthesis and release of cytokines from
T cells. Pimecrolimus also prevents the release of inflammatory cytokines and mediators from
mast cells. 1% topical cream of pimecrolimus has been successfully used as treatment for OLP.
Pimecrolimus has significant anti-inflammatory activity and immunomodulatory capabilities
with low systemic immunosuppressive potential.[19,20]

Retinoids
Topical retinoids such as tretinoin, isotretinoin and fenretinide, with their immunomodulating
properties, have been reported to be effective in OLP. Reversal of white striae can be achieved
with topical retinoids, although effects may only be temporary. Systemic retinoids have been
used in cases of severe lichen planus with variable degree of success. The positive effects of
retinoids should be weighed against their rather significant side effects like cheilitis, elevation of
serum liver enzymes and triglyceride levels and teratogenicity.[8,21]

Dapsone
As an antibacterial agent, dapsone inhibits bacterial synthesis of dihydrofolic acid and hence is
used in the treatment of leprosy. When used for the treatment of skin diseases, it probably acts as
an anti-inflammatory agent by inhibiting the release of chemotactic factors for mast cells.[22]
The most common untoward effect of dapsone is hemolysis of varying degree, which is dose

related and develops in almost every individual administered 200–300 mg of oral dapsone daily.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency can increase the risk of hemolytic
anemia or methemoglobinemia in patients receiving dapsone. Screening for G6PD deficiency is
required before prescribing dapsone. Hypersensitivity reaction to dapsone called Dapsone
reaction is frequent in patients receiving multiple drug therapy. The symptoms of rash, fever and
jaundice generally occur within the first 6 weeks of therapy and can be ameliorated by
corticosteroid therapy.[23]

Mycophenolates
Originally used to treat psoriasis, mycophenolic acid (now reformulated as mycophenolate
mofetil) has been reintroduced in dermatological medicine. Being a very well-tolerated
immunosuppressive drug used in organ transplant, it has been successfully used to treat severe
cases of OLP. Mycophenolates are quite expensive and effective with long-term usage.[24]

Low-dose, low molecular weight heparin (enoxaparin)
Low-dose heparin devoid of anticoagulant properties inhibits T lymphocyte heparanase activity
which is crucial in T-cell migration to target tissues. This promises to be a simple, effective and
safe treatment for OLP when injected subcutaneously as it has no side effects.[25]

Efalizumab
It is a recombinant humanized monoclonal antibody which is used as an immunosuppressant in
the treatment of psoriasis. Efalizumab, a monoclonal antibody to CD11a, binds to this adhesion
molecule and causes improvement in OLP by decreased activation and trafficking of T
lymphocytes. In vitro studies of mononuclear cells in OLP have demonstrated a decrease of 60%
in migration by peripheral blood mononuclear cells after pretreatment with anti-CD11a
antibodies. It is administered once a week as a subcutaneous injection. It is currently an approved
drug for the treatment of plaque psoriasis.[26] Figure 1 gives a schematic representation of the
probable sites of action of drugs based on their property in OLP.

NON-PHARMACOLOGICAL MODALITIES
PUVA therapy
This non-pharmacologic approach uses photochemotherapy with 8-methoxypsoralen and long
wave ultraviolet light (PUVA). Psoralens are compounds found in many plants, which make the
skin temporarily sensitive to UV radiation. Methoxypsoralen is given orally, followed by
administration of 2 hours of UV radiation intraorally in the affected sites. It has been
successfully used in the treatment of severe cases of OLP.[27] Two major disadvantages of
PUVA therapy include the adverse effects of nausea and dizziness secondary to psoralen and 24hour photosensitivity when this medicine is taken orally. Also, dosimetry can be difficult within
the complicated geometry of the mouth, because PUVA is usually administered on skin over
large, open surfaces.[28]

Photodynamic therapy
Photodynamic therapy (PDT) is a technique that uses a photosensitizing compound like
methylene blue, activated at a specific wavelength of laser light, to destroy the targeted cell via
strong oxidizers, which cause cellular damage, membrane lysis, and protein inactivation. PDT
has been used with relative success in the field of oncology, notably in head and neck tumors.
PDT is found to have immunomodulatory effects and may induce apoptosis in the
hyperproliferating inflammatory cells which are present in psoriasis and lichen planus. This may
reverse the hyperproliferation and inflammation of lichen planus.[29]

Laser therapy
In patients who are suffering from painful erosive OLP and are unresponsive to even topical
superpotent corticosteroids, surgical management using cryosurgery and different types of laser
have also been tried. A 980-nm Diode laser,[30] CO2 laser evaporation,[31] biostimulation with a
pulsed diode laser using 904-nm pulsed infrared rays[32] and low-dose excimer 308-nm laser
with UV-B rays have been tried.[28] All types of laser destroy the superficial epithelium
containing the target keratinocytes by protein denaturation. A deeper penetrating beam like the
diode laser destroys the underlying connective tissue with the inflammatory component along the
epithelium. The few studies documented show a lot of promise, but their effectiveness is yet to
be proven.
No therapy for OLP is completely curative; the goal of treatment for symptomatic patients is
palliation. The following [Figure 2] simple systematic protocol will aid in effective treatment.
Relief can be achieved in a majority of cases through topical application of corticosteroids, with
or without the combination of other immunomodulators. Very rarely does the condition
necessitate systemic therapy. Laser therapy and other recent modalities are tried as the final
remedy.

CONCLUSION
OLP is a very common oral dermatosis and one of the most frequent mucosal pathosis
encountered by dental practitioners. It is imperative that the lesion is identified precisely and
proper treatment be administered at the earliest. A proper understanding of the pathogenesis of
the disease becomes important for providing the right treatment.

Clinical Feature
Diagnosis and Management of Oral Lichen Planus
Complex and incurable, OLP demands careful, continuous attention
Nelson L. Rhodus, D.M.D., M.P.H.,*

Sandra Myers, D.D.S., M.S.,** and
Shanti Kaimal, B.D.S., M.D.S.***

Introduction
It was Erasmus Wilson who coined the term "lichen planus" in 1869. He considered
this to be the same disease as "leichen ruber", previously described by
Hebra.Wickham noted the punctuations and striae atop the lesions that currently
bear his name.2 Today, lichen planus, including the cutaneous form and oral lichen
planus (OLP), is recognized as a chronic mucocutaneous
inflammatory condition of the stratified squamous epithelia.
Oral lichen planus (OLP) is a poorly defined and misunderstood chronic
inflammatory condition involving the oral mucosal tissues. The condition is most
often seen in middle-aged patients, and affects more women than men.3-4
Children are only rarely affected. 5 The etiology of lichen planus is most likely of
multifactorial origin.6
OLP is believed to be a T-cell mediated autoimmune disorder, although the initial
event in OLP lesion formation and the factors that determine OLP susceptibility are
unknown.4 Others believe that OLP has a genetic predisposition and is initiated by
a variety of factors, including emotional stress and hypersensitivity to drugs,
dental materials, or food.5-8 Some of the potential contributors to OLP and its
periodic exacerbations are listed in Table I.

Clinical Presentation
The clinical presentation of OLP is variable, and it may present as any one of the
following clinical forms: atrophic, bullous, erosive, papular, plaque-like, or reticular,
with the reticular form the most common.3-4
Lesions of OLP are typically bilateral. Any location in the oral cavity may be
involved, with the most common site being the posterior buccal mucosa.7 Other
common locations cited for OLP include: tongue, gingiva, retromolar/ tuberosity
area, vestibule, palate, floor of the mouth, and lip.8 Although OLP lesions generally
have a distinct clinical morphology, they may also present a confusing array of
patterns and forms. At least six clinical appearances have been described, and it is
not uncommon to have more than one form in any individual patient. It is also not
uncommon for the lesions to change not only in character and severity but also in
intraoral anatomic locations.

Forms of Lichen Planus

Recticular form This is the most common type. It consists of slightly raised slender
whitish lines in an interlocking lace-like pattern ("Honiton lace" or "Wickham's
striae") or in an annular arrangement. This lace-like network is often interspersed
with papules or rings (Figure 1).

Papular form Minute white papules may be seen. These gradually enlarge and
coalesce to form either a reticular, annular, or plaque pattern.
Plaque-like form The plaque form may be difficult to distinguish from leukoplakia,
but in OLP there is usually no change in the flexibility of the affected mucosa.
Another distinguishing feature may be the presence of a reticular periphery.
Atrophic form Atrophic OLP presents as a diffuse red or erythroplakic lesion.
Erosive form Erosive OLP often presents an amalgamation of erythematous and
ulcerative areas surrounded by keratotic striae. Gingival involvement with this form
produces desquamative
gingivitis (Figure 2).

Bullous form This form of OLP is quite rare. The intraoral bullae rupture soon after
they appear, resulting in the classic appearance of erosive OLP.
Significant pain and discomfort accompany the atrophic, erosive, and bullous
forms.9 Typically there is a cycle of waxing and waning with respect to the
symptoms. The cycles may vary, but usually occur about every three to four
weeks.9 Cutaneous lesions occasionally accompany OLP in about 30% of cases.10
The characteristic cutaneous lesion is a flat-topped, erythematous or
violaceous pruritic papule typically involving the flexor surfaces of the legs and
arms, especially the wrists. The papules occur either as isolated lesions or in
aggregate patterns and may show a fine transparent superficial scale. Wickham's
striae may be present on many papules. Hyperpigmentation may be a sequela,
and is often quite marked but temporary. The nail beds may also be affected,
resulting in ridging, thinning, and subungual hyperkeratosis. Scalp involvement, if
untreated, can lead to scarring and permanent hair loss.10

Diagnosis
Lesions of OLP often present a diagnostic dilemma. In addition to the patterns and
forms enumerated above, a number of lesions can simulate OLP and are
designated as "lichenoid".9 Oral lichenoid lesions can follow the administration of a
systemic drug (non-steroidal anti-inflammatory drugs, beta blockers etc.),
placement of a dental restoration, or provision for a denture.10-11 Flavorings,

especially cinnamates in toothpaste, may also trigger lichenoid contact sensitivity
reactions12-13 (Table I).
Emotional stress has been considered to be a strong contributing factor by many
investigators, especially for the exacerbation phases of OLP.2-11 Most of these
lesions are unilateral and usually regress after removal of the causative (or
precipitating) factor. In general, bilateral lesion distribution is a key clinical
diagnostic feature of OLP, while unilateral distribution is a detractor rendering true
OLP less likely.3, 13-14
Many of the clinical descriptions provided by clinicians contain generic terminology
such as white/whitish, red and white, hyperkeratosis, and leukoplakia. These terms
may describe lesions other than OLP, ranging from chronic cheek chewing to
tobacco-pouch keratosis and verrucous carcinoma. Some clinicians, on the other
hand, support their provisional clinical diagnosis by
providing definitive descriptions, such as striae of Wickham, and specifying a
location for the oral lesions. The clinical appearance and location, in combination
with medical and dental findings,are valuable clues for clinicians formulating and
justifying provisional and differential clinical diagnoses. They are also valuable
considerations for pathologists in rendering definitive final diagnoses.
Approximately 30-50% of patients with OLP also have concomitant skin lesions.
The presence of these characteristic cutaneous lesions can also aid in the
diagnosis of OLP.
The diagnosis of OLP appears to have been extended by the use of modifying
terminology to include lesions that have less than definitive features. The use of
modifiers such as possible, probable, suggestive of, and consistent with OLP in
definitive final diagnoses when the findings are less than classic may be
misleading to clinicians formulating treatment options and follow-up care.
Therefore the use of such confusing terminology should be restricted.8-9
In a recent study , it was reported that the ratio of females to males diagnosed
with OLP was approximately two to one over a ten-year period, and the mean age
for females increased by 5.2 years while the mean age for males decreased by
12.2 years. The percentage of all oral lesions biopsied over the time period which
were diagnosed as OLP increased from 1.6% to 4.1%. However, the percentage of
definitively diagnosed OLP lesions decreased from 100% to 42% over the same
time period. These results indicate the difficulty with which OLP is diagnosed by
histopathology alone. It is very important to include complete clinical information
in the diagnosis of OLP.9

Histopathology
The histopathological features of OLP have been well established.14-15 The
requisite features are liquefaction degeneration of the basal cells and a band-like
infiltrate of lymphocytes within the lamina propria that intimately intermingles with
the basal cell region of the surface epithelium. Additional features are the "sawtoothed" rete pegs, hyperkeratosis or parakeratosis, separation of surface
epithelium from the underlying connective tissue, and the formation of "Civatte
bodies"14 (Figure 3). These features are often present but are not a prerequisite for
diagnosis.
The appearance of the classic histologic features makes the diagnosis of OLP fairly
straightforward. It is only when the findings are variable and nonspecific that the
diagnostic process is fraught with errors. The use of qualifying and disqualifying
factors to rule in or rule out identifiable causes can substantially narrow the clinical
and histopathologic diagnosis of lesions considered "true" OLP.9
Historically, both the histologic and clinical diagnoses of OLP have been enigmas.
Histologic diagnostic criteria to separate OLP from lichenoid lesions and lichenoid
dysplasia have been elucidated by several investigators 13-14 (Figure 3).

Relationship With Squamous Cell Carcinoma
Case studies16-18 have shown that some patients with a diagnosis of OLP also
develop squamous cell carcinoma (SCC) within or adjacent to lichenoid lesions
(Figure 4). Some investigators19-21 have attempted to demonstrate that OLP has
premalignant potential and can progress to SCC. However, the question of whether
the premalignant epithelial dysplasia or the OLP came first remains controversial. A
significant problem in establishing a relationship between OLP and the
development of SCC is the difficulty in differentiating histologically between the
variable findings in OLP and those of dysplastic lesions with lichenoid features.1314 In an effort to investigate these as two distinct and separate histopathologic
entities, researchers are examining p53 a protein product of a tumor-suppressor
gene involved in DNA repair and cell cycle as well as other arrest molecular
biomarkers (Figure 3).22-24

Treatment

No known cure exists for oral lichen planus. The treatment modalities in OLP are
still empirical. The rationale for treatment is to provide oral comfort for the patient
if the lesions are symptomatic, to improve function (eating, speaking, sleeping,
wearing dental prostheses etc.), as well as to prevent or prolong the frequency and
severity of exacerbations. Systemic and local relief with anti-inflammatory and
immunosuppressant agents is often indicated. In some cases concomitant topical
anesthetics, analgesics, and antifungal agents are also indicated. Identification of
any precipitating factors including diet, dental materials, dental hygiene products,
or medication (lichenoid drug reaction) (Table I) should be undertaken to ensure
against a hypersensitivity reaction or exacerbation. Treatment or prevention of a
secondary fungal infection with a systemic antifungal agent also should be
considered in most cases.
In general, the quiescent, asymptomatic reticular and plaque forms do not warrant
pharmacological intervention, while the erythematous and erosive forms are
associated with a high degree of morbidity. Regardless of clinical type or
presentation, lesions of OLP undergo periods of exacerbation and quiescence.
Treatment is therefore aimed at reducing the severity and length of these episodic
outbreaks.
Maintenance of oral hygiene with a non-abrasive dentifrice and avoidance of
alcohol-containing mouthwashes is important since these have been observed to
reduce severity of the symptoms.

Potential for Malignancy and Periodic Biopsies
Any chronic and/or refractory lesion should be considered for a biopsy, first to
establish a diagnosis and subsequently to rule out malignancy. Periodic biopsies
are indicated for persistent lesions as there is a potential for malignant
transformation. The reported incidence of malignant transformation is
approximately 2-5%. The mean length of time for OLP to transform to squamous
cell carcinoma is 7.2 years.4,15,18,25 These figures indicate the need for longterm, appropriate follow-up and monitoring.

Topical Steroids
Stated again, there is no cure for OLP. Therapy should be individually tailored to
the specific patient and is aimed at reduction of inflammation. Therapies with
steroids and immunomodulating drugs are presented to inform the clinician that
such modalities are available. There are several of these agents, and there is no
single recommended therapy. Because of the potential for side effects, close
collaboration with the patient's physician is recommended when these medications
are prescribed. These modalities may be beyond the scope of clinical experience of

general dentists, and referral to a specialist in oral medicine, a dentist with training
and experience in this area, or to an appropriate physician may be necessary.26
Prolonged use of topical steroids (for a period of greater than two weeks
continuous use) may result in mucosal atrophy and secondary candidiasis, and
may increase the potential of systemic absorption. The concomitant prescribing of
antifungal therapy along with the topical steroids may be necessary. Therapy with
topical steroids, once the lichen planus is under control, should be tapered to
alternate-day (or less) therapy depending on control of the disease and the
tendency to recur. A usual course of steroid therapy should not exceed 10-14 days,
with an interim period approximately the same before re-instituting the steroid
therapy.
Steroid therapy may include any of the following.
Potent: Dexamethasone (Decadron) oral rinse, 0.5 mg/5 ml
Fluocinonide (Lidex) gel, 0.05%
Intermediate: Betamethasone valerate (Valisone) ointment 0.1%
Triamcinolone acetonide (Kenalog) ointment 0.1%
Low: Hydrocortisone gel or ointment, 1.0%
Ultra-potent: Clobetasol propionate (Temovate) ointment, 0.05%
Halobetasol propionate (Ultravate) ointment, 0.05%
Examples of prescriptions for OLP would be:
Ç Fluocinonide (Lidex) gel 0.05%
Ç Disp: 30 gm tube
Ç Sig: Coat the lesion with a thin film after each meal and at bedtime.
Or Ç Dexamethasone (Decadron) elixir 0.5 ma/5 ml
Ç Disp: 100 ml
Ç Sig: Rinse with one teaspoonful for two minutes qid and spit out. Discontinue
when lesions become asymptomatic.

Maintenance
In periods of remission and quiescence, OLP may be kept under control and the
symptomatic exacerbation phase reduced in frequency by several interventions.
First, elimination or avoidance of precipitating or perpetuating factors such as SLScontaining dentifrices, spicy or acidic foods,tissue trauma, and xerostomia-inducing
agents (Table I). A "magic mouthwash" containing benadryl, kaopectate (or
carafate), and milk of magnesia as a base to which nystatin and/or lidocaine may
be added (depending upon the clinical indications) is quite effective as a therapy
for mildly symptomatic cases or as maintenance therapy.

Oral candidiasis may result from topical steroid therapy. The oral cavity should be
monitored for emergence of fungal infection on patients who are placed on steroid
therapy. Most often oral candidiasis presents clinically as macular erythema,
angular cheilosis, or pseudomembranous white plaques which can be scraped off
the mucosa. However, significant candidiasis may be present with few clinical
signs. Prophylactic antifungal therapy should be initiated in patients with a history
of fungal infection and/or immunosuppressed patients and/or those with prior
steroid administration.26,27

Phased and Combination Therapies
Due to the phasic nature of OLP alternating between symptomatic exacerbations
and remissions, often a phased sequence of therapy is warranted and
effective.26,27 In these cases, a more potent regimen of topical corticosteroid for a
week or two followed by a second phase regimen of lesser potent topical
corticosteroids will provide effective therapy. Additionally, often during periods of
acute exacerbation, combinations of more than one topical corticosteroid may be
effective
‹ for example, first the dexamethasone oral rinse followed by application of
fluocinonide or triamcinolone ointment. There are many combinations which may
be utilized, depending upon the individual clinical scenario.
Obviously, proper diagnosis and recognition of the nature of the OLP in the
individual patient along with detailed patient information and self-therapy
instruction are essential.
Systemic steroids and immunosuppressants prescribed for more severe cases
would include:
Ç Dexamethasone (Decadron) elixir 0.5 mg/5 ml
Ç Disp: 320 ml
Ç Sig: 1. For 3 days, rinse with 1 tablespoonful (15 ml) qid and swallow. Then 2. For
3 days, rinse with teaspoonful (5 ml) qid and swallow. Then 3. For 3 days, rinse
with 1 teaspoonful (5 ml) qid and swallow every other time. Then 4. Rinse with 1
teaspoonful (5 ml) qid and expectorate.
Or ‹
Ç Prednisone tablets 10 mg
Ç Disp: 26 tablets
Ç Sig: Take 4 tablets in the morning for 5 days, then decrease by 1 tablet on each
successive day.
Or Ç Prednisone tablets 5 mg
Ç Disp: 40 tablets
Ç Sig: Take 5 tablets in the morning for 5 days, then 5 tablets in the morning every

other day until
gone.
If oral discomfort recurs, the patient should return to the clinician for reevaluation.
Many studies suggest that oral lichen planus has an intrinsic property predisposing
to malignant transformation. However, the etiology is complex, with interaction
among factors including infectious agents, genetic variables, environmental
influences, and lifestyle elements. Prospective studies have demonstrated that
lichen planus patients have a slightly increased risk to develop oral squamous cell
carcinoma. All patients exhibiting lichen planus intraorally, particularly those who
have had the ulcerative form, should receive periodic follow-up.
Therapy with medications such as systemic steroids, immunosuppressants, and
immunomodulators is presented to inform the clinician that such modalities have
been reported effective for patients suffering from ulcerative lichen planus.
Medications such as azathioprine, mycophenolate mofetil, tacrolimus hydroxychloroquinesulfate, acitretin, and cyclosporine-A are used to treat patients with
severe persistent ulcerative lichen planus but should not be routinely used
because of the potential for side effects. Close collaboration with the patient's
physician is recommended when these medications are prescribed.

Summary
Oral lichen planus is a complex and poorly understood clinical condition which
cannot be cured. A definitive diagnosis and careful, conscientious follow-up are
imperative. Symptoms and complications are common and challenging but may be
managed with a variety of therapies including orally administered and systemic
medications as well as lifestyle alterations and reduction of precipitating factors.
References
1. Wilson, E.: On lichen planus. J Cutan Med Dis Skin 3: 117-132, 1869.
2. Wickham, L.F.: Sur un signe pathognomonique delichen du Wilson (lichen plan)
stries et punctuations grisatres.Ann Dermatol Syph 6: 17-20, 1895.
3. Vincent, S.D., Fotos, P.G., Baker, K.A. et al: Oral lichen planus: the clinical,
historical, and therapeutic features of 100 cases. Oral Surg Oral Med Oral Pathol
70: 165-171, 1990.
4. Lozada-Nur, F., and Miranda, C.: Oral lichen planus: epidemiology, clinical
characteristics, and associated diseases. Sem Cutan Med Surg 16: 273-277, 1997.
5. Jungell, P.: Oral lichen planus: a review. Int J Oral Maxillofac Surg 20(3): 129-135,
1991.
6. Scully, C., Beyli, M., Ferreiro, M.C., Ficarra, G., Griffiths, M. et al: Update on oral
lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med 9(1): 86122, 1998.

7. Sugerman, P.B., Savage, N.W., Walsh, L.J., Zhao, Z.Z., Zhou, X.J. et al: The
pathogenesis of oral lichen planus. Crit Rev Oral Biol Med 13(4): 350-365, 2002.
8. Brown, R.S., Bottomley,W.K., Puente, E., and Lavigne, G.L.:A retrospective
evaluation of 193 patients with oral lichen planus. J Oral Pathol Med 22(5): 69-72,
1993.
9. Myers, S.L., Rhodus, N.L., Parsons, H.M., Hodges, J.S., and Kaimal, S.: A
retrospective survey of oral lichenoid lesions: revisiting the diagnostic process for
oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93: 676-681,
2002.
10. Scully, C., and El-Kom, M.: Lichen planus: review and update on pathogenesis. J
Oral Pathol 14: 431-458, 1985.
11. Sugerman, P.B., Savage, N.W., Zhou, X., Walsh, L.J., and Bigby, M.: Oral lichen
planus. Clin Dermatol 18: 533-539, 2000.
12. Porter, S.R., and Scully, C.: Adverse drug reactions in the mouth. Clin Dermatol
18: 525-532, 2000.
13. Yiannis, J.A., el-Azhary, R.A., Hand, J.H., Pakzad, S.Y., and Rogers III, R.S.:
Relevant contact sensitivities in patients with the diagnosis of oral lichen planus. J
Am Acad Dermatol 42: 177-182, 2000.
14. Eisenberg, E.: Clinicopathologic patterns of oral lichenoid lesions. In Oral &
Maxillofacial Surgery Clinics of North America. Philadelphia:WB Saunders, 1994,
pages 445-463.
15. Krutchkoff,D.J., and Eisenberg, E.: Lichenoid dysplasia: a distinct
histopathologic entity. Oral Surg Oral Med Oral Pathol 30: 308-315, 1985.
16. Camisa, C., Hamaty, F.G., and Gay, J.D.: Squamous cell carcinoma of the
tongue arising in lichen planus: a case report and review of the literature. Cutis 62:
175-178, 1998.
17. Duffey, D.C., Eversole, L.R., and Abemayor, E.: Oral lichen planus and its
association with squamous cell carcinoma: an update on pathogenesis and
treatment implications. Laryngoscope 106: 357-362, 1996.
18. Kaz, R.W., Brahim, J.S., and Travis,W.D.: Oral squamous cell carcinoma arising in
a patient with long-standing lichen planus. Oral Surg Oral Med Oral Pathol 70: 282285, 1990.
19. Barnard, N.A., Scully, C., Eveson, J.W. et al: Oral cancer development in
patients with oral lichen planus. J Oral Pathol Med 22: 421-424, 1993.
20. Lo Muzio, L., Mignogna, M.D., Favia, G. et al:The possible association between
oral lichen planus and oral squamous cell carcinoma: a clinical evaluation on 14
cases and a review of the literature. Oral Oncol 34: 239-246, 1998.
21. Markopoulos,A.K.,Antoniades,D., Papanayotou, P. et al: Malignant potential of
oral lichen planus: a follow-up study of 326 patients. Oral Oncol 33: 263-269,
1997.
22. Girod, S.C., Krueger, G., and Pape, H.D.: p53 and Ki 67 expression in
preneoplastic and neoplastic lesions of the oral mucosa. Int J Oral Maxillofac
Surgery 22: 285-288, 1993.

23. Girod, S.C., Pfeiffer, P., and Pape, H.D.: Proliferative activity and loss of function
of tumour suppressor genes as 'biomarkers' in diagnosis and prognosis of benign
and preneoplastic oral lesions and oral squamous cell carcinoma. Br J Oral
Maxillofac Surg 36: 252-260, 1998.
24. Schifter, M., Jones,A.M., and Walker,D.M.: Epithelial p53 gene expression and
mutational analysis, combined with growth fraction assessment, in oral lichen
planus. J Oral Pathol Med 27: 318-324, 1998.
25. Onofre, M.A., Sposto, M.R., Navarro, C.M. et al: Potentially malignant epithelial
oral lesions: discrepancies between clinical and histological diagnosis. Oral Dis 3:
148-152, 1997.
26. Clinician's Guide to the Treatment of Common Oral Conditions, Fourth Edition,
by Rosenberg, S.W., Arm, R.N., Bottomly, W.K., Rhodus, N.L. et al. New York, New
York: American Academy of Oral Medicine, Inc., 1997.
27. Rhodus, N.L.: Clinical observations from approximately 300 patients, 2002.

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