oral lichen planus

1. ORAL LICHEN
PLANUS
PRESENTED BY-
PRIYA GIMEKAR ( I ST YEAR PG )
GUIDED BY-
PROF. DR. MAHENDRA PATAIT
DR.KEDAR SARAF

2. DEFINITION
Oral Lichen planus (OLP) is a chronic
mucocutaneous disorder of the stratified squamous
epithelium that affects oral and genital mucous
membranes, skin, nails, and scalp.

3.  Oral lichen planus (OLP) is derived from the Greek word
“leichen” means tree moss and Latin word “planus” means
flat.
 It was first presented by the English physician Erasmus
Wilson in 1866.He considered this to be the same disease as
“lichen ruber,” previously described by Hebra.
 In 1895, Wickham noted the characteristic reticulate white
lines on the surface, today recognized as Wickham striae.
 Darier is credited with the first formal description of the
histopathological changes associated with OLP.

4. The World Health Organization classifies oral
precancerous/potentially malignant disorders into 2 general
groups, as follows:
A precancerous lesion is “a morphologically altered tissue in
which oral cancer is more likely to occur than its apparently
normal counterpart.”
These precancerous lesions include
 leukoplakia,
 erythroplakia, and
 the palatal lesions of reverse smokers.

5. A precancerous condition is “a generalized state
associated with significantly increased risk of cancer.”
The precancerous conditions include
 submucous fibrosis,
 Oral lichen planus,
 epidermolysis bullosa, and
 discoid lupus erythematous.
OLP has been classified as premalignant condition by
WHO in 1997.

6.  The Indian subcontinent has a particularly high incidence of
disease, estimated to affect 0.5% to 2.0% of the general
population.
 The relative risk is 3.7% in people with mixed oral habits,
lowest (0.3%) in non-users of tobacco and highest (13.7%)
among those who smoked and chewed tobacco.
Epidemiology

7.  This disease has most often been reported in middle-aged
patients with 30-60 years of age and is more common in
females than in males.
 According to some literature white individuals are five and
a half time more likely to develop this disease compared to
other races, occurs more frequently than the cutaneous
form and tends to be more persistent and more resistant to
treatment.

8. ETIOLOGY
 Genetic background
 Dental materials
 Drugs
 Infectious agents
 Autoimmunity
 Bowel diseases
 Food allergies
Although the exact etiology of this disease is still
unknown, but some factors are associated with it. These
are as follows –
 Stress
 Habits
 Trauma
 Diabetes & hypertension
 Malignant neoplasms
 Miscellaneous
associations

9. Genetic background :
An association has been observed with HLA-A3, A11, A26,
A28, B3,B5, B7, B8, DR1, and DRW9.
Dental materials :
Triggering elements for OLP, including silver amalgam, gold,
cobalt, palladium, chromium and non-metals such as epoxy
resins (composite) and prolonged use of denture wear.
Drugs :
Triggered by systemic drugs including NSAIDs, beta blockers,
sulfonylureas, some angiotensin-converting enzyme (ACE)
inhibitors, and some antimalarials, contact allergens including
toothpaste flavorings, especially cinnamates.

10. Infectious agents :
OLP has been found to be associated with various viral
agents such as human papilloma virus (HPV), Epstein Barr
virus (EBV), human herpes virus 6(HHV-6) and human
immunodeficiency virus (HIV).Epidemiological evidences
from various studies worldwide strongly suggest that
hepatitis C virus (HCV) may be an etiologic factor in OLP.
Autoimmunity :
OLP may occasionally be associated with autoimmune
disorders such as primary biliary cirrhosis,chronic active
hepatitis, ulcerative colitis, myasthenia gravis, and
thymoma.

11. Bowel diseases :
It is described concomitant with OLP include coeliac
disease, ulcerative colitis & Crohn's disease.
Food allergies :
Some of food additives such as cinnamon aldehyde
have been found to be associated with OLP.
Stress :
One of the factors responsible for the development
of OLP is anxiety and stress. Some of the studies in
literature reveal the role of the psychological stress in the
etiology of OLP.
Habits :
Cigarette smoking has been suggested to be an
etiological factor in some Indian communities.

12. Trauma :
It may be the mechanism by which other etiological
factors exert their effects.
Diabetes & hypertension :
Both diabetes mellitus (DM) and high blood pressure are
associated with OLP.
Malignant neoplasms :
OLP has been observed on the skin and/or mucosae of
patients affected by a range of different neoplasms such as with
breast cancer and metastatic adenocarcinoma.
Miscellaneous associations :
OLP has occasionally been associated with other
conditions, including psoriasis, lichen sclerosis, urolithiasis,
agents used to treat gall stones, Turner's syndrome.

13.  Current data suggest that oral lichen planus is a T-cell–
mediated autoimmune disease in which autocytotoxic CD8+
T cells trigger apoptosis of oral epithelial cells.
 The dense sub-epithelial mononuclear infiltrate in oral lichen
planus is composed of T cells and macrophages, and there
are increased numbers of intra-epithelial T cells.
 Most T cells in the epithelium and adjacent to the damaged
basal keratinocytes are activated CD8+ lymphocytes.
PATHOGENESIS

14.  Therefore, early in the formation of oral lichen planus
lesions, CD8+ T cells may recognize an antigen
associated with the major histocompatibility complex
(MHC) class I on keratinocytes.
 After antigen recognition and activation, CD8+ cytotoxic T
cells may trigger keratinocyte apoptosis.
 Activated CD8+ T cells (and possibly keratinocytes) may
release cytokines that attract additional lymphocytes into
the developing lesion.

16.  The matrix metalloproteinase (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
BM disruption.
 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.
 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.

18. CLINICAL FEATURES
 Cutaneous lesions may be encountered in approximately
15% of patients with OLP.
 Its consist of pruritic papules that are flat topped & have
predilection for the flexor surfaces of arms & legs.
 The papules may be discrete or coalesce to form plaques.
 The patients report relief following intense scratching of
the lesions, but trauma may aggravate the disease,
referred to as a KOEBNER PHENOMENON.

19. Cutaneous lichen planus
On the flexor side of the
fore arm.

20. Following are the clinical types of OLP :
 RETICULAR
 PAPULES
 PLAQUE –LIKE
 BULLOUS
 ERYTHEMATOUS
 ULCERATIVE
ORAL MANIFESTATIONS

21.  The different clinical manifestations of OLP is related to the
magnitude of the subepithelial inflammation.
 A mild degree of inflammation may provoke the epithelium to
produce hyperkeratosis, whereas more intense inflammation
will lead to partial or complete deterioration of the epithelium,
histopathologically perceived as atrophy, erosion or
ulceration.
 This collaborates with the fact that most erythematous &
ulcerative lesions are surrounded by white reticular or
papular structures.

22. SHKLAR & McCARTHY have reported the following
distribution of oral lesions :
 Buccal mucosa (80%)
 Tongue (65%)
 Lips (20%)
 Gingiva, floor of mouth & palate ( less than 10%).

23.  RETICULAR form of OLP is characterized by fine white
lines or striae.
 The striae may form a network but can also show
annular(circular) patterns.
 The striae often display a peripheral erythematous zone,
which reflects the subepithelial inflammation.
 Most frequently seen bilaterally in the buccal mucosa & rarely
on the mucosal side of the lips.
 Sometimes observed at the vermilion border.

24. RETICULAR form of OLP seen on lips, mucosa
of cheeks & buccal mucosa.

25.  The PAPULAR type of
OLP is usually present
in the initial phase of the
disease.
 It is clinically
characterized by small
white dots, which in
most occasions
intermingle with the
reticular form.

26.  PLAQUE-type OLP shows homogeneous well demarcated
white plaque often, but not always, surrounded by striae.
 Plaque-type lesions may clinically be very similar to
homogeneous oral leukoplakias.
 The difference between these two mucosal disorders is the
simultaneous presence of the reticular or papular structures
in the case of plaque-type OLP.
 This form is most often encountered in smokers & following
cessation, the plaque may disappear & convert into
reticular type of OLP.

27.  Some scientific reports support
that plaque-type forms of OLP
is overpresented among OLP
lesions transforming oral
squamous cell carcinomas.
 Bullous form is very unusual
but may appear as bullous
structures surrounded by
reticular network. Bullous type of OLP
seen on upper buccal
mucosa.

28. PLAQUE-type OLP on the buccal mucosa

29.  Erythematous (atrophic) OLP is characterized by a
homogeneous red area.
 When this type of OLP is present in the buccal mucosa or in
the palate, striae are frequently seen in the periphery.
 Some patients may display erythematous OLP exclusively
affecting attached gingiva.
 This form of lesion may occur without any papules or striae &
presents as desquamative gingivitis.

30. Erythematous OLP on attached gingiva

31.  ULCERATIVE type clinically presents, the fibrin coated
ulcers surrounded by an erythematous zone frequently
displaying radiating white striae.
 This appearance may reflect a gradient of the intensity of
subepithelial inflammation that is most prominent at the
center of the lesion.

32. ULCERATIVE type seen on lateral borders &
dorsum of tongue

33.  Areas of hyperparakeratosis or hyperorthokeratosis, often
with a thickening of the granular cell layer & a saw toothed
appearance to the rete pegs.
 Liquefaction degeneration or necrosis of the basal cell layer.
 An eosinophilic band may be seen just beneath the
basement membrane & represent fibrin covering the lamina
propria.
 A dense subepithelial band shaped infiltrate of lymphocytes
are seen.
HISTOPATHOLOGY

34.  Degeneration of the basal keratinocytes and disruption
of the anchoring elements of the epithelial BM and basal
keratinocytes (e.g. hemi desmosomes, filaments, fibrils)
weaken the epithelial connective tissue interface.
 As a result, histologic clefts (Max–Joseph spaces)
may form and blisters on the oral mucosa (bullous LP)
may be seen at clinical examination.

35. Saw tooth rete pegs & liquefaction degeneration in
the basal cell layer of OLP

36.  In some instances, fibrinogen and fibrin are deposited in a
linear pattern in the BM zone.
 Colloid bodies contain fibrin, IgM, C3, C4, and keratin.
 Laminin and fibronectin staining may be absent in areas of
heavy fibrin deposition and colloid body formation.
 This finding suggests BM damage in these areas.
DIRECT IMMUNOFLUORESCENCE

37.  In OLP, electron microscopy (EM) is used principally as a
research tool. The ultrastructure of the colloid bodies
suggests that they are apoptotic keratinocytes, and recent
studies using the end labeling method revealed DNA
fragmentation in these cells.
 EM shows breaks, branches, and duplications of the
epithelial BM in OLP.

38. SEROLOGY
There are no consistent serological changes
associated with OLP but some patients do present an
elevated antinuclear antibody (ANA) titer.

39.  Oral Leucoplakia
 Graft Vs host disease
(GVHD)
 Discoid lupus
erythematosus
 Lichenoid contact
reactions
 Lichenoid drug eruptions
DIFFERENTIAL DIAGNOSIS
 Cheek chewing/frictional
keratosis
 Mucus membrane
pemphigoid
 Para neoplastic pemphigus,
 Erythematous candidiasis
 Chronic ulcerative stomatitis

40.  The principal aims of current OLP therapy are the
resolution of painful symptoms, oral mucosal
lesions, the reduction of the risk of oral cancer, and
the maintenance of good oral hygiene.
 Eliminate the local exacerbating factors as
preventive measures.
MANAGEMENT

41. Up to now different therapies are described for
OLP including-
 Drug therapy,
 Psoralen with ultraviolet
light A (PUVA)
 Cryotherapy
 Laser
 Photo dynamic therapy
 Photo chemotherapy
 Surgical excision
 In general, surgery is
reserved to remove
high-risk dysplastic
areas

42. DRUG THERAPY
TOPICAL DRUGS -
 corticosteroids
 Immunosuppressives
 retinoids
 immunomodulators.
SYSTEMIC DRUGS-
 Thalidomide
 Metronidazole
 griseofulvin
 Hydroxychloroquine

43.  Topical steriods are widely used & accepted as the primary
treatment of choice.
 Steroids such as clobetasol propionate very potent than
triamcinolone acetonide.
 Topical application of cyclosporine, tacrolimus & retinoids
has been suggested as a second line therapy for OLP.
 Topical steriods preferably used as a mouthrinse & a gel.

44.  Although no systemic studies have compared different
frequencies of application, a reasonable approach may be
apply the drug 2 to 3 times a day during 3 weeks followed
by tapering during the following 9 weeks until a
maintenance dose of 2 to 3 times a week is reached.
 When topical steriods are used, a fungal infection may
emerge.A parallel treatment with antifungal drugs may be
necessary.
 If symptoms persist, steriods gels in prefabricated plastic
trays may be used for 30 mintues at each application to
increase the concentration of steriods in the gingival tissue.

45.  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.
 Corticosteroids have ability to modulate inflammation and
immune response.They act by reducing the lymphocytic
exudate and stabilizing the lysosomal membrane.
 The greatest disadvantage in using topical corticosteroids is
their lack of adherence to the mucosa for a sufficient length
of time.

46. 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.
 In immunosuppressive therapy, calcineurin is inhibited by
cyclosporine, tacrolimus and pimecrolimus.These drugs are
called calcineurin inhibitors.
 Cyclosporine, a calcineurin inhibitor, is an
immunosuppressant used widely in organ transplant to
reduce the activity of patient's immune system.

47.  This selectively suppresses T-cell 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.

48.  Cyclosporine solution should be reserved for highly
recalcitrant cases of OLP.
 Systemic absorption is very low.
 It is known to cause dose-related gum hyperplasia which
reduces when the drug is withdrawn.

49.  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.

50.  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.

51.  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.

52. 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 side effects like cheilitis, elevation of serum liver
enzymes and triglyceride levels and teratogenicity.

53. 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.
 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.

54.  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.

55. 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.

56. 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.
Efalizumab :
 It is a recombinant humanized monoclonal antibody which
is used as an immunosuppressant in the treatment of
psoriasis.

57.  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.

58. Proposed sites of action based on property of drugs
in oral lichen planus

59. 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.

60.  It has been successfully used in the treatment of
severe cases of OLP.
 Two major disadvantages of PUVA therapy include
the adverse effects of nausea and dizziness
secondary to psoralen and 24-hour 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.

61. 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.

62. 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, CO laser evaporation, biostimulation
with a pulsed diode laser using 904-nm pulsed infrared rays
and low-dose excimer 308-nm laser with UV-B rays have
been tried.
 All types of laser destroy the superficial epithelium
containing the target keratinocytes by protein denaturation.

63.  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.

65.  Malignant transformation of OLP remains a very
controversial issue.
 At least some reported cases diagnosed originally as OLP
on clinical and/or histological grounds were probably
epithelial dysplasia (lichenoid dysplasia) that progressed
subsequently to overt squamous cell carcinoma (SCC).
 The OLP lesions are consistently more persistent than the
dermal lesions and have been reported to carry a risk of
malignant transformation to oral squamous cell carcinoma
(OSCC) of 1-2% (reported range of malignant transformation
0– 12.5%).
Malignant potential

66.  Erythroplastic lesions may also occur in OLP. They develop
in approximately 1% of the patients and are sharp with
slight reddish depressions.
 In most cases, malignant transformation to carcinoma in
situ (28.5%) and in micro invasive carcinoma (30-38%) is
observed, less frequently stage I and II carcinoma.
 Oral cancer-correlated OLP predisposes to the
development of multiple primary metachronous tumors of
the oral cavity and of lymph node metastases.

67.  Metallothionein, a marker of antiapoptosis, associated with
oral lichen planus.
 It is a family of low molecular weight proteins with a affinity
for divalent metals through the thiol group of its cysteine
residues.It controls the cellular zinc ion levels.
 The proper intracellular Zn2+ level maintains the
fragmentation of DNA associated with caspase activity.
 In recent studies casp -2 has been found on epithelial cells
in cases of atrophic lichen planus which indicate the role of
intracellular stress as initiator of apoptosis.

68. References
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 Shafer, Hine, Levy. A Textbook of Oral Pathology. 4th
edition.
 Sonia Gupta and Manveen Kaur Jawanda. Oral Lichen
Planus: An Update on Etiology, Pathogenesis, Clinical
Presentation, Diagnosis and Management. Indian J
Dermatol. 2015 May-Jun; 60(3): 222–229.

69.  Sonia Gupta and Manveen Kaur Jawanda. Oral Lichen
Planus: An Update on Etiology, Pathogenesis, Clinical
Presentation, Diagnosis and Management. Indian J
Dermatol. 2015 May-Jun; 60(3): 222–229.
 N Lavanya, P Jayanthi, Umadevi K Rao, and K
Ranganathan. Oral lichen planus: An update on
pathogenesis and treatment. J Oral Maxillofac Pathol. 2011
May-Aug; 15(2): 127–132.
 R.S. Satoskar, S.D.Bhandarkar, S.S.Ainapure.
Pharmacology & Pharmacotherapeutics. 8th edition.

70. THANK
YOU