Oral lichen planus: An overview.

Lichen planus is an immunologically mediated mucocutaneous disease that is triggered by varied etiological agents. The oral lichenoid reaction is considered a variant of the disease that needs to be clearly diagnosed as a separate entity from oral lichen planus and treated. They follow a strict cause-effector relationship, protocols that suggest the differentiation. Lichen planus has varied clinical forms in the oral mucosa and cutaneously that has different prognosis. This condition also arises in association with various other systemic conditions such as hypertension, diabetes mellitus. There have been cases reported in the esophagus, larynx, scalp, nail, cutaneous areas, especially arms and wrists, trunk. There is reported malignant transformation that essentiates careful examination, treatment protocol and regular follow-up sessions. This article throws light on the disease condition of oral lichen planus and oral lichenoid reaction that is essential for the differentiation and treatment.

Lichen planus is a comparatively common, mucocutaneous disorder that is mediated immunologically. It can also be autoimmune in pathogenesis. It is chronic in occurrence, with periods of exacerbations and remission. It was first described by British Physician Wilson Erasmus in 1869. Lichens are primitive plant that consists of symbiotic algae and fungi and the word planus in Latin means flat.[1] Lichen planus has varied clinical manifestations affecting the skin, oral mucosa, nail, genital mucosa, nail, and scalp.[2] This lesion has well-established clinical features and histological features that aid in the diagnosis.

Etiology

Stress

The main etiological factor of lichen planus is stress. There are reported exacerbations of the lesion associated with anxiety and psychological stress.[345] Psychosomatization arising from prolonged emotional stress contributes greatly to initiation and clinical expression of the lesion.[36]

Systemic medications

Systemic medications such as beta blockers,[7] nonsteroidal anti-inflammatory drugs,[8] anti malarials,[9] diuretics, oral hypoglycemics,[10] penicillamine,[11] oral retroviral medications[312] are reported to initiate or exacerbate oral lichen planus and oral lichenoid reaction.

Dental materials

Dental materials such as dental amalgam,[13] resinous dental materials, composite restorations[14] are reported to cause a high incidence of oral lichenoid reaction and oral lichen planus. They are said to produce contact hypersensitivity lesions. These can be assessed by a patch test in which they present a positive result. Metals such as nickel,[15] gold salts.[16] That are released from dental cast alloys can contribute to this lesion and reaction. Of all the restorative materials, dental amalgam and nickel are reported to cause greater trigger to the initiation and progression to the condition. Oral lichenoid reactions are consequently subside with the removal of the restorative material. They can also arise as a result of galvanic reactions that arise from dissimilar materials used in cast alloys.

Chronic liver disease and hepatitis C virus

The association between chronic liver disease was first proposed by Mokni et al.[17] 1941. Controversy persists in identification of the cause in the association between these two conditions. However, geographical heterogeneity, presence of human leucocyte antigen-DR 6 (HLA-DR) allelle is postulated to be associated.[18] This association of hepatitis C virus and oral lichen planus is most prevalent in the Mediterranean regions and Japan. The interferon therapy and ribavirin therapy used in the treatment of hepatitis C viral infection are also put forward to aggravate the condition.

Genetics

Genetic basis of this disease condition plays an important role.[19] Higher frequency of HLA-A3[20] is reported to cause lichen planus.

Tobacco chewing

Zain et al. proposed the term “betel quid lichenoid lesion”[21] for the lesion developed at the area of tobacco chewing and placement in the oral mucosa. It is described as oral lichen planus like lesion. Clinically the lesion was white in color, nonelevated streaks that were nonscrapable. It had a linear, wavy or parallel presentation.[22]

Graft versus host disease

Immune system involvement is seen where the immunological effector mechanism that results in T-cell infiltration leading to the rupture of epithelial basement membrane and basal keratinocyte apoptosis.

Clinical Features

Occurs predominantly in females with a female: male ratio of 1.4:1[2] and in the age group of third to seventh decade in life. It is seen frequently in all regions of the oral mucosa, mostly noticed in buccal mucosa, gingiva and tongue. They are present bilaterally in most cases.

Classically present as six types cinically: Reticular (fine white striae cross each other in the lesion), Atrophic (areas of erythematous lesion surrounded by reticular components), papular type, bullous type, plaque type, erosive or ulcerative type. The reticular type of oral lichen planus is often asymptomatic,[23] only can be seen clinically. Ulcerative type in which erythematous areas are seen surrounded by reticular elements.

Periods of remission are seen in oral lichen planus where the symptoms and lesion appear and regress at intervals. The characteristic feature is the Wickham's striae, l[2] which is found on the surface of the lesion, formed by very fine grayish white lines. They are bilaterally symmetrical in presentation. Cutaneous presentation involves even the wrist, flexor surfaces of forearms, knees, thighs involving mainly the sacral area. The areas of shin present this condition mostly as hypertrophic plaques.

The vulvovaginal-gingival syndrome[324] is considered as a variant lichen planus. This is typically characterized by erosion and desquamation of gingiva, vagina, and vulva.

When the scalp is involved, it is called the planopilaris.[2]

Nail involvement of oral lichen planus has been reported where the finger nails showed scarring at the matrix of the nails, with subsequent obliteration of the nail plate.[25]

Formation of Pterygium

Irregular and longitudinal grooving with ridging of the nail plate

Atrophy and shedding of the nail bed

Keratosis

Hyperpigmentation subungually.

Severe pruritis that becomes intolerable is the primary symptom.

The association and occurrence of oral lichen planus along with diabetes mellitus and hypertension is termed Grinspan syndrome.[2]

Oral Manifestation

Oral lichen planus is classically present as lesion with radiating whitish gray lines thread like papules, velvety appearance. Bilateral in presentation. They can be lacy or reticular, annular, patches or strings. The occurrence and distribution of lesion in the oral mucosa is 80% in the buccal mucosa, 65% in the tongue, 20% lips, <10% seen in floor of mouth and palate. Vesicle and bulla are seen in the oral lesions of lichen planus. The disease manifests in the oral cavity several weeks before the skin lesions. About 15% of oral lichen planus patients have concurrent skin lesions.[26] The reticular form has a better prognosis as 40% of cases has spontaneous remission,[27] the erosive type being long standing and with frequent exacerbations and severe pain and complications.

Histologic Features

The three classical histological feature of oral lichen planus were put forward first by Dubreuill in 1906 and Shklar[28] later described them as:

Liquefaction degeneration of basal layer

Overlying keratinization

Lymphocytic infiltrate within the connective tissue that is dense and resembles a band.

Typical histopathological examination from the lesional biopsy reveals hyper orthokeratosis or hyperparakeratosis, with acanthosis, which is thickening of the granular layer with intercellular edema. Rete pegs characteristically are “saw tooth” in appearance. Mononuclear infiltration of the T-cells and histiocytes form a typical band like an appearance subepithelially. The intraepithelial T-cells and degenerating ketatinocytes form the colloid bodies, the homogeneous globules that are eosinophilic in nature called the civette, cytoid, hyaline bodies are seen. The characteristic feature of Max-Joseph space that is formed from the degeneration of basal keratinocytes and anchoring units disruption. They are regarded as histologic clefts. The colloid bodies ultrastructurally are apoptotic keratinocytes revealing DNA fragmentation in these cells. The basement membrane of when examined under electron microscope reveal duplications, branches, and breaks.

Etiopathogenes

Lichen planus is a T-cell mediated disease autoimmune in nature where the CD8+ T-cells trigger the apoptosis of oral epithelial cells at the basal layer.[29] Keratinocyte antigen expression and antigen unmasking are involved in the disease mechanism. It may be a self-peptide or a heat shock protein. Then subsequently T-cells migrate towards the basal keratinocytes during surveillance or chemochine mediated action. The antigen directly binds to the migrated CD8+ cells by the major histocompatibility complex-1 (MHC) on keratinocyte. Langerhans cells are increased in lesions of lichen planus and there is upregulated MHC-II expression. The CD4+ cells and interleukin-12 activate CD8+ T-cells that are involved in the apoptosis of keratinocytes through FasL mediated and tumor necrosis factor-alpha (TNF-alpha).

The vascular adhesion molecules receive the expression of the reciprocal receptors of infiltrating lymphocytes.[30] This is the cytokine-mediated lymphocyte that contributes to the homing mechanism. Matrix metallo protease 9 are majorly involved in the tissue matrix protein degradation.

The chronic nature of the disease is contributed by the Regulated on Activation, Normal T-cell expressed and secreted[31] that is, a member of “CC chemochine family”. This greatly recruits the mast cells and lymphocytes that results in degranulation, releasing chymase and TNF-alpha.

The heat shock proteins[32] are also upregulated by the lesional keratinocytes of oral lichen planus. Inflammation that exists prior to the disease condition can contribute to the expression of heat shock protein.

Malignant Transformation

The follow-up studies of oral lichen planus reveals the malignant transformation of this condition to be up to 5.3%. The highest rate of malignant transformation has been noted in erythematous and erosive type. The chance of malignant transformation drops if initial dysplasia is excluded.[3] Cases of oral lichen planus have been reported with a malignant transformation of squamous cell carcinoma.

Investigation

Clinical examination with a thorough history, followed by tissue biopsy is routinely sufficient for the diagnosis of oral lichen planus. Histopathological examination from the biopsy of the site of lesion reveals the diagnosis of lichen planus. Immunofluorescence is an adjunctive technique in the diagnosis of lichen planus. The direct immunofluorescence of lichen planus shows “Linear pattern” in the basement zone and exhibit positive fluorescence with antifibrinogen.[33] IgA, IgG, complement C3 were seen on colloid bodies. Indirect immunofluorescence aids in the detection of antibodies in the circulating blood of the lichen planus patient. The circulating antibodies that react and bind to the basal cells of the epithelium gives rise to the “annular fluorescence” or the “string of pearls” appearance.[34]

Treatment

Even though there is no specific treatment for oral lichen planus, symptomatic treatment is indicated. Corticosteroids provide relief and first choice of drug,[35] but have other complications associated. Reticular form has best prognosis, and erosive form has a poor prognosis.

Spontaneous remission occurs in 40% of oral lichen planus. Topical corticosteroids such as flucinonide and flucicolone are used. In cases of severe erosive form, corticosteroids are injected under occlusion. Systemic corticosteroid therapy are effective against erosive and vulvovaginal lichen planus. Retinoids, cyclosporine are administered in a topical gel form. Oral photochemotherapy and extracorporeal photochemotherapy are indicated in low doses in the treatment of oral lichen planus.

Oral Lichenoid Reaction

The term lichenoid reaction was coined in 1986 by Lind. Lesions similar to lichen planus can be seen in the oral mucosa and skin. They present slight degree of alterations in the clinical and microscopic features of oral lichen planus. Termed as lichenoid reactions, which are triggered by various topical and systemic etiological factors. Oral lichenoid reactions are also considered as variants that can be regarded as a disease by itself or as an exacerbation of oral lichen planus already existing.

They are also called lichenoid drug reactions when the etiology is various oral and systemic medications and contact hypersensitivity in case of dental materials. Other predisposing factors are also put forward as the stress, genetic basis.

It clinically presents as reticular, erosive or ulcerative lesion with whitish streak. It can be seen in an atypical location such as the palate, unilateral presentation. Occur in area close to amalgam, composite resin, denture component. They share a lot of clinical features of lichen planus. Present sensitivity of the oral mucosa to spicy food. Pain may be present occurs as patches or ulcerations in most cases.

Pathogenesis

Contact allergy to dental materials involves type IV delayed hypersensivity reaction. Cell mediated immunity mainly T lymphocytes and macrophages play an important role.

Superficially resembles lichen planus.

Inflammatory infiltrate is diffuse, extends deeper into lamina propria unlike sharp band of infiltrate seen lichen planus.

Inflammatory cells such as plasma cells, eosinophils, lymphocytes are seen. Increased colloid, civette bodies are seen.

Infiltration of inflammatory cells predominantly chronic in nature surrounding the blood vessels is the striking feature seen in drug related lichenoid reaction.

Diagnosis

Allergic patch test

Immunofluorescence.

Management

Removal of the causative agent

Medication modification in respect to dosages.

Conclusion

Oral lichen planus and oral lichenoid reaction even though may portray a similar clinical picture, the site of occurrence, detailed history and investigation can draw a clear line of demarcation hence establishing variable treatment protocol. Knowledge of the condition is essential to distinguish. Regular follow-up is very important as this lesion poses a chance of malignant transformation.