Oral lichen planus - Review on etiopathogenesis

Abstract

Oral lichen planus (OLP) is a chronic mucocutaneous disease of uncertain etiopathogenesis. Several factors including stress, genetics, systemic diseases, viruses, dental restorative materials and drugs have been implicated as causative agents. The disease seems to be mediated by an antigen specific mechanism, activating cytotoxic T cells, and non specific mechanisms like mast cell degranulation and matrix metalloproteinase activation. Further clarity on the pathogenesis will aid in modifying therapeutic interventions, thus significantly reducing the morbidity of OLP patients.

INTRODUCTION

Oral lichen planus (OLP) is a chronic, autoimmune mucocutaneous disease, occurring most commonly in the middle aged women. Lichen planus may also occur concurrently or independently in the skin and the genital, anal, esophageal, nasal and laryngeal mucosae. The prevalence of oral lichen planus in general population varies from 1-2%.[1] There is no racial predilection, and the disease appears to be pan racial.[1,2] Andreasen reported that the average age of occurrence in males and females is 40-49 years and 50-59 years, respectively.[3] However, few cases have been reported in children as young as 6 months.[4]

Clinically the oral lesions have been grouped into reticular, papular, plaque like, atrophic, erosive and bullous forms.[3] OLP usually occurs in a bilaterally symmetrical pattern, commonly involving buccal mucosa, gingivae and dorsum of the tongue.[5] The lesions are usually painless, though pain and burning sensation are associated with erosive and atrophic lesions.[6]

ETIOLOGY

The etiology of OLP appears to be multifactorial and complicated. Earlier studies have implicated stress, anxiety, depression as the causes for OLP.[3,5,7,8] However, whether stress is the cause or the consequence, was left undetermined. Familial cases of OLP have been reported and role of genetic predisposition was considered. Watanabe T et al. concluded that human leukocyte antigen (HLA) associated genetic factors play a certain role in the pathogenesis of OLP.[9] Hedberg and associates reported that epithelium involved by OLP was consistently positive for HLA-DR.[10]

Lodi G et al. reported that lichen planus is sometimes associated with infections or auto immune diseases and / or neoplasia, but the association had not been established.[11] Certain systemic diseases like diabetes mellitus, hypertension, ulcerative colitis, myasthenia gravis, lupus erythematosus, etc were considered to be associated with OLP.[12,13] A more consistent association was found between chronic liver disease and erosive form of OLP.[14] Recent studies indicate an association between Hepatitis C Virus (HCV) and OLP.[15–21] HCV is a hepatotrophic Ribonucleic acid (RNA) virus, which possibly alters the antigenecity of the epidermis, causing an interaction with activated T- cells, or acts through a modulation of the quality of host immune response.[18]

Oral lichenoid reactions caused by drugs and dental restorative materials have been considered as variants of OLP. Drugs implicated are non – steroidal anti inflammatory agents, sulfonyl ureas, beta blockers, oral hypoglycemic agents, dapsone, pencillamine. Dental restorative materials like amalgam, composite, acrylic, gold have been reported to cause lichenoid reactions. Lichenoid lesions have also been reported in tobacco chewers; however, the causative role of tobacco in the pathogenesis of OLP has not been identified.[22]

PATHOGENESIS

Current literature suggests that OLP is caused by cluster of differentiation 8 (CD-8) cell mediated damage to the basal keratinocytes leading to apoptosis. The antigen inciting the cytotoxic T cells could be any of the above mentioned factors including stress, chronic liver disease, HCV virus, dental restorative materials and/or drugs.[22] The main event in the pathogenesis appears to be increased production of cytokines leading to the recruitment of Langerhans cells and clonal expansion of cytotoxic cells. Langerhans cells produce increased amounts of interferon -alpha (IFN - α), which further activates cytotoxic cell mediated apoptosis, via the keratinocyte caspase cascade.[1,23] Intercellular adhesion molecules enhance the attraction of cytotoxic T cells. Interferon -γ production increases the apoptosis through the up regulation of p53 and matrix metallo proteinase -1 (MMP-1).[1] Non specific mechanisms like mast cell degranulation and MMP -1 activation further aggravate the T cell accumulation, basement membrane disruption by mast cell proteases and keratinocyte apoptosis (triggered by basement membrane disruption). The chronicity of the OLP lesions might be partly explained by the fact that the basement membrane disruption triggers keratinocyte apoptosis and apoptotic keratinocytes are unable to repair the breach in basement membrane.[23]

CONCLUSION

Therefore, interaction of various factors is probably responsible for the initiation, aggravation and persistence of OLP. The current treatment modalities are not only inadequate in treating all patients and preventing recurrences, but also have significant side effects. Further clarity on the pathogenesis will aid in modifying therapeutic interventions, thus significantly reducing the morbidity of OLP patients.