Lichen planus (LP) is a skin condition which shows exacerbations and remissions over time. Its etiology has not yet been established. However, lichenoid reactions are seen following contact with many substances. Some of the predisposing and triggering factors are as follows:
Gene polymorphisms of various HLA markers, as well as the presence of inflammatory cytokines and chemokines have been linked to LP development. Some HLA antigens have been observed to be of higher frequency in patients with LP, such as HLA-A3, A11, A26, B3, B5 and DR1.
Contact with dental materials
Many dental restorative materials may trigger LP in the oral cavity, such as silver, gold, palladium, cobalt, and epoxy resins (commonly called composite). Many researchers think that these are due to delayed (Type IV) hypersensitivity reactions caused by allergy to the materials used, with patch tests being positive in over 90% of these patients, as compared to less than 4% in subjects with oral lichen planus (OLP). These are therefore classified as oral lichenoid reactions rather than OLP.
Medications associated with oral LP include:
- non-steroidal anti-inflammatory drugs (NSAIDs)
- some antihypertensives such as beta-blockers
- some hypoglycemic drugs
- some oral anti-retrovirals
- anti-arthritic drugs
Chronic hepatitis C infection has been implicated in the pathogenesis of OLP. This association is stronger in Mediterranean countries and in Japan. The interferons and ribavirin that are used to treat this condition are also postulated to be the reason for the increased incidence of LP in this patient group.
Other infectious agents associated with this condition include:
- human papillomavirus (HPV)
- Epstein-Barr virus
- human immunodeficiency virus.
Some diseases caused by autoimmune reactions are associated with OLP. These include:
- primary biliary cirrhosis
- chronic active hepatitis
- myasthenia gravis
- irritable bowel disease
- ulcerative colitis
Other precipitating factors
Some food additives such as cinnamon aldehyde may be involved in the pathogenesis of OLP. Furthermore, LP is found to be exacerbated in conditions which involve anxiety or stress.
Both chewing and smoking of tobacco and betel nut have been suggested to be etiologically linked to LP. There is no greater prevalence of cigarette smoking in OLP patients, however. The lesion that occurs at the site where the betel wad is tucked into the cheek has been termed the “betel quid lichenoid lesion”.
LP has been associated with a higher risk of diabetes mellitus and hypertension, as well as hypertriglyceridemia. The triad of diabetes, hypertension, and oral LP is called Greenspan syndrome.
Breast carcinomas and metastatic adenocarcinoma have also been found to be associated with LP. The skin at graft sites is seen to be infiltrated with lymphocytes leading to typical basal cell vacuolar degeneration and disruption of the basement membrane underlying the epithelium.
Pathogenesis of the disease
Lichen planus is an autoimmune disease supposed to be mediated by cytotoxic CD8+ T lymphocytes directed against the basal cells of the oral mucosal epithelium.
The sequence of events in LP includes:
- Expression of a non-self antigen by keratinocytes
- Detection of the antigen during immune surveillance or response to chemokines produces T-cell migration, mostly CD8+ cells, into the epithelium
- T-cells are activated either directly through antigen binding to MHC-1 on keratinocyte, or via activated CD4+ cells
- Further antigen presentation activates CD4+ helper T cells leading to further activation of CD8+ T cells
- Auto-cytotoxic CD8+ T cells target basal keratinocytes and produce apoptosis via various pathways such as tumor necrosis factor α (TNF-α).