What is the pathogenesis of lichen planus?

Pathogenesis of Lichen Planus

Lichen planus is a T-cell mediated autoimmune disease characterized by cytotoxic lymphocyte-driven destruction of basal keratinocytes, triggered by altered self-antigens in genetically susceptible individuals. 1, 2

Core Immunopathogenic Mechanisms

Primary Cellular Response

• Cytotoxic T lymphocytes are the principal effector cells, directly attacking basal keratinocytes through cell-mediated cytotoxicity 3, 2
• The immunologic process results in vacuolar degeneration, lysis of basal cells, and ultimately liquefaction of the basal cell layer 3
• T-cell autoimmunity targets keratinocytes as the primary target cell, with altered self-antigens on basal keratinocyte surfaces serving as the antigenic trigger 4, 2

Supporting Inflammatory Pathways

• Th1 and IL-23/Th-17 axis cytokines amplify the cytotoxic T cell response, though cytotoxic T lymphocytes remain the dominant mechanism 2
• Mast cells, intercellular adhesion molecule-1 (ICAM-1), and major histocompatibility complex class II antigens participate in the inflammatory cascade 3
• Other immunocytes and inflammatory pathways complement these primary mechanisms 2

Triggering Factors in Susceptible Individuals

Environmental and External Triggers

• Hepatitis C virus infection can trigger lichen planus through HCV-induced autoimmune reactions, with the association being a T-cell mediated autoimmune response 1, 4
• Mechanical trauma and physical stress can precipitate disease through Koebnerization 4, 2
• Psychological stress serves as a recognized trigger in genetically predisposed individuals 4, 2
• Microbiome changes may initiate disease in susceptible hosts 2

Drug and Contact-Induced Mechanisms

• Various drugs can cause lichenoid reactions by modifying self-antigens on basal keratinocytes, making them targets for T-cell response 4
• Contact allergens like dental amalgam may trigger lichenoid reactions that are clinically and histologically indistinguishable from idiopathic lichen planus 4
• Altered self-antigens modified by viruses or drugs are believed to be the targets of the T-cell response 4

Genetic Susceptibility

• Human leucocyte antigen (HLA) class II antigen associations indicate genetic predisposition to the disease 3
• Genetically susceptible individuals require environmental triggers to develop clinical disease 2

Clinical Implications of Pathogenesis

Disease Characteristics

• The chronic inflammatory nature results from persistent T-cell mediated immune activation 3, 2
• Severe pain and burning sensation in oral lichen planus reflect the intensity of basal cell destruction and inflammatory mediator release 3
• The disease affects skin, scalp, mucous membranes, and nails due to the ubiquitous distribution of target keratinocytes 4

Differential Pathogenesis from Related Conditions

• Lichen planus is characterized by cellular autoimmune response (lymphocytic-mediated), distinguishing it from mucous membrane pemphigoid which involves immunoglobulin-mediated humoral autoimmunity 5
• Epitope spreading phenomenon may explain rare cases where lichen planus evolves into other autoimmune disorders over years 5
• Cellular immunity plays a central role, which may explain associations with other immune-mediated conditions like retinal vasculitis 6

Common Pitfalls in Understanding Pathogenesis

• Do not confuse lichenoid drug reactions with idiopathic lichen planus—while clinically and histologically similar, drug-induced cases have identifiable external triggers modifying keratinocyte antigens 4
• The etiology remains incompletely understood despite clear immune-mediated mechanisms, so avoid attributing the disease to a single cause 4, 2
• Autoimmune mechanisms are established, but specific autoantigens remain poorly characterized 2