What is the pathophysiology of lichen planus?

Pathophysiology of Lichen Planus

Lichen planus is fundamentally a T-cell mediated autoimmune inflammatory disorder characterized by a lymphocytic response targeting the basal layer of the epidermis, resulting in vacuolar degeneration and tissue damage.

Immunopathogenesis

The pathophysiology of lichen planus involves several key immunological mechanisms:

Cellular Immune Response

• T-cell mediated autoimmunity: The primary driver is an abnormal cell-mediated immune response where CD8+ cytotoxic T lymphocytes attack basal keratinocytes 1
• Basal cell damage: T cells recognize and target self-antigens in the basal epithelial layer, causing vacuolar degeneration and apoptosis of keratinocytes 2
• Inflammatory infiltrate: Characteristic dense band-like lymphocytic infiltrate occurs at the dermal-epidermal junction 3

Molecular Mechanisms

• Cytokine involvement: Increased production of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) 1
• Adhesion molecules: Upregulation of intercellular adhesion molecule-1 (ICAM-1) facilitates T-cell migration and adhesion 3
• MHC class II expression: Abnormal expression of major histocompatibility complex class II antigens on keratinocytes enhances antigen presentation 3

Potential Triggers and Risk Factors

Several factors have been implicated in triggering or exacerbating lichen planus:

Genetic Factors

• Genetic predisposition: Family history is reported in approximately 12% of patients 4
• HLA associations: Specific human leukocyte antigen (HLA) class II antigens have been associated with lichen planus susceptibility 4

Environmental Triggers

• Cross-reactive T cells: Memory T cells specific for previously encountered viruses may cross-react with other antigens in the absence of cognate antigen 2
• Viral associations: Hepatitis C virus (HCV) has been epidemiologically linked to lichen planus in some geographical regions 4
• Medications: Certain drugs can trigger lichenoid reactions that mimic true lichen planus 5
• Contact allergens: Dental materials and other allergens may induce lichenoid reactions through contact hypersensitivity 5

Disease Variants and Clinical Correlation

The pathophysiological mechanisms manifest differently across various forms of lichen planus:

• Cutaneous LP: Primarily affects skin with characteristic Wickham's striae
• Mucosal LP: Most commonly affects oral mucosa but can involve genital mucosa
• Overlap syndromes: Some cases show features of both lichen planus and lichen sclerosus, particularly in genital regions 4

Pathophysiological Progression

The disease process follows a characteristic sequence:

1. Initiation: Antigen recognition by T cells (either self-antigens or cross-reactive epitopes)
2. Amplification: Recruitment of additional inflammatory cells and cytokine release
3. Tissue damage: Vacuolar degeneration of basal cells and liquefaction of the basement membrane
4. Chronicity: Persistent inflammation leads to tissue remodeling and potential scarring

Clinical Implications

Understanding the pathophysiology has important clinical implications:

• Therapeutic targets: Treatments primarily aim to suppress the T-cell mediated immune response, with corticosteroids being first-line therapy 3
• Malignant transformation: The chronic inflammatory state may contribute to the small but significant risk of malignant transformation, particularly in oral lichen planus 6
• Comorbidities: Association with other autoimmune conditions suggests shared pathophysiological mechanisms 4

Key Distinctions

It's important to differentiate true lichen planus from lichenoid reactions:

• Lichen planus: Primary autoimmune disorder with characteristic histopathology
• Lichenoid drug reactions: Medication-induced with similar but distinguishable histopathological features
• Contact lichenoid reactions: Triggered by specific allergens, often dental materials 5

The pathophysiological understanding of lichen planus continues to evolve, with emerging research focusing on novel immune pathways that may lead to targeted therapies such as JAK inhibitors and biologics targeting IL-12/23 and IL-17 pathways 1.