Psoriasis Etiopathogenesis: Causes and Mechanisms

Etiopathogenesis of Psoriasis

The etiopathogenesis of psoriasis involves a complex interaction between genetic, immunologic, and environmental factors that lead to chronic skin inflammation and hyperproliferation of keratinocytes.

1. Genetic Predisposition

• Psoriasis is a polygenic disease involving multiple genes.
• HLA-Cw6 is the most strongly associated gene, particularly in early-onset cases.
• Other susceptibility loci include:
  • PSORS1–9 regions.
  • Genes regulating immune pathways, such as IL-23, IL-12, and TNF-α.

2. Environmental Triggers

Specific external and internal factors can trigger or exacerbate psoriatic symptoms:

• Infections: Notably streptococcal throat infections, which are linked to guttate psoriasis.
• Trauma: The Koebner phenomenon, where lesions develop at sites of skin injury.
• Drugs: Medications such as lithium, β-blockers, antimalarials, and NSAIDs.
• Stress: Psychological stress is a known factor in disease flare-ups.
• Climate: Cold and dry weather conditions often worsen symptoms.

3. Immune System Dysregulation

Psoriasis is primarily a T-cell mediated autoimmune disease:

• The process is initiated by the activation of dendritic cells in the skin.
• Dendritic cells release IL-23, IL-12, and TNF-α, which subsequently activate:
  • Th17 cells (the primary drivers).
  • Th1 cells.

Key Cytokines

• IL-23, IL-17A, TNF-α, IFN-γ, and IL-22.
• These cytokines promote sustained inflammation and keratinocyte proliferation.

4. Keratinocyte Hyperproliferation

Inflammatory cytokines stimulate keratinocytes to:

• Proliferate rapidly, resulting in thickened plaques.
• Produce additional cytokines and antimicrobial peptides.

This leads to characteristic histological changes:

• Parakeratosis: Retention of nuclei in the stratum corneum.
• Acanthosis: Epidermal hyperplasia.
• Dilated blood vessels: Dermal vascular changes leading to erythema.
• Munro microabscesses: Neutrophil accumulation in the stratum corneum.

Summary of Pathogenesis

Trigger → Dendritic cell activation → Th17/Th1 differentiation → Cytokine release → Keratinocyte proliferation and inflammation → Psoriatic plaque formation.