Pharmacotherapy of Psoriasis

Introduction & pathogenesis

• Psoriasis is a chronic, immune-mediated, T-lymphocyte–driven systemic inflammatory disease with well-demarcated erythematous scaling plaques; it waxes and wanes, is never cured, and is treated to control — drugs diminish lesions but do not eradicate disease. It is the most common immune-mediated inflammatory disease worldwide (US prevalence ≈3%).
• Pathogenic spine — the IL-23/T_H17 axis: dermal dendritic cells secrete TNF-α, IL-12 and IL-23; IL-23 (p19/p40) activates/maintains T_H17 cells → IL-17A binds keratinocyte IL-17RA → neutrophilic inflammation, aberrant differentiation and keratinocyte hyperproliferation. Upregulated JAK/STAT (incl. TYK2) signalling amplifies the cascade — the rationale map for every targeted drug.
• Why pharmacology matters: each drug class maps onto a defined step — keratinocyte hyperproliferation (vitamin D₃ analogues, retinoids, anthralin), the TNF-α/IL-23/IL-17 cytokine axis (biologics), T-cell/calcineurin (ciclosporin), DNA/folate & adenosine (methotrexate), and intracellular second messengers (PDE-4, JAK/TYK2 inhibitors).
• Triggers/aggravators (Koebner phenomenon = lesions at trauma sites): streptococcal infection, smoking, alcohol, obesity, stress; drug triggers — β-blockers, lithium, NSAIDs, antimalarials (chloroquine), and corticosteroid withdrawal. ~75% have ≥1 comorbidity — psoriatic arthritis (PsA, ~30%), metabolic syndrome, CV disease; PsA drives biologic choice.
• Severity & treat-to-target: assessed by BSA, PASI, sPGA and DLQI — "rule of tens" (PASI ≥10 / DLQI ≥10 / BSA ≥10% = severe). 2017 NPF target = BSA ≤1%. Stepwise ladder: topical → phototherapy → systemic (traditional then biologic); continuous therapy has largely replaced rotational therapy.