Psoriasis: Core Concepts

Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal hyperproliferation and abnormal keratinocyte differentiation. The normal epidermal transit time (from basal layer to surface shedding) is approximately 28 days; in psoriatic skin, this is accelerated to 3-5 days. This hyperproliferation is driven by the IL-23/Th17 immune axis: activated dendritic cells produce IL-23, which stimulates Th17 lymphocytes to secrete IL-17A, IL-17F, and IL-22. IL-17 recruits neutrophils (forming Munro microabscesses in the stratum corneum) and stimulates keratinocyte proliferation and production of antimicrobial peptides (defensins, cathelicidin/LL-37) and chemokines that perpetuate the inflammatory cycle. IL-22 promotes epidermal thickening (acanthosis). The dermal papillary vessels become dilated and tortuous (Auspitz sign = pinpoint bleeding when scale is removed), and there is a dense perivascular lymphocytic infiltrate. The disease follows a relapsing-remitting course with genetic susceptibility (HLA-Cw6 strongest association) and environmental triggers (Koebner phenomenon, infections, medications, stress). Psoriasis is now recognized as a systemic inflammatory disease with associated comorbidities including psoriatic arthritis (30%), cardiovascular disease, metabolic syndrome, and depression.