Psoriasis Pathogenesis and Risk Factors

Genetic Factors

The American Academy of Dermatology suggests that the strongest genetic determinant of psoriasis is the HLA-Cw6 allele, which represents the major susceptibility gene for the disease, with at least 8 chromosomal loci identified with statistically significant evidence for linkage to psoriasis 1, 2
The low penetrance of these genetic factors indicates that additional genetic risk factors and environmental triggers are required for disease expression, according to the American Academy of Dermatology 1, 2

Psoriasis is an immune-mediated organ-specific inflammatory disease, characterized by dysregulated T-cell activation, particularly TH1 and TH17 subsets, which play central roles in disease pathogenesis, as stated by the American Academy of Dermatology 1, 2, 3
The disease involves altered levels of chemokines and integrins, affecting migration of T cells, dermal dendritic cells, macrophages, and neutrophils into plaques, and increased expression of TNF-α, interferon-γ, and IL-12/23-dependent genes in lesional skin, according to the American Academy of Dermatology 1, 2

The American Academy of Dermatology notes that multiple environmental factors, including medications such as lithium, antimalarials, beta-blockers, and NSAIDs, can trigger or exacerbate psoriasis 1, 2, 4, 5
Other environmental factors, such as skin trauma, infections, stress, and alcohol consumption, can also precipitate or worsen the disease, as stated by the American Academy of Dermatology 1, 2, 4, 6

The American Academy of Dermatology suggests that obesity and weight gain are strong risk factors for developing psoriasis, with a severity-dependent relationship, and that multiple measures of obesity are substantial risk factors, with the highest relative risk in those with highest BMIs 2, 5
The pooled odds ratio for obesity in psoriatic patients is 1.66, increasing to 2.23 in moderate-to-severe disease, according to the American Academy of Dermatology 5