Psoriasis risk factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Common risk factors in the development of psoriasis are genes which increase the susceptibility of developing psoriasis and environmental triggers. The presence of these risk factors may lead to auto-immunity and development of psoriasis.

• The human genome has at least nine different loci implicated in the development of psoriasis (PSORS1-9).^[1]
• PSORS-1, a part of the major histocompatibility complex (MHC) on chromosome 6p2, is the major genetic determinant of psoriasis, and is responsible for up to 50% of genetic susceptibility to the disease.^[2]
• The second most well-characterized disease-susceptibility locus (PSORS2) is found within 17q24–q25.
• Missense mutations in CARD14 gene lead to activation of the NF-κB pathway.
• Another major gene involved in the development of psoriasis is a HLA class I allele, specifically HLA-Cw6.^[3]
• Psoriatic arthritis (PsA) has been shown to be associated with human leukocyte antigen (HLA) class 1.^[4]

• Both innate and adaptive immunity are involved in the development of psoriasis.
• The key cytokines of immune system involved in the development of psoriasis are tumor necrosis factor-alpha and interferon alpha.
• The LFA-1 integrin is also important in the immune pathogenesis of psoriasis and has been known to be a target for medications used for the management of psoriasis.
• Within the immune system, the development of psoriasis is based upon four key pathways/interactions:
  • Antigen presentation
  • NF-κB signaling
  • IL-23/IL-17 axis
  • Type I interferon (IFN) pathway

The environmental factors implicated in the development or aggravation of psoriasis are:^{[5][6][7][8][9][10][11]}

• Stress (physical and mental)
• Smoking
• Excessive alcohol consumption
• Infection (Streptococcal, HIV)
• Seasonal variation
• Medications (lithium, beta blockers, pegylated interferon alpha-2b, siltuximab)
• Obesity
• Skin injury
• Skin dryness

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