Risk Factors
The root cause of psoriasis is poorly understood, but the disease is likely mediated by the pathogenic activities of keratinocytes and components of both innate and acquired immune systems.1,2 Various cell types (eg, activated T cells, dendritic cells and natural killer cells) and cytokines have been implicated in the pathogenesis of psoriasis.1-4
It is also clear that psoriasis has a strong and complex genetic component that involves multiple genes.5,6 The Psoriasis Susceptibility 1 gene (PSORS1) may be responsible for up to 50% of the genetic etiology of psoriasis; thus, genetics is a significant risk factor for psoriasis.7 Multiple genome-wide linkage studies of the development of psoriasis have confirmed the involvement of PSORS1, which resides in the major histocompatibility complex region of the genome.7 The human leukocyte antigens (HLA) are also located in this region, and HLA-Cw6 is likely the major PSORS1 disease allele conferring susceptibility to early-onset psoriasis.7,8 Recent evidence from genome-wide association scans suggests that there are at least nine loci associated with psoriasis.7
Studies of monozygotic twins demonstrate a variable concordance of psoriasis incidence ranging from 35% to 66%.9-11 In addition, although 10% of the general population inherits psoriatic alleles, the disease manifests in only 2%–3% of the population.12 Taken together, these findings suggest that there are likely environmental factors that interact with an individual's genetic background to exacerbate or initiate psoriatic manifestations. Major external or environmental factors that have been found to trigger psoriatic lesions include stress, infections such as Streptococcus pyogenes, trauma or injury to skin (Koebner or isomorphic phenomenon), medications (systemic glucocorticoids, oral lithium, anti-malarial agents, interferon and beta-adrenergic blockers) and exposure to UV light.12-15
- Tanghetti EA. The role of topical vitamin D modulators in psoriasis therapy. J Drugs Dermatol. 2009;8(8 Suppl):s4-s8.
- Schön MP, Boehncke WH. Psoriasis. N Engl J Med. 2005;352(18):1899-1912.
- Bos JD, de Rie MA, Teunissen MB, et al. Psoriasis: dysregulation of innate immunity. Br J Dermatol. 2005;152(6):1098-1107.
- Nickoloff BJ, Nestle FO. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest. 2004;113(12):1664-1675.
- Gudjonsson JE, Ding J, Johnston A, et al. Assessment of the psoriatic transcriptome in a large sample: additional regulated genes and comparisons with in vitro models. J Invest Dermatol. 2010(7);130:1829-1840.
- Suarez-Farinas M, Fuentes-Duculan J, Lowes M, et al. Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol. 2011;131(2):391-400.
- Nestle F, Kaplan D, Barker J. Psoriasis. N Engl J Med. 2009;361:496-509.
- Henseler T, Christophers E. Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. J Am Acad Dermatol. 1985;13(3):450-456.
- Brandrup F, Holm N, Grunnet N, et al. Psoriasis in monozygotic twins: variations in expression in individuals with identical genetic constitution. Acta Derm Venereol. 1982;62(3):229-236.
- Duffy DL, Spelman LS, Martin NG. Psoriasis in Australian twins. J Am Acad Dermatol. 1993;29(3):428-434.
- Farber EM, Nall ML, Watson W. Natural history of psoriasis in 61 twin pairs. Arch Dermatol. 1974;109(2):207-211.
- National Psoriasis Foundation website. About Psoriasis: Causes of Psoriasis. psoriasis.org/netcommunity/ sublearn01_pscauses. Accessed March 14, 2011.
- Elder JT, Bruce AT, Gudjonsson JE, et al. Molecular dissection of psoriasis: integrating genetics and biology. J Invest Dermatol. 2010;130(5):1213-1226.
- Weiss G, Shemer A, Trau H. The Koebner phenomenon: review of the literature. J Eur Acad Dermatol Venereol. 2002;16(3):241-248.
- Gudjonsson J, Elder J. Psoriasis. In Wolff K, Goldsmith L, Katz S, et al., eds. Fitzpatrick's Dermatology in General Medicine. 7th ed., vol. 1. New York, NY: McGraw Hill; 2008.
