Editing Psoriasis (section)

==Causes==
The cause of psoriasis is not fully understood. Genetics, seasonal changes, skin damage, climate, [[Immunodeficiency|immunocompromised]] state, specific infections, and the use of some medications have been connected with different types of psoriasis.<ref name="Prieto2013" /><ref name=":0" />

===Genetics===
{{See also|List of human leukocyte antigen alleles associated with cutaneous conditions}}
Around one-third of people with psoriasis report a [[family history (medicine)|family history]] of the disease, and researchers have identified genetic [[locus (genetics)|loci]] associated with the condition. [[twin|Identical twin]] studies suggest a 70% chance of a twin developing psoriasis if the other twin has the disorder. The risk is around 20% for fraternal twins. These findings suggest both a genetic susceptibility and an environmental response in developing psoriasis.<ref name=Krueger>{{cite journal | vauthors = Krueger G, Ellis CN | title = Psoriasis--recent advances in understanding its pathogenesis and treatment | journal = Journal of the American Academy of Dermatology | volume = 53 | issue = 1 Suppl 1 | pages = S94–100 | date = July 2005 | pmid = 15968269 | doi = 10.1016/j.jaad.2005.04.035 }}</ref>

Psoriasis has a strong hereditary component, and many genes are associated with it, but how those genes work together is unclear. Most of the identified genes relate to the [[immune system]], particularly the [[major histocompatibility complex]] (MHC) and [[T cells]]. Genetic studies are valuable due to their ability to identify molecular mechanisms and pathways for further study and potential medication targets.<ref name=Nestle>{{cite journal | vauthors = Nestle FO, Kaplan DH, Barker J | title = Psoriasis | journal = The New England Journal of Medicine | volume = 361 | issue = 5 | pages = 496–509 | date = July 2009 | pmid = 19641206 | doi = 10.1056/NEJMra0804595 | s2cid = 203791161 | doi-access = free }}</ref>

Classic genome-wide [[linkage analysis]] has identified nine loci on different [[chromosome]]s associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (''[[PSORS1]]'' through ''PSORS9''). Within those loci are genes on pathways that lead to inflammation. Certain variations ([[mutation]]s) of those genes are commonly found in psoriasis.<ref name=Nestle/> [[Genome-wide association study|Genome-wide association scans]] have identified other genes that are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signal [[proteins]], which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.<ref name=Nestle/>

The major determinant is ''PSORS1'', which probably accounts for 35–50% of psoriasis heritability.<ref>{{cite journal | vauthors = Smith CH, Barker JN | title = Psoriasis and its management | journal = BMJ | volume = 333 | issue = 7564 | pages = 380–4 | date = August 2006 | pmid = 16916825 | pmc = 1550454 | doi = 10.1136/bmj.333.7564.380 }}</ref> It controls genes that affect the immune system or encode skin proteins that are overabundant with psoriasis. ''PSORS1'' is located on [[chromosome 6]] in the MHC, which controls important immune functions. Three genes in the ''PSORS1'' locus have a strong association with psoriasis vulgaris: ''HLA-C'' variant ''HLA-Cw6'',<ref name="Prieto2013"/> which encodes an MHC class I protein; ''[[CCHCR1]]'', variant WWC, which encodes a [[coiled coil]] protein overexpressed in psoriatic [[epidermis]]; and ''[[CDSN]]'', variant allele 5, which encodes [[corneodesmosin]], a protein expressed in the granular and [[cornified layer]]s of the epidermis and upregulated in psoriasis.<ref name=Nestle/>

Two major immune system genes under investigation are interleukin-12 subunit beta (''IL12B'') on [[Chromosome 5 (human)|chromosome 5q]], which expresses interleukin-12B; and ''[[IL23R]]'' on chromosome 1p, which expresses the interleukin-23 receptor and is involved in T cell differentiation. Interleukin-23 receptor and ''IL12B'' have both been strongly linked with psoriasis.<ref name="Prieto2013"/> T cells are involved in the inflammatory process that leads to psoriasis.<ref name=Nestle/> These genes are on the pathway that upregulates tumor necrosis factor-α and [[NF-κB|nuclear factor κB]], two genes involved in inflammation.<ref name=Nestle/> The first gene directly linked to psoriasis was identified as the ''[[CARD14]] ''gene located in the ''PSORS2'' locus. A rare mutation in the gene encoding for the ''[[CARD14]]''-regulated protein plus an environmental trigger was enough to cause plaque psoriasis (the most common form of psoriasis).<ref name = Jordan1>{{cite journal | vauthors = Jordan CT, Cao L, Roberson ED, Duan S, Helms CA, Nair RP, Duffin KC, Stuart PE, Goldgar D, Hayashi G, Olfson EH, Feng BJ, Pullinger CR, Kane JP, Wise CA, Goldbach-Mansky R, Lowes MA, Peddle L, Chandran V, Liao W, Rahman P, Krueger GG, Gladman D, Elder JT, Menter A, Bowcock AM | title = Rare and common variants in CARD14, encoding an epidermal regulator of NF-kappaB, in psoriasis | journal = American Journal of Human Genetics | volume = 90 | issue = 5 | pages = 796–808 | date = May 2012 | pmid = 22521419 | pmc = 3376540 | doi = 10.1016/j.ajhg.2012.03.013 }}</ref><ref name = Jordan2>{{cite journal | vauthors = Jordan CT, Cao L, Roberson ED, Pierson KC, Yang CF, Joyce CE, Ryan C, Duan S, Helms CA, Liu Y, Chen Y, McBride AA, Hwu WL, Wu JY, Chen YT, Menter A, Goldbach-Mansky R, Lowes MA, Bowcock AM | title = PSORS2 is due to mutations in CARD14 | journal = American Journal of Human Genetics | volume = 90 | issue = 5 | pages = 784–95 | date = May 2012 | pmid = 22521418 | pmc = 3376640 | doi = 10.1016/j.ajhg.2012.03.012 }}</ref>

===Lifestyle===
Conditions reported as worsening the disease include chronic infections, stress, and changes in season and [[climate]].<ref name="Prieto2013"/> Other factors that might worsen the condition include hot water, scratching psoriasis skin lesions, [[Xeroderma|skin dryness]], [[Alcoholism|excessive alcohol consumption]], [[cigarette smoking]], and [[obesity]].<ref name=Prieto2013/><ref name=Clarke2011>{{cite journal | vauthors = Clarke P | title = Psoriasis | journal = Australian Family Physician | volume = 40 | issue = 7 | pages = 468–73 | date = July 2011 | pmid = 21743850 | url = http://www.racgp.org.au/download/documents/AFP/2011/July/201107clark.pdf | access-date = 4 March 2014 | archive-date = 27 June 2019 | archive-url = https://web.archive.org/web/20190627155636/https://www.racgp.org.au/download/documents/AFP/2011/July/201107clark.pdf | url-status = live }}</ref><ref name=Richard2013/><ref name=Shu2019>{{cite journal | vauthors = Ko SH, Chi CC, Yeh ML, Wang SH, Tsai YS, Hsu MY | title = Lifestyle changes for treating psoriasis | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD011972 | date = July 2019 | issue = 7 | pmid = 31309536 | pmc = 6629583 | doi = 10.1002/14651858.CD011972.pub2 | id = CD011972 }}</ref> The effects of stopping cigarette smoking or alcohol misuse have yet to be studied as of 2019.<ref name=Shu2019 />

===HIV===
The rate of psoriasis in [[human immunodeficiency virus]]-positive (HIV) individuals is comparable to that of HIV-negative individuals, but psoriasis tends to be more severe in people infected with HIV.<ref name="Cedeno2011"/> A much higher rate of psoriatic arthritis occurs in HIV-positive individuals with psoriasis than in those without the infection.<ref name="Cedeno2011"/> The immune response in those infected with HIV is typically characterized by [[cytokine|cellular signals]] from [[T helper cell|T<sub>h</sub>2 subset of CD4+ helper T cells]],<ref name="Fife2007">{{cite journal | vauthors = Fife DJ, Waller JM, Jeffes EW, Koo JY | title = Unraveling the paradoxes of HIV-associated psoriasis: a review of T-cell subsets and cytokine profiles | journal = Dermatology Online Journal | volume = 13 | issue = 2 | pages = 4 | date = May 2007 | doi = 10.5070/D34SF63339 | pmid = 17498423 | url = http://dermatology.cdlib.org/132/reviews/HIV/fife.html | url-status = live | archive-url = https://web.archive.org/web/20080421173119/http://dermatology.cdlib.org/132/reviews/HIV/fife.html | archive-date = 21 April 2008 }}</ref> whereas the immune response in psoriasis vulgaris is characterized by a pattern of cellular signals typical of [[Th1 cell|T<sub>h</sub>1 subset of CD4+ helper T cells]] and [[T helper 17 cell|T<sub>h</sub>17 helper T cells]].<ref name="Wong2013">{{cite journal | vauthors = Wong T, Hsu L, Liao W | title = Phototherapy in psoriasis: a review of mechanisms of action | journal = [[Journal of Cutaneous Medicine and Surgery]] | volume = 17 | issue = 1 | pages = 6–12 | date = January–February 2013 | pmid = 23364144 | pmc = 3736829 | doi = 10.2310/7750.2012.11124 }}</ref><ref name="Martin2013">{{cite journal | vauthors = Martin DA, Towne JE, Kricorian G, Klekotka P, Gudjonsson JE, Krueger JG, Russell CB | title = The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings | journal = The Journal of Investigative Dermatology | volume = 133 | issue = 1 | pages = 17–26 | date = January 2013 | pmid = 22673731 | pmc = 3568997 | doi = 10.1038/jid.2012.194 }}</ref> The diminished CD4+-T cell presence is thought to cause overactivation of CD8+-T cells, which are responsible for the exacerbation of psoriasis in HIV-positive people. Psoriasis in those with HIV/AIDS is often severe and may be untreatable with conventional therapy.<ref name=Rice>{{cite web |title=Images of Memorable Cases: Case 34 |quote=This AIDS patient presented with a pruritic eruption over most of his body |work=Connexions |publisher=Rice University |url=http://cnx.org/content/m14956/latest/ |access-date=21 December 2009 |archive-date=10 July 2012 |archive-url=https://archive.today/20120710172141/http://cnx.org/content/m14956/latest/ |url-status=live }}</ref> In those with long-term, well-controlled psoriasis, new HIV infection can trigger a severe flare-up of psoriasis and/or psoriatic arthritis.{{Medical citation needed|date=October 2019}}

=== Microbes ===
Psoriasis has been described as occurring after [[strep throat]], and may be worsened by skin or gut colonization with ''[[Staphylococcus aureus]]'', ''[[Malassezia]]'' spp., and ''[[Candida albicans]]''.<ref name=":0">{{cite journal | vauthors = Fry L, Baker BS | title = Triggering psoriasis: the role of infections and medications | journal = Clinics in Dermatology | volume = 25 | issue = 6 | pages = 606–15 | date = 2007 | pmid = 18021899 | doi = 10.1016/j.clindermatol.2007.08.015 }}</ref> Guttate psoriasis often affects children and adolescents and can be triggered by a recent [[group A streptococcal infection]] ([[tonsillitis]] or [[pharyngitis]]).<ref name="Rendon2019" />

===Medications===
Drug-induced psoriasis may occur with [[beta blocker]]s,<ref name=Jain2012 /> [[lithium]],<ref name=Jain2012 /> [[antimalarial medication]]s,<ref name=Jain2012 /> [[nonsteroidal anti-inflammatory drug]]s,<ref name=Jain2012 /> [[terbinafine]], [[calcium channel blockers]], [[captopril]], [[glyburide]], [[granulocyte colony-stimulating factor]],<ref name=Jain2012 /> [[interleukin]]s, [[interferon]]s,<ref name=Jain2012 /> [[Hypolipidemic agent|lipid-lowering medications]],<ref name="Andrews"/>{{rp|197}} and paradoxically [[TNF inhibitor]]s such as [[infliximab]] or [[adalimumab]].<ref name="Guerra2013">{{cite journal | vauthors = Guerra I, Gisbert JP | title = Onset of psoriasis in patients with inflammatory bowel disease treated with anti-TNF agents | journal = Expert Review of Gastroenterology & Hepatology | volume = 7 | issue = 1 | pages = 41–8 | date = January 2013 | pmid = 23265148 | doi = 10.1586/egh.12.64 | s2cid = 207210831 }}</ref> Withdrawal of [[corticosteroid]]s (topical steroid cream) can aggravate psoriasis due to the [[rebound effect]].<ref name=Weller2008>{{cite book|vauthors=Weller R, Hunter JA, Savin J, Dahl M|title=Clinical dermatology|year=2008|publisher=Blackwell|location=Malden, MA|isbn=978-1-4443-0009-3|pages=54–70|url=https://books.google.com/books?id=5RHM0Nerk9gC&q=dermatology|edition=4th|access-date=19 November 2020|archive-date=24 February 2024|archive-url=https://web.archive.org/web/20240224040825/https://books.google.com/books?id=5RHM0Nerk9gC&q=dermatology|url-status=live}}</ref>