Editing Acne (section)

== Causes ==
Risk factors for the development of acne, other than genetics, have not been conclusively identified. Possible secondary contributors include hormones, infections, diet, and stress. Studies investigating the impact of smoking on the incidence and severity of acne have been inconclusive.<ref name="Bhate2013"/><ref>{{cite book | vauthors = Rigopoulos E, Korfitis C |year=2014 |title=Pathogenesis and Treatment of Acne and Rosacea|chapter=Acne and Smoking| veditors = Zouboulis C, Katsambas A, Kligman AM |location=Berlin |publisher=Springer-Verlag |pages=167–170 |isbn=978-3-540-69374-1}}</ref><ref>{{cite book |author1=InformedHealth.org |title=Acne: Overview |date=26 September 2019 |publisher=Institute for Quality and Efficiency in Health Care |url=https://www.ncbi.nlm.nih.gov/books/NBK279211/ |access-date=23 July 2021 |archive-date=4 August 2020 |archive-url=https://web.archive.org/web/20200804103000/https://www.ncbi.nlm.nih.gov/books/NBK279211/ |url-status=live }}</ref> Cleanliness ([[hygiene]]) and sunlight are not associated with acne.<ref name="Schnopp2011"/>

===Genes===
Acne appears to be highly [[Heritability|heritable]]; [[gene]]tics explain 81% of the variation in the population.<ref name="Zaenglein2018"/> Studies performed in affected [[twin studies|twins]] and [[first-degree relatives]] further demonstrate the strongly inherited nature of acne.<ref name="Bhate2013"/><ref name="Zaenglein2018"/> Acne susceptibility is likely due to the influence of multiple genes, as the disease does not follow a classic [[Mendelian inheritance|(Mendelian)]] inheritance pattern. These gene candidates include [[Polymorphism (biology)|certain variations]] in [[TNF-alpha|tumor necrosis factor-alpha (TNF-alpha)]], [[IL-1 alpha]], and [[CYP1A1]] genes, among others.<ref name="Taylor2011"/> The 308&nbsp;G/A [[single nucleotide polymorphism]] variation in the gene for [[Tumor necrosis factors|TNF]] is associated with an increased risk for acne.<ref name=Yang2014>{{cite journal | vauthors = Yang JK, Wu WJ, Qi J, He L, Zhang YP | title = TNF-308 G/A polymorphism and risk of acne vulgaris: a meta-analysis | journal = PLOS ONE | volume = 9 | issue = 2 | pages = e87806 | date = February 2014 | pmid = 24498378 | pmc = 3912133 | doi = 10.1371/journal.pone.0087806 | type = Systematic Review & Meta-Analysis | bibcode = 2014PLoSO...987806Y | doi-access = free }}</ref> Acne can be a feature of rare genetic disorders such as [[Apert's syndrome]].<ref name="Zaenglein2018">{{cite journal | vauthors = Zaenglein AL | title = Acne Vulgaris | journal = The New England Journal of Medicine | volume = 379 | issue = 14 | pages = 1343–1352 | date = October 2018 | pmid = 30281982 | doi = 10.1056/NEJMcp1702493 | s2cid = 52914179 | type = Review }}</ref> Severe acne may be associated with [[XYY syndrome]].<ref name="FitzAtlas">{{cite book| vauthors = Fitzpatrick TB |title=Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology|date=2005|publisher=McGraw-Hill Medical Pub. Division|location=New York|isbn=978-0071440196|page=2|edition=5th}}</ref>

===Hormones===
Hormonal activity, such as occurs during [[menstruation|menstrual cycles]] and [[puberty]], may contribute to the formation of acne. During puberty, an increase in sex hormones called [[androgen]]s causes the skin follicle glands to grow larger and make more oily sebum.<ref name="women"/> The androgen hormones [[testosterone]], [[dihydrotestosterone]] (DHT), and [[dehydroepiandrosterone]] (DHEA) are all linked to acne. High levels of [[growth hormone]] (GH) and [[insulin-like growth factor 1]] (IGF-1) are also associated with worsened acne.<ref name=Harper2011>{{cite book| vauthors = Hoeger PH, Irvine AD, Yan AC |chapter=Chapter 79: Acne|title=Harper's Textbook of Pediatric Dermatology|year=2011|publisher=Wiley-Blackwell|location=New Jersey|isbn=978-1-4443-4536-0|edition=3rd}}</ref> Both androgens and IGF-1 seem to be essential for acne to occur, as acne does not develop in individuals with [[complete androgen insensitivity syndrome]] (CAIS) or [[Laron syndrome]] (insensitivity to GH, resulting in very low IGF-1 levels).<ref name="ShalitaRosso2011">{{cite book |veditors=Shalita AR, Del Rosso JQ, Webster G |title=Acne Vulgaris|url=https://books.google.com/books?id=CIPOBQAAQBAJ&pg=PA33|date=March 2011|publisher=CRC Press|isbn=978-1-61631-009-7|pages=33–|url-status=live|archive-url=https://web.archive.org/web/20161209210819/https://books.google.com/books?id=CIPOBQAAQBAJ&pg=PA33|archive-date=9 December 2016}}</ref><ref name="ZouboulisKatsambas2014">{{cite book |veditors=Zouboulis CC, Katsambas AD, Kligman AM |title=Pathogenesis and Treatment of Acne and Rosacea|url=https://books.google.com/books?id=vnQqBAAAQBAJ&pg=PA121|date=July 2014|publisher=Springer|isbn=978-3-540-69375-8|pages=121–122|url-status=live|archive-url=https://web.archive.org/web/20161210040108/https://books.google.com/books?id=vnQqBAAAQBAJ&pg=PA121|archive-date=10 December 2016}}</ref>

Medical conditions that commonly cause a high-androgen state, such as [[polycystic ovary syndrome]], [[congenital adrenal hyperplasia]], and [[Adrenal tumor|androgen-secreting tumors]], can cause acne in affected individuals.<ref name=Das2014/><ref name=Housman2014>{{cite journal | vauthors = Housman E, Reynolds RV | title = Polycystic ovary syndrome: a review for dermatologists: Part I. Diagnosis and manifestations | journal = Journal of the American Academy of Dermatology | volume = 71 | issue = 5 | pages = 847.e1–847.e10; quiz 857–8 | date = November 2014 | pmid = 25437977 | doi = 10.1016/j.jaad.2014.05.007 | type = Review }}</ref> Conversely, people who [[androgen deficiency|lack androgenic hormones]] or are [[androgen insensitivity|insensitive to the effects of androgens]] rarely have acne.<ref name=Das2014/> Pregnancy can increase androgen levels, and consequently, oily sebum synthesis.<ref name=Housman2014/><ref name=Kong2013>{{cite journal | vauthors = Kong YL, Tey HL | title = Treatment of acne vulgaris during pregnancy and lactation | journal = Drugs | volume = 73 | issue = 8 | pages = 779–87 | date = June 2013 | pmid = 23657872 | doi = 10.1007/s40265-013-0060-0 | s2cid = 45531743 | type = Review }}</ref> Acne can be a side effect of [[testosterone replacement therapy]] or [[anabolic steroid]] use.<ref name="Vary2015"/><ref>{{cite journal | vauthors = Melnik B, Jansen T, Grabbe S | title = Abuse of anabolic-androgenic steroids and bodybuilding acne: an underestimated health problem | journal = Journal of the German Society of Dermatology | volume = 5 | issue = 2 | pages = 110–7 | date = February 2007 | pmid = 17274777 | doi = 10.1111/j.1610-0387.2007.06176.x | s2cid = 13382470 | type = Review }}</ref> Over-the-counter [[bodybuilding]] and [[dietary supplement]]s often contain illegally added anabolic steroids.<ref name=Vary2015/><ref name="Joseph2015">{{cite journal | vauthors = Joseph JF, Parr MK | title = Synthetic androgens as designer supplements | journal = Current Neuropharmacology | volume = 13 | issue = 1 | pages = 89–100 | date = January 2015 | pmid = 26074745 | pmc = 4462045 | doi = 10.2174/1570159X13666141210224756 | type = Review }}</ref>

=== Infections ===
The [[Anaerobic organism|anaerobic bacterial]] species ''[[Cutibacterium acnes]]'' (formerly ''Propionibacterium acnes'') contributes to the development of acne, but its exact role is not well understood.<ref name=Bhate2013/> There are specific sub-strains of ''C. acnes'' associated with normal skin and others with moderate or severe inflammatory acne.<ref name=Simonart2013/> It is unclear whether these undesirable strains evolve on-site or are acquired, or possibly both depending on the person. These strains have the capability of changing, perpetuating, or adapting to the abnormal cycle of inflammation, oil production, and inadequate sloughing of dead skin cells from acne pores. Infection with the parasitic mite ''[[Demodex]]'' is associated with the development of acne.<ref name=Zhao2012>{{cite journal | vauthors = Zhao YE, Hu L, Wu LP, Ma JX | title = A meta-analysis of association between acne vulgaris and Demodex infestation | journal = Journal of Zhejiang University Science B | volume = 13 | issue = 3 | pages = 192–202 | date = March 2012 | pmid = 22374611 | pmc = 3296070 | doi = 10.1631/jzus.B1100285 | type = Meta-analysis }}</ref><ref name=Bhate2014>{{cite journal | vauthors = Bhate K, Williams HC | title = What's new in acne? An analysis of systematic reviews published in 2011-2012 | journal = Clinical and Experimental Dermatology | volume = 39 | issue = 3 | pages = 273–7; quiz 277–8 | date = April 2014 | pmid = 24635060 | doi = 10.1111/ced.12270 | s2cid = 29010884 | type = Review | doi-access = free }}</ref> It is unclear whether eradication of the mite improves acne.<ref name=Bhate2014/>

=== Diet ===
High-[[glycemic load|glycemic-load]] diets have been found to have different degrees of effect on acne severity.<ref name="Mahmood2014"/><ref name=Brosnick2014/><ref name=Acta2013>{{cite journal | vauthors = Melnik BC, John SM, Plewig G | title = Acne: risk indicator for increased body mass index and insulin resistance | journal = Acta Dermato-Venereologica | volume = 93 | issue = 6 | pages = 644–9 | date = November 2013 | pmid = 23975508 | doi = 10.2340/00015555-1677 | type = Review | doi-access = free }}</ref> Multiple [[randomized controlled trial]]s and nonrandomized studies have found a lower-glycemic-load diet to be effective in reducing acne.<ref name=Brosnick2014/> There is weak observational evidence suggesting that dairy milk consumption is positively associated with a higher frequency and severity of acne.<ref name=Bhate2014/><ref name=Brosnick2014>{{cite journal | vauthors = Bronsnick T, Murzaku EC, Rao BK | title = Diet in dermatology: Part I. Atopic dermatitis, acne, and nonmelanoma skin cancer | journal = Journal of the American Academy of Dermatology | volume = 71 | issue = 6 | pages = 1039.e1–1039.e12 | date = December 2014 | pmid = 25454036 | doi = 10.1016/j.jaad.2014.06.015 | type = Review }}</ref><ref name="Davidovici2010">{{cite journal|vauthors=Davidovici BB, Wolf R|date=January 2010|title=The role of diet in acne: facts and controversies|journal=Clinics in Dermatology|type=Review|volume=28|issue=1|pages=12–6|doi=10.1016/j.clindermatol.2009.03.010|pmid=20082944}}</ref><ref name=Diet2010>{{cite journal | vauthors = Ferdowsian HR, Levin S | title = Does diet really affect acne? | journal = Skin Therapy Letter | volume = 15 | issue = 3 | pages = 1–2, 5 | date = March 2010 | pmid = 20361171 | url = http://www.skintherapyletter.com/2010/15.3/1.html | url-status = live | type = Review | archive-url = https://web.archive.org/web/20150221185238/http://www.skintherapyletter.com/2010/15.3/1.html | archive-date = 21 February 2015 }}</ref><ref>{{cite book |doi=10.1159/000325580 |chapter=Evidence for Acne-Promoting Effects of Milk and Other Insulinotropic Dairy Products |title=Milk and Milk Products in Human Nutrition |series=Nestlé Nutrition Institute Workshop Series: Pediatric Program |year=2011 |last1=Melnik |first1=Bodo C. |volume=67 |pages=131–145 |pmid=21335995 |isbn=978-3-8055-9587-2 |s2cid=25852903 }}</ref> Milk contains [[whey protein]] and hormones such as bovine IGF-1 and precursors of dihydrotestosterone.<ref name=Brosnick2014/> Studies suggest these components promote the effects of insulin and IGF-1 and thereby increase the production of androgen hormones, sebum, and promote the formation of comedones.<ref name=Brosnick2014/> Available evidence does not support a link between eating chocolate or salt and acne severity.<ref name="Davidovici2010"/><ref name=Diet2010/> Few studies have examined the relationship between [[obesity]] and acne.<ref name="Bhate2013"/> [[Vitamin B12|Vitamin B<sub>12</sub>]] may trigger skin outbreaks similar to acne (acneiform eruptions), or worsen existing acne when taken in doses exceeding the [[recommended daily intake]].<ref>{{cite journal | vauthors = Brescoll J, Daveluy S | title = A review of vitamin B12 in dermatology | journal = American Journal of Clinical Dermatology | volume = 16 | issue = 1 | pages = 27–33 | date = February 2015 | pmid = 25559140 | doi = 10.1007/s40257-014-0107-3 | s2cid = 21580128 | type = Review }}</ref>

=== Stress ===
There are few high-quality studies to demonstrate that stress causes or worsens acne.<ref name=Orion2014>{{cite journal | vauthors = Orion E, Wolf R | title = Psychologic factors in the development of facial dermatoses | journal = Clinics in Dermatology | volume = 32 | issue = 6 | pages = 763–6 | date = November–December 2014 | pmid = 25441469 | doi = 10.1016/j.clindermatol.2014.02.015 | type = Review }}</ref> Despite being controversial, some research indicates that increased acne severity is associated with high stress levels in certain contexts, such as hormonal changes seen in [[premenstrual syndrome]].<ref name=Rodriguez2014>{{cite journal | vauthors = Rodriguez-Vallecillo E, Woodbury-Fariña MA | title = Dermatological manifestations of stress in normal and psychiatric populations | journal = The Psychiatric Clinics of North America | volume = 37 | issue = 4 | pages = 625–51 | date = December 2014 | pmid = 25455069 | doi = 10.1016/j.psc.2014.08.009 | type = Review }}</ref><ref>{{cite web |last1=Garrick |first1=Nancy |title=Acne |url=https://www.niams.nih.gov/health-topics/acne |website=National Institute of Arthritis and Musculoskeletal and Skin Diseases |date=1 September 2016 |access-date=23 July 2021 |archive-date=2 February 2015 |archive-url=https://web.archive.org/web/20150202064933/http://www.niams.nih.gov/health_info/acne/default.asp |url-status=live }}</ref>

=== Other ===
Some individuals experience severe intensification of their acne when they are exposed to hot humid climates; this is due to bacteria and fungus thriving in warm, moist environments. This climate-induced acne exacerbation has been termed [[tropical acne]].
Mechanical obstruction of [[skin follicles]] with helmets or chinstraps can worsen pre-existing acne.<ref name="Basak2013">{{cite journal | vauthors = Basak SA, Zaenglein AL | title = Acne and its management | journal = Pediatrics in Review | volume = 34 | issue = 11 | pages = 479–97 | date = November 2013 | pmid = 24187141 | doi = 10.1542/pir.34-11-479 | type = Review }}</ref> However, acne caused by mechanical obstruction is technically not acne vulgaris, but another [[acneiform eruption]] known as [[acne mechanica]].

Several medications can also worsen pre-existing acne; this condition is the [[acne medicamentosa]] form of acne. Examples of such medications include [[Lithium (medication)|lithium]], [[hydantoin]], [[isoniazid]], [[glucocorticoids]], [[iodides]], [[bromides]], and [[testosterone]].<ref name="FitzAtlas"/> When acne medicamentosa is specifically caused by [[anabolic steroids|anabolic–androgenic steroids]] it can simply be referred to as [[steroid acne]].

Genetically susceptible individuals can get acne breakouts as a result of [[polymorphous light eruption]]; a condition triggered by sunlight and artificial UV light exposure. This form of acne is called [[Acne aestivalis]] and is specifically caused by intense [[Ultraviolet#Subtypes|UVA light]] exposure. Affected individuals usually experience seasonal acne breakouts on their upper arms, shoulder girdle, back, and chest. The breakouts typically occur one-to-three days after exposure to intese UVA radiation. Unlike other forms of acne, the condition spares the face; this could possibly be a result of the pathogenesis of polymorphous light eruption, in which areas of the skin that are ''newly'' exposed to intense ultraviolet radiation are affected. Since faces are typically left uncovered at all stages of life, there is little-to-no likelihood for an eruption to appear there. [[Acne aestivalis#Recent Research|Studies show]] that both polymorphous light eruption outbreaks and the acne aestivalis breakout response can be prevented by topical antioxidants combined with the application of a broad spectrum sunscreen.<ref>{{cite journal |last1=Rippke |first1=F. |last2=Wendt |first2=G. |last3=Bohnsack |first3=K. |last4=Dörschner |first4=A. |last5=Stäb |first5=F. |last6=Hölzle |first6=E. |last7=Moll |first7=I. |title=Results of photoprovocation and field studies on the efficacy of a novel topically applied antioxidant in polymorphous light eruption |journal=Journal of Dermatological Treatment |date=1 January 2001 |volume=12 |issue=1 |pages=3–8 |doi=10.1080/095466301750163491 |pmid=12171679 |s2cid=25658207 }}</ref>