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{{Short description|Skin condition characterized by pimples}} {{About|a skin disease common during adolescence|other acneiform skin diseases|Acne (disambiguation)}} {{Good article}} {{Pp-semi-indef}} {{Pp-move-vandalism|small=yes}} {{cs1 config|name-list-style=vanc}} {{Use dmy dates|date=March 2020}} {{Infobox medical condition | name = Acne | synonyms = Acne vulgaris | image = Acne vulgaris on a very oily skin.jpg | caption = Acne vulgaris in an 18-year-old male during [[puberty]] | alt = Photograph of an 18-year-old male with moderate severity acne vulgaris demonstrating classic features of whiteheads and oily skin distributed over the forehead | field = [[Dermatology]] | symptoms = [[comedo|Blackheads, whiteheads]], [[pimple]]s, oily skin, [[scar]]ring<ref name="Vary2015" /><ref name="Bhate2013" /> | complications = [[anxiety (mood)|Anxiety]], reduced [[self-esteem]], [[clinical depression|depression]], [[suicidal ideations|thoughts of suicide]]<ref name=Barnes2012/><ref name=Goodman2006/> | onset = [[Puberty]]<ref name="NEJM2005" /> | duration = | causes = | risks = [[Genetics]]<ref name="Bhate2013" /> | diagnosis = | differential = [[Folliculitis]], [[rosacea]], [[hidradenitis suppurativa]], [[miliaria]]<ref>{{cite book |last1=Kahan |first1=Scott |title=In a Page: Medicine|date=2008|publisher=Lippincott Williams & Wilkins|isbn=9780781770354|page=412|url=https://books.google.com/books?id=46wpAUhUHjMC&pg=PA412 |url-status=live|archive-url=https://web.archive.org/web/20170906210844/https://books.google.com/books?id=46wpAUhUHjMC&pg=PA412|archive-date=6 September 2017}}</ref> | prevention = | treatment = Lifestyle changes, medications, medical procedures<ref name="Mahmood2014" /><ref name="Titus2012" /> | medication = [[Azelaic acid]], [[benzoyl peroxide]], [[salicylic acid]], [[antibiotics]], [[combined oral contraceptive pill|birth control pills]], [[Ethinylestradiol/cyproterone acetate|co-cyprindiol]], [[retinoids]], [[isotretinoin]]<ref name="Titus2012" /> | prognosis = | frequency = 633 million affected (2015)<ref name="GBD2015Pre" /> | deaths = }} '''Acne''' ({{IPAc-en|ˈ|æ|k|n|i|audio=LL-Q1860 (eng)-Flame, not lame-Acne.wav}} {{respell|AK|nee}}), also known as '''''acne vulgaris''''', is a long-term [[Cutaneous condition|skin condition]] that occurs when [[Keratinocyte|dead skin cells]] and [[Sebum|oil from the skin]] clog [[hair follicle]]s.<ref name="Aslam2015">{{cite journal |vauthors = Aslam I, Fleischer A, Feldman S |title = Emerging drugs for the treatment of acne |journal = Expert Opinion on Emerging Drugs |volume = 20 |issue = 1 |pages = 91–101 |date = March 2015 |pmid = 25474485 |doi = 10.1517/14728214.2015.990373 |s2cid = 12685388 |type = Review | issn = 1472-8214}}{{subscription required}}</ref> Typical features of the condition include [[comedo|blackheads or whiteheads]], [[pimple]]s, oily skin, and possible [[scar]]ring.<ref name="Vary2015">{{cite journal |vauthors = Vary JC |title = Selected Disorders of Skin Appendages--Acne, Alopecia, Hyperhidrosis |journal = The Medical Clinics of North America |volume = 99 |issue = 6 |pages = 1195–211 |date = November 2015 |pmid = 26476248 |doi = 10.1016/j.mcna.2015.07.003 |type = Review }}</ref><ref name="Bhate2013"/><ref>{{cite journal |vauthors = Tuchayi SM, Makrantonaki E, Ganceviciene R, Dessinioti C, Feldman SR, Zouboulis CC |title = Acne vulgaris |journal = Nature Reviews. Disease Primers |volume = 1 |pages = 15033 |date = September 2015 |pmid = 27227877 |doi = 10.1038/nrdp.2015.33 |s2cid = 44167421 |doi-access = free }}</ref> It primarily affects skin with a relatively high number of [[sebaceous gland|oil glands]], including the face, upper part of the chest, and back.<ref name="women">{{cite web |url=https://www.womenshealth.gov/files/assets/docs/fact-sheets/acne.pdf |title=Frequently Asked Questions: Acne |date=July 2009 |publisher=U.S. Department of Health and Human Services, Office of Public Health and Science, Office on Women's Health |access-date=30 July 2009 |url-status=dead |archive-url=https://web.archive.org/web/20161210141821/https://www.womenshealth.gov/files/assets/docs/fact-sheets/acne.pdf |archive-date=10 December 2016}}</ref> The resulting appearance can lead to lack of confidence, [[anxiety (mood)|anxiety]], reduced [[self-esteem]], and, in extreme cases, [[clinical depression|depression]] or [[suicidal ideations|thoughts of suicide]].<ref name="Barnes2012">{{cite journal |vauthors = Barnes LE, Levender MM, Fleischer AB, Feldman SR |title = Quality of life measures for acne patients |journal = Dermatologic Clinics |volume = 30 |issue = 2 |pages = 293–300, ix |date = April 2012 |pmid = 22284143 |doi = 10.1016/j.det.2011.11.001 |type = Review }}</ref><ref name="Goodman2006">{{cite journal |last1=Goodman |first1=Greg |title=Acne and acne scarring – the case for active and early intervention. |journal=Australian Family Physician |date=July 2006 |volume=35 |issue=7 |pages=503–504 |pmid=16820822 |url=https://www.racgp.org.au/afp/200607/8194 |access-date=16 April 2022 |archive-date=19 April 2022 |archive-url=https://web.archive.org/web/20220419115433/https://www.racgp.org.au/afp/200607/8194 |url-status=live }}</ref> Susceptibility to acne is primarily genetic in 80% of cases.<ref name="Bhate2013">{{cite journal | vauthors = Bhate K, Williams HC | title = Epidemiology of acne vulgaris | journal = The British Journal of Dermatology | volume = 168 | issue = 3 | pages = 474–85 | date = March 2013 | pmid = 23210645 | doi = 10.1111/bjd.12149 | s2cid = 24002879 | type = Review | doi-access = }}</ref> The roles of diet and [[cigarette smoking]] in the condition are unclear, and neither [[hygiene|cleanliness]] nor exposure to sunlight are associated with acne.<ref name="Bhate2013"/><ref name="Knutsen2012">{{cite journal | vauthors = Knutsen-Larson S, Dawson AL, Dunnick CA, Dellavalle RP | title = Acne vulgaris: pathogenesis, treatment, and needs assessment | journal = Dermatologic Clinics | volume = 30 | issue = 1 | pages = 99–106, viii-ix | date = January 2012 | pmid = 22117871 | doi = 10.1016/j.det.2011.09.001 | type = Review }}</ref><ref name="Schnopp2011">{{cite journal | vauthors = Schnopp C, Mempel M | title = Acne vulgaris in children and adolescents | journal = Minerva Pediatrica | volume = 63 | issue = 4 | pages = 293–304 | date = August 2011 | pmid = 21909065 | type = Review }}</ref> In both [[sex]]es, [[hormone]]s called [[androgen]]s appear to be part of the underlying mechanism, by causing increased production of [[sebum]].<ref name=NEJM2005>{{cite journal | vauthors = James WD | title = Clinical practice. Acne | journal = The New England Journal of Medicine | volume = 352 | issue = 14 | pages = 1463–72 | date = April 2005 | pmid = 15814882 | doi = 10.1056/NEJMcp033487 | type = Review }}</ref> Another common factor is the excessive growth of the bacterium ''[[Cutibacterium acnes]]'', which is present on the skin.<ref name="Zaenglein2018"/> Treatments for acne are available, including lifestyle changes, medications, and medical procedures. Eating fewer [[monosaccharide|simple carbohydrates]] such as [[sugar]] may minimize the condition.<ref name="Mahmood2014">{{cite journal | vauthors = Mahmood SN, Bowe WP | title = [Diet and acne update: carbohydrates emerge as the main culprit] | url = https://jddonline.com/articles/dermatology/S1545961614P0428X | journal = [[Journal of Drugs in Dermatology]] | volume = 13 | issue = 4 | pages = 428–35 | date = April 2014 | pmid = 24719062 | type = Review | access-date = 3 September 2020 | archive-date = 11 August 2020 | archive-url = https://web.archive.org/web/20200811185258/https://jddonline.com/articles/dermatology/S1545961614P0428X | url-status = live }}</ref> [[Topical medication|Treatments applied directly to the affected skin]], such as [[azelaic acid]], [[benzoyl peroxide]], and [[salicylic acid]], are commonly used.<ref name=Titus2012/> [[Antibiotics]] and [[retinoids]] are available in [[Pharmaceutical formulation|formulations]] that are applied to the skin and [[Route of administration#Oral|taken by mouth]] for the treatment of acne.<ref name=Titus2012/> However, [[antimicrobial resistance|resistance to antibiotics]] may develop as a result of antibiotic therapy.<ref name="ReferenceA">{{cite journal | vauthors = Beylot C, Auffret N, Poli F, Claudel JP, Leccia MT, Del Giudice P, Dreno B | title = Propionibacterium acnes: an update on its role in the pathogenesis of acne | journal = Journal of the European Academy of Dermatology and Venereology | volume = 28 | issue = 3 | pages = 271–8 | date = March 2014 | pmid = 23905540 | doi = 10.1111/jdv.12224 | s2cid = 26027411 | type = Review | doi-access = free }}</ref> Several types of [[combined oral contraceptive pill|birth control pills]] help prevent acne in women.<ref name=Titus2012/> Medical professionals typically reserve [[isotretinoin]] pills for severe acne, due to greater potential side effects.<ref name="Titus2012">{{cite journal |last1=Titus |first1=Stephen |last2=Hodge |first2=Joshua |title=Diagnosis and Treatment of Acne |journal=American Family Physician |date=15 October 2012 |volume=86 |issue=8 |pages=734–740 |pmid=23062156 |url=https://www.aafp.org/afp/2012/1015/p734.html |access-date=16 April 2022 |archive-date=18 February 2015 |archive-url=https://web.archive.org/web/20150218104435/http://www.aafp.org/afp/2012/1015/p734.html |url-status=live }}</ref><ref name="Lew2018">{{cite journal | vauthors = Vallerand IA, Lewinson RT, Farris MS, Sibley CD, Ramien ML, Bulloch AG, Patten SB | title = Efficacy and adverse events of oral isotretinoin for acne: a systematic review | journal = The British Journal of Dermatology | volume = 178 | issue = 1 | pages = 76–85 | date = January 2018 | pmid = 28542914 | doi = 10.1111/bjd.15668 | s2cid = 635373 }}</ref> Early and aggressive treatment of acne is advocated by some in the medical community to decrease the overall long-term impact on individuals.<ref name=Goodman2006/> In 2015, acne affected approximately 633{{nbsp}}million people globally, making it the eighth-most common disease worldwide.<ref name=GBD2015Pre>{{cite journal | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 | author1 = ((GBD 2015 Disease Injury Incidence Prevalence Collaborators)) }}</ref><ref name=Hay2013>{{cite journal | vauthors = Hay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP, Margolis DJ, Marks R, Naldi L, Weinstock MA, Wulf SK, Michaud C, Murray C, Naghavi M | display-authors = 6 | title = The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions | journal = The Journal of Investigative Dermatology | volume = 134 | issue = 6 | pages = 1527–1534 | date = June 2014 | pmid = 24166134 | doi = 10.1038/jid.2013.446 | doi-access = free }}</ref> Acne commonly occurs in [[adolescence]] and affects an estimated 80–90% of teenagers in the [[Western world]].<ref name="Taylor2011">{{cite journal | vauthors = Taylor M, Gonzalez M, Porter R | title = Pathways to inflammation: acne pathophysiology | journal = European Journal of Dermatology | volume = 21 | issue = 3 | pages = 323–33 | date = May–June 2011 | pmid = 21609898 | doi = 10.1684/ejd.2011.1357 | s2cid = 7128254 | type = Review }}</ref><ref name="BMJ2013">{{cite journal | vauthors = Dawson AL, Dellavalle RP | title = Acne vulgaris | journal = The BMJ | volume = 346 | issue = 5 | pages = 30–33 | date = May 2013 | pmid = 23657180 | doi = 10.1136/bmj.f2634 | type = Review | jstor = 23494950 | s2cid = 5331094 }}</ref><ref name="Goldberg2011">{{cite book| vauthors = Goldberg DJ, Berlin AL |title=Acne and Rosacea: Epidemiology, Diagnosis and Treatment|publisher=Manson Pub.|location=London|isbn=978-1-84076-150-4|page=8|url=https://books.google.com/books?id=ZSjauawI1FsC&pg=PA8|date=October 2011|url-status=live|archive-url=https://web.archive.org/web/20160702231501/https://books.google.com/books?id=ZSjauawI1FsC&pg=PA8&dq|archive-date=2 July 2016}}</ref> Some rural societies report lower rates of acne than industrialized ones.<ref name=Goldberg2011/><ref name="Spen2009">{{cite journal | vauthors = Spencer EH, Ferdowsian HR, Barnard ND | title = Diet and acne: a review of the evidence | journal = International Journal of Dermatology | volume = 48 | issue = 4 | pages = 339–47 | date = April 2009 | pmid = 19335417 | doi = 10.1111/j.1365-4632.2009.04002.x | s2cid = 16534829 | type = Review | doi-access = }}</ref> Children and adults may also be affected before and after puberty.<ref name="ReferenceB">{{cite journal | vauthors = Admani S, Barrio VR | title = Evaluation and treatment of acne from infancy to preadolescence | journal = Dermatologic Therapy | volume = 26 | issue = 6 | pages = 462–6 | date = November 2013 | pmid = 24552409 | doi = 10.1111/dth.12108 | s2cid = 30549586 | type = Review | doi-access = free }}</ref> Although acne becomes less common in adulthood, it persists in nearly half of affected people into their twenties and thirties, and a smaller group continues to have difficulties in their forties.<ref name=Bhate2013/> {{TOC limit|3}} ==Classification== The severity of acne vulgaris (Gr. ἀκμή, "point" + L. ''vulgaris'', "common")<ref>{{cite encyclopedia |title="acne", "vulgar" |encyclopedia=Oxford English Dictionary |edition = 2nd |year= 2009 |medium=CD-ROM |publisher=Oxford University Press |location=Oxford}}</ref> can be classified as mild, moderate, or severe to determine an appropriate treatment regimen.<ref name="BMJ2013"/> There is no universally accepted scale for grading acne severity.<ref name="Zaenglein2018"/> The presence of clogged skin follicles (known as [[comedo]]nes) limited to the face with occasional inflammatory lesions defines mild acne.<ref name=BMJ2013/> Moderate severity acne is said to occur when a higher number of inflammatory [[papule]]s and [[pustule]]s occur on the face, compared to mild cases of acne, and appear on the trunk of the body.<ref name=BMJ2013/> Severe acne is said to occur when [[Nodule (dermatology)|nodules]] (the painful 'bumps' lying under the skin) are the characteristic facial lesions, and involvement of the trunk is extensive.<ref name=BMJ2013/><ref name=Fitzpatrick2012/> The lesions are usually polymorphic, meaning they can take many forms, including open or closed comedones (commonly known as blackheads and whiteheads), papules, pustules, and even nodules or cysts so that these lesions often leave behind sequelae, or abnormal conditions resulting from a previous disease, such as scarring or hyperpigmentation.<ref name="pmid38650835"/> Large nodules were previously called [[cyst]]s. The term ''nodulocystic'' has been used in the medical literature to describe severe cases of inflammatory acne.<ref name=Fitzpatrick2012>{{cite book| vauthors = Zaenglein AL, Graber EM, Thiboutot DM |year=2012|chapter=Chapter 80 Acne Vulgaris and Acneiform Eruptions|editor=Goldsmith, Lowell A. |editor2=Katz, Stephen I. |editor3=Gilchrest, Barbara A. |editor4=Paller, Amy S. |editor5=Lefell, David J. |editor6=Wolff, Klaus |title=Fitzpatrick's Dermatology in General Medicine|edition=8th|location=New York |publisher=McGraw-Hill|isbn=978-0-07-171755-7|pages=897–917}}</ref> True cysts are rare in those with acne, and the term ''severe nodular acne'' is now the preferred terminology.<ref name=Fitzpatrick2012/> ''Acne inversa'' (L. invertō, "upside-down") and ''acne rosacea'' (rosa, "rose-colored" + -āceus, "forming") are not forms of acne and are alternate names that respectively refer to the skin conditions [[hidradenitis suppurativa]] (HS) and [[rosacea]].<ref name="Dessinioti2014">{{cite journal | vauthors = Dessinioti C, Katsambas A, Antoniou C | title = Hidradenitis suppurrativa (acne inversa) as a systemic disease | journal = Clinics in Dermatology | volume = 32 | issue = 3 | pages = 397–408 | date = May–June 2014 | pmid = 24767187 | doi = 10.1016/j.clindermatol.2013.11.006 | type = Review }}</ref><ref name="Moustafa2014">{{cite journal | vauthors = Moustafa FA, Sandoval LF, Feldman SR | title = Rosacea: new and emerging treatments | journal = Drugs | volume = 74 | issue = 13 | pages = 1457–65 | date = September 2014 | pmid = 25154627 | doi = 10.1007/s40265-014-0281-x | s2cid = 5205305 | type = Review }}</ref><ref name="Dessinioti2014B">{{cite journal | vauthors = Dessinioti C, Antoniou C, Katsambas A | title = Acneiform eruptions | journal = Clinics in Dermatology | volume = 32 | issue = 1 | pages = 24–34 | date = January–February 2014 | pmid = 24314375 | doi = 10.1016/j.clindermatol.2013.05.023 | type = Review }}</ref> Although HS shares certain overlapping features with acne vulgaris, such as a tendency to clog skin follicles with skin cell debris, the condition otherwise lacks the hallmark features of acne and is therefore considered a distinct skin disorder.<ref name="Dessinioti2014"/> ==Signs and symptoms== {{multiple image | direction = vertical | align = right | image1 = Cysticacne-cropped.jpg | caption1 = A severe case of nodular acne | alt1 = A photograph of a human face with nodular acne | image2 = Backacne.JPG | caption2 = Nodular acne on the back | alt2 = A photograph of a human back with nodular acne | image3 = Teenager with acne.jpg | caption3 = A typical case of a teenager with acne, pimples in various parts of the head | alt3 = Acne pimples can appear in any part of the head; severity and position differs in each person. }} Typical features of acne include [[Sebaceous gland#Clinical significance|increased secretion]] of oily [[sebum]] by the skin, microcomedones, comedones, papules, nodules (large papules), pustules, and often results in scarring.<ref name=Adi2009>{{cite journal | vauthors = Adityan B, Kumari R, Thappa DM | title = Scoring systems in acne vulgaris | journal = Indian Journal of Dermatology, Venereology and Leprology | volume = 75 | issue = 3 | pages = 323–6 | date = May 2009 | pmid = 19439902 | doi = 10.4103/0378-6323.51258 | url = https://tspace.library.utoronto.ca/bitstream/1807/48422/1/dv09103.pdf | type = Review | doi-access = free | access-date = 5 September 2019 | archive-date = 27 August 2021 | archive-url = https://web.archive.org/web/20210827203255/https://tspace.library.utoronto.ca/bitstream/1807/48422/1/dv09103.pdf | url-status = live }}</ref><ref name=Zhao2012/> The appearance of acne varies with skin color. It may result in psychological and social problems.<ref name=BMJ2013/> ===Scars=== Acne [[scar]]s are caused by [[inflammation]] within the [[dermis]] and are estimated to affect 95% of people with acne vulgaris.<ref name="Fife2016">{{cite journal | vauthors = Fife D | title = Evaluation of Acne Scars: How to Assess Them and What to Tell the Patient | journal = Dermatologic Clinics | volume = 34 | issue = 2 | pages = 207–13 | date = April 2016 | pmid = 27015781 | doi = 10.1016/j.det.2015.11.009 | type = Review }}</ref> Abnormal healing and dermal inflammation create the scar.<ref name=Levy2012>{{cite journal | vauthors = Levy LL, Zeichner JA | title = Management of acne scarring, part II: a comparative review of non-laser-based, minimally invasive approaches | journal = American Journal of Clinical Dermatology | volume = 13 | issue = 5 | pages = 331–40 | date = October 2012 | pmid = 22849351 | doi = 10.2165/11631410-000000000-00000 | s2cid = 41448330 | type = Review }}</ref> Scarring is most likely to take place with severe acne but may occur with any form of acne vulgaris.<ref name="Fife2016"/> Acne scars are classified based on whether the abnormal healing response following dermal inflammation leads to excess [[collagen]] deposition or loss at the site of the acne lesion.<ref name="Sanchez2015">{{cite journal | vauthors = Sánchez Viera M | title = Management of acne scars: fulfilling our duty of care for patients | journal = The British Journal of Dermatology | volume = 172 Suppl 1 | issue = Supplement 1 | pages = 47–51 | date = July 2015 | pmid = 25597636 | doi = 10.1111/bjd.13650 | type = Review }}</ref> Atrophic acne scars have lost collagen from the healing response and are the most common type of acne scar (accounting for approximately 75% of all acne scars).<ref name=Levy2012/><ref name="Sanchez2015"/> Ice-pick scars, boxcar scars, and rolling scars are subtypes of atrophic acne scars.<ref name="Fife2016"/> Boxcar scars are round or ovoid indented scars with sharp borders and vary in size from 1.5–4 mm across.<ref name=Levy2012/> Ice-pick scars are narrow (less than 2 [[Millimeter|mm]] across), deep scars that extend into the dermis.<ref name=Levy2012/> Rolling scars are broader than ice-pick and boxcar scars (4–5 mm across) and have a wave-like pattern of depth in the skin.<ref name=Levy2012/> [[Hypertrophic scar]]s are uncommon and are characterized by increased collagen content after the abnormal healing response.<ref name=Levy2012/> They are described as firm and raised from the skin.<ref name=Levy2012/><ref name=Sobanko2012>{{cite journal | vauthors = Sobanko JF, Alster TS | title = Management of acne scarring, part I: a comparative review of laser surgical approaches | journal = American Journal of Clinical Dermatology | volume = 13 | issue = 5 | pages = 319–30 | date = October 2012 | pmid = 22612738 | doi = 10.2165/11598910-000000000-00000 | s2cid = 28374672 | type = Review }}</ref> Hypertrophic scars remain within the original margins of the wound, whereas [[keloid|keloid scars]] can form scar tissue outside of these borders.<ref name=Levy2012/> Keloid scars from acne occur more often in men and people with darker skin, and usually occur on the trunk of the body.<ref name=Levy2012/> ===Pigmentation=== After an inflamed nodular acne lesion resolves, it is common for [[Postinflammatory hyperpigmentation|the skin to darken]] in that area, which is known as [[postinflammatory hyperpigmentation]] (PIH). The inflammation stimulates specialized pigment-producing skin cells (known as [[melanocyte]]s) to produce more [[melanin]] pigment, which leads to the skin's darkened appearance.<ref name="Chandra2012"/> PIH occurs more frequently in people with [[Fitzpatrick scale|darker skin color]].<ref name=Yin2014/> Pigmented scar is a common term used for PIH, but is misleading as it suggests the color change is permanent. Often, PIH can be prevented by avoiding any aggravation of the nodule and can fade with time. However, untreated PIH can last for months, years, or even be permanent if deeper layers of skin are affected.<ref name="Callender2011">{{cite journal | vauthors = Callender VD, St Surin-Lord S, Davis EC, Maclin M | title = Postinflammatory hyperpigmentation: etiologic and therapeutic considerations | journal = American Journal of Clinical Dermatology | volume = 12 | issue = 2 | pages = 87–99 | date = April 2011 | pmid = 21348540 | doi = 10.2165/11536930-000000000-00000 | s2cid = 9997519 | type = Review }}</ref> Even minimal skin exposure to the sun's [[ultraviolet radiation|ultraviolet rays]] can sustain hyperpigmentation.<ref name="Chandra2012">{{cite journal | vauthors = Chandra M, Levitt J, Pensabene CA | title = Hydroquinone therapy for post-inflammatory hyperpigmentation secondary to acne: not just prescribable by dermatologists | journal = Acta Dermato-Venereologica | volume = 92 | issue = 3 | pages = 232–5 | date = May 2012 | pmid = 22002814 | doi = 10.2340/00015555-1225 | type = Review | doi-access = free }}</ref> Daily use of [[Sun protection factor|SPF]] 15 or higher [[sunscreen]] can minimize such a risk.<ref name="Callender2011" /> Whitening agents like [[azelaic acid]], [[arbutin]] or else may be used to improve hyperpigmentation.<ref>{{cite journal |last1=Liyanage |first1=Achala |last2=Liyanage |first2=Gayani |last3=Sirimanna |first3=Ganga |last4=Schürer |first4=Nanna |date=February 2022 |title=Comparative Study on Depigmenting Agents in Skin of Color |journal=The Journal of Clinical and Aesthetic Dermatology |volume=15 |issue=2 |pages=12–17 |issn=1941-2789 |pmc=8884189 |pmid=35309879}}</ref> == 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 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> ==Pathophysiology== [[File:Comedo.png|thumb|upright=1.3|Simplistic representation of the formation of acne comedones]] [[File:Blausen 0811 SkinPores.png|thumb|upright=1.3|Hair follicle anatomy demonstrating a healthy hair follicle (pictured left), a whitehead or closed comedo (middle picture), and a blackhead or open comedo (pictured right)|alt=Three images illustrating hair follicle anatomy]] [[File:Acne Pathogenesis Medscape.png|thumb|upright=1.3|Flowchart of the pathological sequence of events leading to acne|alt=Image illustrating a flowchart of the pathophysiology of acne]] Acne vulgaris is a chronic skin disease of the [[pilosebaceous unit]] and develops due to blockages in the skin's [[hair follicle]]s.<ref name=Simonart2013/> Traditionally seen as a disease of adolescence, acne vulgaris is also observed in adults, including post-menopausal women. Acne vulgaris manifested in adult female is called ''adult female acne'' (AFA), defined as a chronic inflammatory disease of the pilosebaceous unit.<ref name="pmid38650835">{{cite journal |vauthors=Dias da Rocha MA, Saint Aroman M, Mengeaud V, Carballido F, Doat G, Coutinho A, Bagatin E |title=Unveiling the Nuances of Adult Female Acne: A Comprehensive Exploration of Epidemiology, Treatment Modalities, Dermocosmetics, and the Menopausal Influence |journal=Int J Womens Health |volume=16 |pages=663–678 |date=2024 |pmid=38650835 |pmc=11034510 |doi=10.2147/IJWH.S431523|doi-access=free }}</ref> Particularly in AFA, during the menopausal transition, a relative increase in androgen levels occurs as estrogen levels begin to decline, so that this hormonal shift can manifest as acne; while most women with AFA exhibit few acne lesions and have normal androgen levels, baseline investigations, including an androgen testing panel, can help rule out associated comorbidities such as [[polycystic ovarian syndrome]], [[congenital adrenal hyperplasia]], or tumors.<ref name="pmid38650835"/> The blockages in the skin's [[hair follicle]]s that cause acne vulgaris manifestations occur as a result of the following four abnormal processes: increased oily [[sebum]] production (influenced by [[androgen]]s), [[Hyperkeratinization|excessive deposition of the protein keratin]] leading to comedo formation, colonization of the follicle by ''Cutibacterium acnes'' (''C. acnes'') bacteria, and the local release of pro-inflammatory chemicals in the skin.<ref name=Simonart2013>{{cite journal | vauthors = Simonart T | title = Immunotherapy for acne vulgaris: current status and future directions | journal = American Journal of Clinical Dermatology | volume = 14 | issue = 6 | pages = 429–35 | date = December 2013 | pmid = 24019180 | doi = 10.1007/s40257-013-0042-8 | s2cid = 37750291 | type = Review }}</ref> The earliest pathologic change is the formation of a plug (a [[Blackhead|microcomedone]]), which is driven primarily by excessive growth, reproduction, and accumulation of [[keratinocyte|skin cells]] in the hair follicle.<ref name=Vary2015/> In healthy skin, the skin cells that have died come up to the surface and exit the pore of the hair follicle.<ref name="Aslam2015"/> In people with acne, the increased production of oily sebum causes the dead skin cells to stick together.<ref name="Aslam2015"/> The accumulation of dead skin cell debris and oily sebum blocks the pore of the hair follicle, thus forming the microcomedone.<ref name="Aslam2015"/> The ''C. acnes'' [[biofilm]] within the hair follicle worsens this process.<ref name=Das2014/> If the microcomedone is superficial within the hair follicle, the skin pigment [[melanin]] is exposed to air, resulting in its [[oxidation]] and dark appearance (known as a blackhead or open comedo).<ref name=Vary2015/><ref name="Aslam2015"/><ref name=BMJ2013/> In contrast, if the microcomedone occurs deep within the hair follicle, this causes the formation of a whitehead (known as a closed comedo).<ref name=Vary2015/><ref name="Aslam2015"/> The main hormonal driver of oily sebum production in the skin is [[dihydrotestosterone]].<ref name=Vary2015/> Another androgenic hormone responsible for increased sebaceous gland activity is [[Dehydroepiandrosterone|DHEA-S]]. The [[adrenal gland]]s secrete higher amounts of DHEA-S during [[adrenarche]] (a stage of [[puberty]]), and this leads to an increase in sebum production. In a sebum-rich skin environment, the naturally occurring and largely [[commensal]] skin bacterium ''C. acnes'' readily grows and can cause [[inflammation]] within and around the follicle due to activation of the [[innate immune system]].<ref name="Aslam2015"/> ''C. acnes'' triggers skin inflammation in acne by increasing the production of several pro-inflammatory [[cytokine|chemical signals]] (such as [[IL-1α]], [[Interleukin 8|IL-8]], [[TNF-α]], and LTB4); IL-1α is essential to comedo formation.<ref name=Das2014>{{cite journal | vauthors = Das S, Reynolds RV | title = Recent advances in acne pathogenesis: implications for therapy | journal = American Journal of Clinical Dermatology | volume = 15 | issue = 6 | pages = 479–88 | date = December 2014 | pmid = 25388823 | doi = 10.1007/s40257-014-0099-z | s2cid = 28243535 | type = Review }}</ref> ''C. acnes''' ability to bind and activate a class of [[immune system]] receptors known as [[toll-like receptor]]s (TLRs), especially [[toll-like receptor 2|TLR2]] and [[toll-like receptor 4|TLR4]], is a core mechanism of acne-related skin inflammation.<ref name=Das2014/><ref name=Andriessen2014>{{cite journal | vauthors = Andriessen A, Lynde CW | title = Antibiotic resistance: shifting the paradigm in topical acne treatment | journal = Journal of Drugs in Dermatology | volume = 13 | issue = 11 | pages = 1358–64 | date = November 2014 | pmid = 25607703 | type = Review }}</ref><ref name=Hammer2015>{{cite journal | vauthors = Hammer KA | title = Treatment of acne with tea tree oil (melaleuca) products: a review of efficacy, tolerability and potential modes of action | journal = International Journal of Antimicrobial Agents | volume = 45 | issue = 2 | pages = 106–10 | date = February 2015 | pmid = 25465857 | doi = 10.1016/j.ijantimicag.2014.10.011 | type = Review }}</ref> Activation of TLR2 and TLR4 by ''C. acnes'' leads to increased secretion of IL-1α, IL-8, and TNF-α.<ref name=Das2014/> The release of these inflammatory signals attracts various immune cells to the hair follicle, including [[neutrophil]]s, [[macrophage]]s, and [[Th1 cell]]s.<ref name=Das2014/> IL-1α stimulates increased skin cell activity and reproduction, which, in turn, fuels comedo development.<ref name=Das2014/> Furthermore, sebaceous gland cells produce more [[antimicrobial peptides]], such as [[Defensin, beta 1|HBD1]] and [[Beta-defensin 2|HBD2]], in response to the binding of TLR2 and TLR4.<ref name=Das2014/> ''C. acnes'' also provokes skin inflammation by altering the fatty composition of oily sebum.<ref name=Das2014/> Oxidation of the [[lipid]] [[squalene]] by ''C. acnes'' is of particular importance. Squalene oxidation activates [[NF-κB]] (a protein complex) and consequently increases IL-1α levels.<ref name=Das2014/> Additionally, squalene oxidation increases [[5-lipoxygenase]] enzyme activity, which catalyzes the conversion of [[arachidonic acid]] to [[leukotriene B4]] (LTB4).<ref name=Das2014/> LTB4 promotes skin inflammation by acting on the [[peroxisome proliferator-activated receptor alpha]] (PPARα) protein.<ref name=Das2014/> PPARα increases the activity of [[activator protein 1]] (AP-1) and NF-κB, thereby leading to the recruitment of inflammatory [[T cell]]s.<ref name=Das2014/> ''C. acnes''' ability to convert sebum [[triglyceride]]s to pro-inflammatory [[free fatty acid]]s via secretion of the enzyme [[lipase]] further explains its inflammatory properties.<ref name=Das2014/> These free fatty acids spur increased production of [[cathelicidin]], HBD1, and HBD2, thus leading to further inflammation.<ref name=Das2014/> This inflammatory cascade typically leads to the formation of inflammatory acne lesions, including [[papule]]s, infected [[pustule]]s, or [[nodule (medicine)|nodules]].<ref name=Vary2015/> If the inflammatory reaction is severe, the follicle can break into the deeper layers of the dermis and [[subcutaneous tissue]] and cause the formation of deep nodules.<ref name=Vary2015/><ref name=Sieber2014>{{cite journal | vauthors = Sieber MA, Hegel JK | title = Azelaic acid: Properties and mode of action | journal = Skin Pharmacology and Physiology | volume = 27 Suppl 1 | issue = Supplement 1 | pages = 9–17 | date = November 2013 | pmid = 24280644 | doi = 10.1159/000354888 | s2cid = 8848543 | type = Review }}</ref><ref name=Simpson2004>{{cite book |last1=Simpson|first1=Nicholas B.|last2=Cunliffe|first2=William J. |year=2004 |chapter=Disorders of the sebaceous glands |pages=431–75|editor=Burns, Tony|editor2=Breathnach, Stephen |editor3=Cox, Neil |editor4=Griffiths, Christopher |title=Rook's textbook of dermatology |edition=7th |location=Malden, Mass. |publisher=Blackwell Science |isbn=978-0-632-06429-8}}</ref> The involvement of AP-1 in the aforementioned inflammatory cascade activates [[matrix metalloproteinase]]s, which contribute to local tissue destruction and scar formation.<ref name=Das2014/> Along with the bacteria ''C. acnes'', the bacterial species ''Staphylococcus epidermidis'' (''S. epidermidis'') also takes a part in the physiopathology of acne vulgaris. The proliferation of ''S. epidermidis'' with ''C. acnes'' causes the formation of [[biofilms]], which blocks the hair follicles and pores, creating an [[wikt:anaerobic|anaerobic]] environment under the skin. This enables for increased growth of both ''C. acnes'' and ''S. epidermidis'' under the skin. The proliferation of ''C. acnes'' causes the formation of [[biofilms]] and a [[biofilm matrix]], making it even harder to treat the acne.<ref name=Claudel2019>{{cite journal | vauthors = Claudel V, Auffret N, Leccia MT, Poli F, Corvec S, Dréno B | title = ''Staphylococcus epidermidis'': A potential new player in the physiopathology of acne? | journal = Dermatology | volume = 235 | issue = 4 | pages = 287–94 | date = May 2019 | doi = 10.1159/000499858 | pmid = 31112983 | s2cid = 162170301 | type = Review | doi-access = free }}</ref> == Diagnosis == Acne vulgaris is diagnosed based on a medical professional's clinical judgment.<ref name="Zaenglein2018"/> The evaluation of a person with suspected acne should include taking a detailed medical history about a family history of acne, a review of medications taken, signs or symptoms of excessive production of androgen hormones, cortisol, and growth hormone.<ref name="Zaenglein2018"/> Comedones (blackheads and whiteheads) must be present to diagnose acne. In their absence, an appearance similar to that of acne would suggest a different skin disorder.<ref name="Dessinioti2014B"/> Microcomedones (the precursor to blackheads and whiteheads) are not visible to the naked eye when inspecting the skin and require a [[Microscopy|microscope to be seen]].<ref name="Dessinioti2014B"/> Many features may indicate that a person's acne vulgaris is sensitive to hormonal influences. Historical and physical clues that may suggest hormone-sensitive acne include onset between ages 20 and 30; worsening the week before a woman's period; acne lesions predominantly over the jawline and chin; and inflammatory/nodular acne lesions.<ref name=Vary2015/> Several scales exist to grade the severity of acne vulgaris, but disagreement persists about the ideal one for diagnostic use.<ref name=Tan2013>{{cite journal | vauthors = Tan JK, Jones E, Allen E, Pripotnev S, Raza A, Wolfe B | title = Evaluation of essential clinical components and features of current acne global grading scales | journal = Journal of the American Academy of Dermatology | volume = 69 | issue = 5 | pages = 754–761 | date = November 2013 | pmid = 23972509 | doi = 10.1016/j.jaad.2013.07.029 | type = Review }}</ref><ref name=Chiang2014>{{cite journal | vauthors = Chiang A, Hafeez F, Maibach HI | title = Skin lesion metrics: role of photography in acne | journal = The Journal of Dermatological Treatment | volume = 25 | issue = 2 | pages = 100–5 | date = April 2014 | pmid = 23758271 | doi = 10.3109/09546634.2013.813010 | s2cid = 2296120 | type = Review }}</ref> Cook's acne grading scale uses photographs to grade severity from 0 to 8, with higher numbers representing more severe acne. This scale was the first to use a standardized photographic protocol to assess acne severity; since its creation in 1979, the scale has undergone several revisions.<ref name=Chiang2014/> The Leeds acne grading technique counts acne lesions on the face, back, and chest and categorizes them as inflammatory or non-inflammatory. Leeds scores range from 0 (least severe) to 10 (most severe) though modified scales have a maximum score of 12.<ref name=Chiang2014/><ref>{{cite web| vauthors = O' Brien SC, Lewis JB, Cunliffe WJ |title=The Leeds Revised Acne Grading System|url=http://carepathways4gp.org.uk/Acne_Care_Pathway/LEEDS_score_files/Acne%20Grading%20System.pdf|publisher=The Leeds Teaching Hospitals|access-date=23 November 2015|url-status=dead|archive-url=https://web.archive.org/web/20151125021231/http://carepathways4gp.org.uk/Acne_Care_Pathway/LEEDS_score_files/Acne%20Grading%20System.pdf|archive-date=25 November 2015}}</ref> The Pillsbury acne grading scale classifies the severity of the acne from grade 1 (least severe) to grade 4 (most severe).<ref name=Tan2013/><ref name=Purdy2008>{{cite journal | vauthors = Purdy S, Deberker D | title = Acne vulgaris | journal = BMJ Clinical Evidence | volume = 2008 | pages = 1714 | date = May 2008 | pmid = 19450306 | pmc = 2907987 | type = Review }}</ref> ===Differential diagnosis=== Many skin conditions can mimic acne vulgaris, and these are collectively known as [[acneiform eruptions]].<ref name="Dessinioti2014B"/> Such conditions include [[angiofibroma]]s, [[epidermal cyst]]s, [[flat wart]]s, [[folliculitis]], [[keratosis pilaris]], [[milia]], [[perioral dermatitis]], and [[rosacea]], among others.<ref name=BMJ2013/><ref>{{cite journal | vauthors = Del Rosso JQ, Silverberg N, Zeichner JA | title = When Acne is Not Acne | journal = Dermatologic Clinics | volume = 34 | issue = 2 | pages = 225–8 | date = April 2016 | pmid = 27015783 | doi = 10.1016/j.det.2015.12.002 | url = https://touroscholar.touro.edu/tuncom_pubs/13 | type = Review | access-date = 11 July 2019 | archive-date = 27 August 2021 | archive-url = https://web.archive.org/web/20210827203258/https://touroscholar.touro.edu/tuncom_pubs/13/ | url-status = live }}</ref> Age is one factor that may help distinguish between these disorders. Skin disorders such as perioral dermatitis and keratosis pilaris can appear similar to acne but tend to occur more frequently in childhood. Rosacea tends to occur more frequently in older adults.<ref name=BMJ2013/> Facial redness triggered by heat or the consumption of alcohol or spicy food is also more suggestive of rosacea.<ref name=Archer2012>{{cite journal | vauthors = Archer CB, Cohen SN, Baron SE | title = Guidance on the diagnosis and clinical management of acne | journal = Clinical and Experimental Dermatology | volume = 37 Suppl 1 | issue = Supplement 1 | pages = 1–6 | date = May 2012 | pmid = 22486762 | doi = 10.1111/j.1365-2230.2012.04335.x | s2cid = 33276273 | type = Review }}</ref> The presence of comedones helps health professionals differentiate acne from skin disorders that are similar in appearance.<ref name="Titus2012"/> [[Chloracne]] and [[occupational acne]] due to exposure to certain chemicals & industrial compounds, may look very similar to acne vulgaris.<ref>{{cite book|veditors=Kanerva L, Elsner P, Wahlberg JH, Maibach HI |title=Handbook of Occupational Dermatology|date=2013|publisher=Springer Science & Business Media|isbn=978-3-662-07677-4|page=231|url=https://books.google.com/books?id=0DzvCAAAQBAJ&pg=PA231 |url-status=live|archive-url=https://web.archive.org/web/20170906210844/https://books.google.com/books?id=0DzvCAAAQBAJ&pg=PA231|archive-date=6 September 2017}}</ref> ==Management== Many different treatments exist for acne. These include [[alpha hydroxy acid]], anti-androgen medications, antibiotics, antiseborrheic medications, [[azelaic acid]], [[benzoyl peroxide]], [[hormone|hormonal]] treatments, [[keratolytic]] soaps, [[nicotinamide]] (niacinamide), [[retinoids]], and [[salicylic acid]].<ref name=Nurse09/><ref name="pmid38725769">{{cite journal |vauthors=Althwanay A, AlEdani EM, Kaur H, Kasapoglu M, Yadavalli R, Nawaz S, Nath TS |title=Efficacy of Topical Treatments in the Management of Mild-to-Moderate Acne Vulgaris: A Systematic Review |journal=Cureus |volume=16 |issue=4 |pages=e57909 |date=April 2024 |pmid=38725769 |pmc=11081083 |doi=10.7759/cureus.57909|doi-access=free }}</ref> Acne treatments work in at least four different ways, including the following: reducing inflammation, hormonal manipulation, killing ''C. acnes'', and normalizing skin cell shedding and sebum production in the pore to prevent blockage.<ref name="Zaenglein2018"/> Typical treatments include topical therapies such as antibiotics, benzoyl peroxide, and retinoids, and systemic therapies, including antibiotics, hormonal agents, and oral retinoids.<ref name=BMJ2013/><ref name=Simonart2012>{{cite journal | vauthors = Simonart T | title = Newer approaches to the treatment of acne vulgaris | journal = American Journal of Clinical Dermatology | volume = 13 | issue = 6 | pages = 357–64 | date = December 2012 | pmid = 22920095 | doi = 10.2165/11632500-000000000-00000 | s2cid = 12200694 | type = Review }}</ref> Recommended therapies for first-line use in acne vulgaris treatment include topical retinoids, benzoyl peroxide, and topical or oral antibiotics.<ref name="Zaenglein2016"/> Procedures such as light therapy and laser therapy are not first-line treatments and typically have only an [[Adjunctive therapy|add on]] role due to their high cost and limited evidence.<ref name=Simonart2012/> Blue light therapy is of unclear benefit.<ref>{{cite journal | vauthors = Scott AM, Stehlik P, Clark J, Zhang D, Yang Z, Hoffmann T, Mar CD, Glasziou P | display-authors = 6 | title = Blue-Light Therapy for Acne Vulgaris: A Systematic Review and Meta-Analysis | journal = Annals of Family Medicine | volume = 17 | issue = 6 | pages = 545–553 | date = November 2019 | pmid = 31712293 | pmc = 6846280 | doi = 10.1370/afm.2445 | type = Systematic Review & Meta-Analysis | doi-access = free }}</ref> Medications for acne target the early stages of [[comedo]] formation and are generally ineffective for visible skin lesions; acne generally improves between eight and twelve weeks after starting therapy.<ref name="Zaenglein2018"/> People often view acne as a short-term condition, some expecting it to disappear after puberty. This misconception can lead to depending on self-management or problems with long-term adherence to treatment. Communicating the long-term nature of the condition and better access to reliable information about acne can help people know what to expect from treatments.<ref name=":2">{{cite journal |date=2021-06-23 |title=Misconceptions about acne lead to underuse of effective treatments; people need reliable information to manage the condition long-term |url=https://evidence.nihr.ac.uk/alert/misconceptions-acne-lead-to-underuse-effective-treatments-reliable-information-needed/ |journal=NIHR Evidence |type=Plain English summary |doi=10.3310/alert_46654 |s2cid=240655201 |access-date=6 July 2022 |archive-date=22 May 2022 |archive-url=https://web.archive.org/web/20220522103332/https://evidence.nihr.ac.uk/alert/misconceptions-acne-lead-to-underuse-effective-treatments-reliable-information-needed/ |url-status=live }}</ref><ref>{{cite journal |last1=Ip |first1=Athena |last2=Muller |first2=Ingrid |last3=Geraghty |first3=Adam W A |last4=Platt |first4=Duncan |last5=Little |first5=Paul |last6=Santer |first6=Miriam |date=2021-02-01 |title=Views and experiences of people with acne vulgaris and healthcare professionals about treatments: systematic review and thematic synthesis of qualitative research |journal=BMJ Open |volume=11 |issue=2 |pages=e041794 |doi=10.1136/bmjopen-2020-041794 |issn=2044-6055 |pmc=7853035 |pmid=33526498}}</ref> ===Skin care=== In general, it is recommended that people with acne do not wash affected skin more than twice daily.<ref name="Zaenglein2018"/> The application of a fragrance-free [[moisturizer]] to sensitive and acne-prone skin may reduce irritation. Skin irritation from acne medications typically peaks at two weeks after onset of use and tends to improve with continued use.<ref name="Zaenglein2018"/> Dermatologists recommend using cosmetic products that specifically say non-comedogenic, oil-free, and will not clog pores.<ref name="Zaenglein2018"/> Acne vulgaris patients, even those with oily skin,<ref name="Lynde et al 2014">{{cite journal |last1=Lynde |first1=Chuck W. |last2=Andriessen |first2=Anneke |last3=Barankin |first3=Benjamin |last4=Gannes |first4=Gillian De |last5=Gulliver |first5=Wayne |last6=Haber |first6=Richard |last7=Mccuaig |first7=Catherine |last8=Rajan |first8=Poonam |last9=Skotnicki |first9=Sandra P. |last10=Thomas |first10=Richard |last11=Toole |first11=Jack |last12=Vender |first12=Ron |title=Moisturizers and Ceramide-containing Moisturizers May Offer Concomitant Therapy with Benefits |journal=The Journal of Clinical and Aesthetic Dermatology |date=March 2014 |volume=7 |issue=3 |pages=18–26 |pmid=24688622 |pmc=3970828 }}</ref> should moisturize in order to support the skin's moisture barrier since skin barrier dysfunction may contribute to acne.<ref name="Lynde et al 2014"/> Moisturizers, especially [[ceramide]]-containing moisturizers, as an adjunct therapy are particularly helpful for the dry skin and irritation that commonly results from topical acne treatment. Studies show that ceramide-containing moisturizers are important for optimal skin care; they enhance acne therapy adherence and complement existing acne therapies.<ref name="Lynde et al 2014"/> In a study where acne patients used 1.2% clindamycin phosphate / 2.5% benzoyl peroxide gel in the morning and applied a micronized 0.05% tretinoin gel in the evening the overwhelming majority of patients experienced no cutaneous adverse events throughout the study. It was concluded that using ceramide cleanser and ceramide moisturizing cream caused the favorable tolerability, did not interfere with the treatment efficacy, and improved adherence to the regimen.<ref>{{cite journal |last1=Zeichner |first1=Joshua A. |last2=Del Rosso |first2=James Q. |title=Multivesicular Emulsion Ceramide-containing Moisturizers: An Evaluation of Their Role in the Management of Common Skin Disorders |journal=The Journal of Clinical and Aesthetic Dermatology |date=December 2016 |volume=9 |issue=12 |pages=26–32 |pmid=28210396 |pmc=5300724 }}</ref> The importance of preserving the acidic mantle and its barrier functions is widely accepted in the scientific community. Thus, maintaining a pH in the range 4.5 – 5.5 is essential in order to keep the skin surface in its optimal, healthy conditions.<ref>{{cite journal |last1=Ali |first1=Saba M. |last2=Yosipovitch |first2=Gil |title=Skin pH: From Basic SciencE to Basic Skin Care |journal=Acta Dermato-Venereologica |date=2013 |volume=93 |issue=3 |pages=261–267 |doi=10.2340/00015555-1531 |pmid=23322028 |doi-access=free }}</ref><ref>{{cite journal |last1=Prakash |first1=Chaitra |last2=Bhargava |first2=Puneet |last3=Tiwari |first3=Siddhi |last4=Majumdar |first4=Banashree |last5=Bhargava |first5=Rishi Kumar |title=Skin Surface pH in Acne Vulgaris: Insights from an Observational Study and Review of the Literature |journal=The Journal of Clinical and Aesthetic Dermatology |date=July 2017 |volume=10 |issue=7 |pages=33–39 |pmid=29104722 |pmc=5605222 }}</ref><ref>{{cite journal |last1=Schmid-Wendtner |first1=M.-H. |last2=Korting |first2=H.C. |title=The pH of the Skin Surface and Its Impact on the Barrier Function |journal=Skin Pharmacology and Physiology |date=2006 |volume=19 |issue=6 |pages=296–302 |doi=10.1159/000094670 |pmid=16864974 |s2cid=9077120 |url=https://epub.ub.uni-muenchen.de/16348/ |access-date=16 April 2022 |archive-date=19 April 2022 |archive-url=https://web.archive.org/web/20220419115437/https://epub.ub.uni-muenchen.de/16348/ |url-status=live }}</ref><ref>{{cite journal |last1=Lambers |first1=H. |last2=Piessens |first2=S. |last3=Bloem |first3=A. |last4=Pronk |first4=H. |last5=Finkel |first5=P. |title=Natural skin surface pH is on average below 5, which is beneficial for its resident flora |journal=International Journal of Cosmetic Science |date=October 2006 |volume=28 |issue=5 |pages=359–370 |doi=10.1111/j.1467-2494.2006.00344.x |pmid=18489300 |s2cid=25191984 }}</ref><ref>{{cite journal |last1=Proksch |first1=Ehrhardt |title=pH in nature, humans and skin |journal=The Journal of Dermatology |date=September 2018 |volume=45 |issue=9 |pages=1044–1052 |doi=10.1111/1346-8138.14489 |pmid=29863755 |s2cid=44158118 |doi-access=free }}</ref> ===Diet=== [[Causality|Causal]] relationship is rarely observed with diet/nutrition and dermatologic conditions. Rather, associations – some of them compelling – have been found between diet and outcomes including disease severity and the number of conditions experienced by a patient. Evidence is emerging in support of medical nutrition therapy as a way of reducing the severity and incidence of dermatologic diseases, including acne. Researchers observed a link between high glycemic index diets and acne.<ref>{{cite web|title=Medical nutrition therapy shows positive benefits in dermatologic conditions|url=https://www.healio.com/news/dermatology/20200123/medical-nutrition-therapy-shows-positive-benefits-in-dermatologic-conditions|access-date=2021-03-10|website=healio.com|archive-date=12 April 2021|archive-url=https://web.archive.org/web/20210412183745/https://www.healio.com/news/dermatology/20200123/medical-nutrition-therapy-shows-positive-benefits-in-dermatologic-conditions|url-status=live}}</ref> Dermatologists also recommend a [[Low-glycemic diet|diet low in simple sugars]] as a method of improving acne.<ref name=Brosnick2014/> As of 2014, the available evidence is insufficient to use milk restriction for this purpose.<ref name=Brosnick2014/> ===Medications=== ====Benzoyl peroxide==== [[File:Benzoyl peroxide gel.jpg|thumb|upright=1.3|alt=A tube of benzoyl peroxide gel|Benzoyl peroxide cream is a common treatment for acne vulgaris.]] [[Benzoyl peroxide]] (BPO) is a first-line treatment for mild and moderate acne due to its effectiveness and mild side-effects (mainly [[dermatitis|skin irritation]]). In the skin follicle, benzoyl peroxide kills ''C. acnes'' by oxidizing its proteins through the formation of oxygen [[free radical]]s and [[benzoic acid]]. These free radicals likely interfere with the bacterium's metabolism and ability to make proteins.<ref name="Leccia2015">{{cite journal | vauthors = Leccia MT, Auffret N, Poli F, Claudel JP, Corvec S, Dreno B | title = Topical acne treatments in Europe and the issue of antimicrobial resistance | journal = Journal of the European Academy of Dermatology and Venereology | volume = 29 | issue = 8 | pages = 1485–92 | date = August 2015 | pmid = 25677763 | doi = 10.1111/jdv.12989 | s2cid = 12894377 | type = Review }}</ref><ref name="Gamble2012"/> Additionally, benzoyl peroxide is mildly effective at breaking down comedones and inhibiting inflammation.<ref name="Zaenglein2016">{{cite journal | vauthors = Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE, Leyden JJ, Reynolds RV, Silverberg NB, Stein Gold LF, Tollefson MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM, Bhushan R | display-authors = 6 | title = Guidelines of care for the management of acne vulgaris | journal = Journal of the American Academy of Dermatology | volume = 74 | issue = 5 | pages = 945–73.e33 | date = May 2016 | pmid = 26897386 | doi = 10.1016/j.jaad.2015.12.037 | type = Review | doi-access = free }}</ref><ref name="Gamble2012">{{cite journal | vauthors = Gamble R, Dunn J, Dawson A, Petersen B, McLaughlin L, Small A, Kindle S, Dellavalle RP | display-authors = 6 | title = Topical antimicrobial treatment of acne vulgaris: an evidence-based review | journal = American Journal of Clinical Dermatology | volume = 13 | issue = 3 | pages = 141–52 | date = June 2012 | pmid = 22268388 | doi = 10.2165/11597880-000000000-00000 | s2cid = 5838346 | type = Review }}</ref> Combination products use benzoyl peroxide with a topical antibiotic or retinoid, such as [[benzoyl peroxide/clindamycin]] and [[benzoyl peroxide/adapalene]], respectively.<ref name=Yin2014/> Topical benzoyl peroxide is effective at treating acne.<ref>{{cite journal | vauthors = Yang Z, Zhang Y, Lazic Mosler E, Hu J, Li H, Zhang Y, Liu J, Zhang Q | display-authors = 6 | title = Topical benzoyl peroxide for acne | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | pages = CD011154 | date = March 2020 | issue = 3 | pmid = 32175593 | pmc = 7077870 | doi = 10.1002/14651858.CD011154.pub2 | collaboration = Cochrane Skin Group }}</ref> Side effects include increased [[Photosensitivity#Skin reactions|skin photosensitivity]], dryness, redness, and occasional peeling.<ref name=Benz09>{{cite journal | vauthors = Sagransky M, Yentzer BA, Feldman SR | title = Benzoyl peroxide: a review of its current use in the treatment of acne vulgaris | journal = Expert Opinion on Pharmacotherapy | volume = 10 | issue = 15 | pages = 2555–62 | date = October 2009 | pmid = 19761357 | doi = 10.1517/14656560903277228 | s2cid = 26069784 | type = Review }}</ref> Sunscreen use is often advised during treatment, to prevent [[sunburn]]. Lower concentrations of benzoyl peroxide are just as effective as higher concentrations in treating acne but are associated with fewer side effects.<ref name="Gamble2012"/><ref name="Brandstetter2013">{{cite journal | vauthors = Brandstetter AJ, Maibach HI | title = Topical dose justification: benzoyl peroxide concentrations | journal = The Journal of Dermatological Treatment | volume = 24 | issue = 4 | pages = 275–7 | date = August 2013 | pmid = 22103743 | doi = 10.3109/09546634.2011.641937 | s2cid = 7912384 | type = Review }}</ref> Unlike antibiotics, benzoyl peroxide does not appear to generate [[Antimicrobial resistance|bacterial antibiotic resistance]].<ref name=Benz09/> ====Retinoids==== [[Retinoids]] are medications that reduce inflammation, normalize the follicle [[Cell cycle|cell life cycle]], and reduce sebum production.<ref name=Das2014/><ref name="Riahi2016">{{cite journal | vauthors = Riahi RR, Bush AE, Cohen PR | title = Topical Retinoids: Therapeutic Mechanisms in the Treatment of Photodamaged Skin | journal = American Journal of Clinical Dermatology | volume = 17 | issue = 3 | pages = 265–76 | date = June 2016 | pmid = 26969582 | doi = 10.1007/s40257-016-0185-5 | s2cid = 12663356 | type = Review }}</ref> They are structurally related to [[vitamin A]].<ref name="Riahi2016"/> Studies show dermatologists and primary care doctors underprescribe them for acne.<ref name="Zaenglein2018"/> The retinoids appear to influence the cell life cycle in the follicle lining. This helps prevent the [[hyperkeratinization|accumulation of skin cells]] within the hair follicle that can create a blockage. They are a first-line acne treatment,<ref name=Vary2015/> especially for people with dark-colored skin. Retinoids are known to lead to faster improvement of postinflammatory hyperpigmentation.<ref name=Yin2014>{{cite journal | vauthors = Yin NC, McMichael AJ | title = Acne in patients with skin of color: practical management | journal = American Journal of Clinical Dermatology | volume = 15 | issue = 1 | pages = 7–16 | date = February 2014 | pmid = 24190453 | doi = 10.1007/s40257-013-0049-1 | s2cid = 43211448 | type = Review }}</ref> Topical retinoids include [[adapalene]], [[retinol]], [[retinaldehyde]], [[isotretinoin]], [[tazarotene]], [[trifarotene]], and [[tretinoin]].<ref name=Kong2013/><ref name="FDA Snapshot">{{cite web | title=Drug Trials Snapshots: Aklief | website=U.S. [[Food and Drug Administration]] (FDA) | date=11 October 2019 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/drug-trials-snapshots-aklief | archive-url=https://web.archive.org/web/20191119042107/https://www.fda.gov/drugs/resources-information-approved-drugs/drug-trials-snapshots-aklief | archive-date=19 November 2019 | url-status=live | access-date=18 November 2019}}{{PD-notice}}</ref><ref>{{cite web|title=Isotretinoin|url=https://www.drugs.com/international/isotretinoin.html|access-date=2021-04-25|website=Drugs.com|archive-date=16 July 2018|archive-url=https://web.archive.org/web/20180716025017/https://www.drugs.com/international/isotretinoin.html|url-status=live}}</ref> They often cause an initial flare-up of acne and facial [[flushing (physiology)|flushing]] and can cause significant skin irritation. Generally speaking, retinoids increase the skin's [[Photosensitivity|sensitivity to sunlight]] and are therefore recommended for use at night.<ref name=Vary2015/> Tretinoin is the least expensive of the topical retinoids and is the most irritating to the skin, whereas adapalene is the least irritating but costs significantly more.<ref name=Vary2015/><ref name=Foti2015>{{cite journal | vauthors = Foti C, Romita P, Borghi A, Angelini G, Bonamonte D, Corazza M | title = Contact dermatitis to topical acne drugs: a review of the literature | journal = Dermatologic Therapy | volume = 28 | issue = 5 | pages = 323–9 | date = September 2015 | pmid = 26302055 | doi = 10.1111/dth.12282 | s2cid = 43870491 | type = Review | doi-access = free }}</ref> Most formulations of tretinoin are incompatible for use with benzoyl peroxide.<ref name="Zaenglein2018"/> Tazarotene is the most effective and expensive topical retinoid but is usually not as well tolerated.<ref name=Vary2015/><ref name=Foti2015/> In 2019 a tazarotene lotion formulation, marketed to be a less irritating option, was approved by the FDA.<ref>{{cite web|title=Arazlo lotion launched in US for acne treatment|url=https://www.healio.com/news/dermatology/20200623/arazlo-lotion-launched-in-us-for-acne-treatment|access-date=2021-03-10|website=Healio.com|archive-date=28 July 2021|archive-url=https://web.archive.org/web/20210728231130/https://www.healio.com/news/dermatology/20200623/arazlo-lotion-launched-in-us-for-acne-treatment|url-status=live}}</ref> Retinol is a form of vitamin A that has similar but milder effects and is present in many over-the-counter moisturizers and other topical products. Isotretinoin is an oral retinoid that is very effective for severe nodular acne, and moderate acne that is stubborn to other treatments.<ref name="Vary2015" /><ref name="BMJ2013" /> One to two months of use is typically adequate to see improvement. Acne often resolves completely or is much milder after a 4–6 month course of oral isotretinoin.<ref name="Vary2015" /> After a single round of treatment, about 80% of people report an improvement, with more than 50% reporting complete remission.<ref name="BMJ2013" /> About 20% of people require a second course, but 80% of those report improvement, resulting in a cumulative 96% efficacy rate.<ref name="BMJ2013" /> There are concerns that isotretinoin is linked to adverse effects, like [[major depressive disorder|depression]], [[suicidality]], and [[anemia]]. There is no clear evidence to support some of these claims.<ref name="Vary2015" /><ref name="BMJ2013" /> Isotretinoin has been found in some studies to be superior to antibiotics or placebo in reducing acne lesions.<ref name="Lew2018"/> However, a 2018 review comparing inflammatory lesions after treatment with antibiotics or isotretinoin found no difference.<ref>{{cite journal | vauthors = Costa CS, Bagatin E, Martimbianco AL, da Silva EM, Lúcio MM, Magin P, Riera R | title = Oral isotretinoin for acne | journal = The Cochrane Database of Systematic Reviews | volume = 11 | pages = CD009435 | date = November 2018 | issue = 2 | pmid = 30484286 | pmc = 6383843 | doi = 10.1002/14651858.cd009435.pub2 }}</ref> The frequency of adverse events was about twice as high with isotretinoin use, although these were mostly dryness-related events.<ref name="Lew2018" /> No increased risk of suicide or depression was conclusively found.<ref name="Lew2018" /> Medical authorities strictly regulate isotretinoin use in women of childbearing age due to its known [[teratogenicity|harmful effects in pregnancy]].<ref name="BMJ2013" /> For such a woman to be considered a candidate for isotretinoin, she must have a confirmed negative [[pregnancy test]] and use an effective form of [[contraception|birth control]].<ref name="BMJ2013" /> In 2008, the United States started the [[iPLEDGE]] program to prevent isotretinoin use during pregnancy.<ref name="Tan2016" /> iPLEDGE requires the woman to have two negative pregnancy tests and to use two types of birth control for at least one month before isotretinoin therapy begins and one month afterward.<ref name="Tan2016" /> The effectiveness of the iPLEDGE program is controversial due to continued instances of contraception nonadherence.<ref name="Tan2016">{{cite journal | vauthors = Tan J, Boyal S, Desai K, Knezevic S | title = Oral Isotretinoin: New Developments Relevant to Clinical Practice | journal = Dermatologic Clinics | volume = 34 | issue = 2 | pages = 175–84 | date = April 2016 | pmid = 27015777 | doi = 10.1016/j.det.2015.11.002 | type = Review }}</ref><ref name="Pre2013">{{cite journal | vauthors = Prevost N, English JC | title = Isotretinoin: update on controversial issues | journal = Journal of Pediatric and Adolescent Gynecology | volume = 26 | issue = 5 | pages = 290–3 | date = October 2013 | pmid = 24147278 | doi = 10.1016/j.jpag.2013.05.007 | type = Review }}</ref> ====Antibiotics==== People may apply antibiotics to the skin or take them orally to treat acne. They work by killing ''C. acnes'' and reducing inflammation.<ref name=BMJ2013/><ref name=Benz09/><ref name="Walsh2016">{{cite journal | vauthors = Walsh TR, Efthimiou J, Dréno B | title = Systematic review of antibiotic resistance in acne: an increasing topical and oral threat | journal = The Lancet. Infectious Diseases | volume = 16 | issue = 3 | pages = e23-33 | date = March 2016 | pmid = 26852728 | doi = 10.1016/S1473-3099(15)00527-7 | s2cid = 206154465 | url = http://orca.cf.ac.uk/102767/1/acne.pdf | type = Systematic Review | access-date = 1 January 2019 | archive-url = https://web.archive.org/web/20181105012154/http://orca.cf.ac.uk/102767/1/acne.pdf | archive-date = 5 November 2018 | url-status = live }}</ref> Although multiple guidelines call for healthcare providers to reduce the rates of prescribed oral antibiotics, many providers do not follow this guidance.<ref name="Barbieri2019">{{cite journal | vauthors = Barbieri JS, Spaccarelli N, Margolis DJ, James WD | title = Approaches to limit systemic antibiotic use in acne: Systemic alternatives, emerging topical therapies, dietary modification, and laser and light-based treatments | journal = Journal of the American Academy of Dermatology | volume = 80 | issue = 2 | pages = 538–549 | date = February 2019 | pmid = 30296534 | pmc = 6333507 | doi = 10.1016/j.jaad.2018.09.055 | type = Review }}</ref> Oral antibiotics remain the most commonly prescribed systemic therapy for acne.<ref name="Barbieri2019"/> Widespread [[broad-spectrum antibiotic]] overuse for acne has led to higher rates of antibiotic-resistant ''C. acnes'' strains worldwide, especially to the commonly used [[tetracycline]] (e.g., [[doxycycline]]) and macrolide antibiotics (e.g., topical [[erythromycin]]).<ref name="ReferenceA"/><ref name=Benz09/><ref name="Walsh2016"/><ref name="Barbieri2019"/> Therefore, dermatologists prefer antibiotics as part of combination therapy and not for use alone.<ref name="Zaenglein2018"/> Commonly used antibiotics, either applied to the skin or taken orally, include [[clindamycin]], erythromycin, [[metronidazole]], [[sulfacetamide]], and tetracyclines (e.g., doxycycline or [[minocycline]]).<ref name=Kong2013/> Doxycycline 40 milligrams daily (low-dose) appears to have similar efficacy to 100 milligrams daily and has fewer gastrointestinal side effects.<ref name="Zaenglein2018" /> However, low-dose doxycycline is not FDA-approved for the treatment of acne.<ref>{{cite web|last=Hilton|first=Lisette|date=2019-03-21|title=Dermatologists relying less on antibiotics for acne|url=https://www.dermatologytimes.com/article/dermatologists-relying-less-antibiotics-acne|access-date=2020-06-07|website=Dermatology Times|archive-date=7 June 2020|archive-url=https://web.archive.org/web/20200607011250/https://www.dermatologytimes.com/article/dermatologists-relying-less-antibiotics-acne|url-status=dead}}</ref> Antibiotics applied to the skin are typically used for mild to moderately severe acne.<ref name=BMJ2013/> Oral antibiotics are generally more effective than topical antibiotics and produce faster resolution of inflammatory acne lesions than topical applications.<ref name=Vary2015/> The ''Global Alliance to Improve Outcomes in Acne'' recommends that topical and oral antibiotics are not used together.<ref name="Walsh2016" /> Oral antibiotics are recommended for no longer than three months as antibiotic courses exceeding this duration are associated with the development of antibiotic resistance and show no clear benefit over shorter durations.<ref name="Walsh2016" /> If long-term oral antibiotics beyond three months are used, then it is recommended that benzoyl peroxide or a retinoid be used at the same time to limit the risk of ''C. acnes'' developing antibiotic resistance.<ref name="Walsh2016" /> The antibiotic [[dapsone]] is effective against inflammatory acne when applied to the skin. It is generally not a first-line choice due to its higher cost and a lack of clear superiority over other antibiotics.<ref name=Vary2015/><ref name="Zaenglein2018" /> Topical dapsone is sometimes a preferred therapy in women or for people with sensitive or darker-toned skin.<ref name="Zaenglein2018"/> It is not recommended for use with benzoyl peroxide due to the risk of causing yellow-orange skin discoloration with this combination.<ref name="Aslam2015"/> Minocycline is an effective acne treatment, but it is not a first-line antibiotic due to a lack of evidence that it is better than other treatments, and concerns about its safety compared to other tetracyclines.<ref>{{cite journal | vauthors = Garner SE, Eady A, Bennett C, Newton JN, Thomas K, Popescu CM | title = Minocycline for acne vulgaris: efficacy and safety | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD002086 | date = August 2012 | volume = 2012 | pmid = 22895927 | doi = 10.1002/14651858.CD002086.pub2 | pmc = 7017847 }}</ref> [[Sarecycline]] is the most recent oral antibiotic developed specifically for the treatment of acne, and is FDA-approved for the treatment of moderate to severe inflammatory acne in patients nine years of age and older.<ref>{{cite web|title=Prescribing Information for Seysara|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209521s007lbl.pdf|access-date=7 June 2020|archive-date=7 June 2020|archive-url=https://web.archive.org/web/20200607011241/https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209521s007lbl.pdf|url-status=live}}</ref><ref>{{cite journal | vauthors = Leyden JJ, Sniukiene V, Berk DR, Kaoukhov A | title = Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study | journal = Journal of Drugs in Dermatology | volume = 17 | issue = 3 | pages = 333–338 | date = March 2018 | pmid = 29537451 | url = http://jddonline.com/articles/dermatology/S1545961618P0333X | access-date = 24 July 2021 | archive-date = 3 August 2021 | archive-url = https://web.archive.org/web/20210803211526/https://jddonline.com/articles/dermatology/S1545961618P0333X | url-status = live }}</ref><ref name=":1">{{cite journal | vauthors = Moore AY, Charles JE, Moore S | title = Sarecycline: a narrow spectrum tetracycline for the treatment of moderate-to-severe acne vulgaris | journal = Future Microbiology | volume = 14 | pages = 1235–1242 | date = September 2019 | issue = 14 | pmid = 31475868 | pmc = 6802708 | doi = 10.2217/fmb-2019-0199 }}</ref> It is a [[Narrow-spectrum antibiotic|narrow-spectrum]] tetracycline antibiotic that exhibits the necessary antibacterial activity against pathogens related to acne vulgaris and a low propensity for inducing antibiotic resistance.<ref>{{cite journal |journal=PubChem |title=Sarecycline |url=https://pubchem.ncbi.nlm.nih.gov/compound/54681908 |access-date=2020-06-07 |publisher=U.S. National Library of Medicine |archive-date=24 July 2020 |archive-url=https://web.archive.org/web/20200724225741/https://pubchem.ncbi.nlm.nih.gov/compound/54681908 |url-status=live }}</ref><ref>{{cite journal | vauthors = Zhanel G, Critchley I, Lin LY, Alvandi N | title = Microbiological Profile of Sarecycline, a Novel Targeted Spectrum Tetracycline for the Treatment of Acne Vulgaris | journal = Antimicrobial Agents and Chemotherapy | volume = 63 | issue = 1 | date = January 2019 | pmid = 30397052 | pmc = 6325184 | doi = 10.1128/AAC.01297-18 }}</ref> In clinical trials, sarecycline demonstrated clinical efficacy in reducing inflammatory acne lesions as early as three weeks and reduced truncal (back and chest) acne.<ref name=":1" /><ref>{{cite journal | vauthors = Moore A, Green LJ, Bruce S, Sadick N, Tschen E, Werschler P, Cook-Bolden FE, Dhawan SS, Forsha D, Gold MH, Guenthner S, Kempers SE, Kircik LH, Parish JL, Rendon MI, Rich P, Stein-Gold L, Tyring SK, Weiss RA, Nasir A, Schmitz C, Boodhoo TI, Kaoukhov A, Berk DR | display-authors = 6 | title = Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials | journal = Journal of Drugs in Dermatology | volume = 17 | issue = 9 | pages = 987–996 | date = September 2018 | pmid = 30235387 | url = http://jddonline.com/articles/dermatology/S1545961618P0987X | access-date = 24 July 2021 | archive-date = 24 July 2021 | archive-url = https://web.archive.org/web/20210724033025/https://jddonline.com/articles/dermatology/S1545961618P0987X | url-status = live }}</ref> ====Hormonal agents==== In women, the use of [[combined birth control pill]]s can improve acne.<ref name=Tyler2013>{{cite journal | vauthors = Arowojolu AO, Gallo MF, Lopez LM, Grimes DA | veditors = Arowojolu AO | title = Combined oral contraceptive pills for treatment of acne | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 7 | pages = CD004425 | date = July 2012 | pmid = 22786490 | doi = 10.1002/14651858.CD004425.pub6 | type = Systematic Review & Meta-Analysis | pmc = 11437354 }}</ref> These medications contain an [[estrogen (medication)|estrogen]] and a [[progestin]].<ref name="Kuhl1999" /> They work by decreasing the production of androgen hormones by the ovaries and by decreasing the free and hence biologically active fractions of androgens, resulting in lowered skin production of sebum and consequently reduce acne severity.<ref name="Aslam2015"/><ref name="pmid22994662">{{cite journal | vauthors = Kamangar F, Shinkai K | title = Acne in the adult female patient: a practical approach | journal = International Journal of Dermatology | volume = 51 | issue = 10 | pages = 1162–74 | date = October 2012 | pmid = 22994662 | doi = 10.1111/j.1365-4632.2012.05519.x | s2cid = 5777817 | doi-access = free }}</ref> First-generation progestins such as [[norethindrone]] and [[norgestrel]] have androgenic properties and may worsen acne.<ref name="Zaenglein2018"/> Although oral estrogens decrease IGF-1 levels in some situations, which could theoretically improve acne symptoms,<ref name="pmid16112947">{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | pages = 3–63 | date = August 2005 | issue = Suppl 1 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf | access-date = 21 December 2018 | archive-url = https://web.archive.org/web/20160822055012/http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf | archive-date = 22 August 2016 | url-status = live }}</ref><ref name="pmid27704479">{{cite journal | vauthors = Duarte FH, Jallad RS, Bronstein MD | title = Estrogens and selective estrogen receptor modulators in acromegaly | journal = Endocrine | volume = 54 | issue = 2 | pages = 306–314 | date = November 2016 | pmid = 27704479 | doi = 10.1007/s12020-016-1118-z | s2cid = 10136018 }}</ref> combined birth control pills do not appear to affect IGF-1 levels in fertile women.<ref name="Kuhl1999">{{cite book |doi=10.1007/978-3-642-60107-1_18 |chapter=Hormonal Contraception |title=Estrogens and Antiestrogens II |series=Handbook of Experimental Pharmacology |year=1999 |last1=Kuhl |first1=H. |volume=135 / 2 |pages=363–407 |isbn=978-3-642-64261-6 }}</ref><ref name="Kuhl1997">{{cite journal |last1=Kuhl |first1=H. |title=Metabolische Effekte der Östrogene und Gestagene |journal=Der Gynäkologe |date=18 April 1997 |volume=30 |issue=4 |pages=357–369 |doi=10.1007/PL00003042 |s2cid=43381309 }}</ref> [[Cyproterone acetate]]-containing birth control pills seem to decrease total and free IGF-1 levels.<ref name="pmid15832490">{{cite journal | vauthors = Wiegratz I, Kuhl H | title = Managing cutaneous manifestations of hyperandrogenic disorders: the role of oral contraceptives | journal = Treatments in Endocrinology | volume = 1 | issue = 6 | pages = 372–86 | date = 2002 | pmid = 15832490 | doi = 10.2165/00024677-200201060-00003 | s2cid = 71806394 }}</ref> Combinations containing third- or fourth-generation [[progestin]]s, including [[desogestrel]], [[dienogest]], [[drospirenone]], or [[norgestimate]], as well as birth control pills containing cyproterone acetate or [[chlormadinone acetate]], are preferred for women with acne due to their stronger antiandrogenic effects.<ref name="pmid22786490">{{cite journal | vauthors = Arowojolu AO, Gallo MF, Lopez LM, Grimes DA | veditors = Arowojolu AO | title = Combined oral contraceptive pills for treatment of acne | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD004425 | date = July 2012 | pmid = 22786490 | doi = 10.1002/14651858.CD004425.pub6 | pmc = 11437354 }}</ref><ref name="Powell2017">{{cite journal | vauthors = Powell A | title = Choosing the Right Oral Contraceptive Pill for Teens | journal = Pediatric Clinics of North America | volume = 64 | issue = 2 | pages = 343–358 | date = April 2017 | pmid = 28292450 | doi = 10.1016/j.pcl.2016.11.005 | type = Review }}</ref><ref name="pmid29725277">{{cite journal | vauthors = Słopień R, Milewska E, Rynio P, Męczekalski B | title = Use of oral contraceptives for management of acne vulgaris and hirsutism in women of reproductive and late reproductive age | journal = Przeglad Menopauzalny = Menopause Review | volume = 17 | issue = 1 | pages = 1–4 | date = March 2018 | pmid = 29725277 | pmc = 5925193 | doi = 10.5114/pm.2018.74895 }}</ref> Studies have shown a 40 to 70% reduction in acne lesions with combined birth control pills.<ref name="pmid22994662" /> A 2014 [[systematic review|review]] found that oral antibiotics appear to be somewhat more effective than birth control pills at reducing the number of inflammatory acne lesions at three months.<ref name=Koo2014>{{cite journal | vauthors = Koo EB, Petersen TD, Kimball AB | title = Meta-analysis comparing efficacy of antibiotics versus oral contraceptives in acne vulgaris | journal = Journal of the American Academy of Dermatology | volume = 71 | issue = 3 | pages = 450–9 | date = September 2014 | pmid = 24880665 | doi = 10.1016/j.jaad.2014.03.051 | type = Systematic Review & Meta-Analysis }}</ref> However, the two therapies are approximately equal in efficacy at six months for decreasing the number of inflammatory, non-inflammatory, and total acne lesions.<ref name=Koo2014/> The authors of the analysis suggested that birth control pills may be a preferred first-line acne treatment, over oral antibiotics, in certain women due to similar efficacy at six months and a lack of associated antibiotic resistance.<ref name=Koo2014/> In contrast to combined birth control pills, [[progestogen-only birth control]] forms that contain androgenic progestins have been associated with worsened acne.<ref name="Barbieri2019"/> [[Antiandrogen]]s such as cyproterone acetate and [[spironolactone]] can successfully treat acne, especially in women with signs of excessive androgen production, such as increased [[hirsutism|hairiness]] or skin production of sebum, or [[alopecia|scalp hair loss]].<ref name="Aslam2015"/><ref name=Kong2013/> Spironolactone is an effective treatment for acne in adult women.<ref name="pmid28155090" /><ref>{{cite journal |last1=Santer |first1=Miriam |last2=Lawrence |first2=Megan |last3=Renz |first3=Susanne |last4=Eminton |first4=Zina |last5=Stuart |first5=Beth |last6=Sach |first6=Tracey H |last7=Pyne |first7=Sarah |last8=Ridd |first8=Matthew J |last9=Francis |first9=Nick |last10=Soulsby |first10=Irene |last11=Thomas |first11=Karen |last12=Permyakova |first12=Natalia |last13=Little |first13=Paul |last14=Muller |first14=Ingrid |last15=Nuttall |first15=Jacqui |date=2023-05-16 |title=Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial |journal=The BMJ |volume=381|pages=e074349 |doi=10.1136/bmj-2022-074349 |pmid=37192767 |pmc=10543374 |s2cid=258717921 |issn=1756-1833|doi-access=free }}</ref> Unlike combined birth control pills, it is not approved by the United States [[Food and Drug Administration]] for this purpose.<ref name=Vary2015/><ref name=Yin2014/><ref name="pmid28155090">{{cite journal | vauthors = Layton AM, Eady EA, Whitehouse H, Del Rosso JQ, Fedorowicz Z, van Zuuren EJ | title = Oral Spironolactone for Acne Vulgaris in Adult Females: A Hybrid Systematic Review | journal = American Journal of Clinical Dermatology | volume = 18 | issue = 2 | pages = 169–191 | date = April 2017 | pmid = 28155090 | pmc = 5360829 | doi = 10.1007/s40257-016-0245-x }}</ref> Spironolactone is an [[aldosterone antagonist]] and is a useful acne treatment due to its ability to additionally block the [[androgen receptor]] at higher doses.<ref name=Yin2014/><ref name="Barbieri2019"/> Alone or in combination with a birth control pill, spironolactone has shown a 33 to 85% reduction in acne lesions in women.<ref name="pmid22994662" /> The effectiveness of spironolactone for acne appears to be dose-dependent.<ref name="pmid22994662" /> High-dose cyproterone acetate alone reportedly decreases acne symptoms in women by 75 to 90% within three months.<ref name="pmid25627824" /> It is usually combined with an estrogen to avoid [[menstrual irregularities]] and [[estrogen deficiency]].<ref name="pmid9856417">{{cite journal | vauthors = Diamanti-Kandarakis E | title = How actual is the treatment with antiandrogen alone in patients with polycystic ovary syndrome? | journal = Journal of Endocrinological Investigation | volume = 21 | issue = 9 | pages = 623–9 | date = October 1998 | pmid = 9856417 | doi = 10.1007/BF03350788 | s2cid = 46484837 }}</ref> The medication appears to be effective in the treatment of acne in males, with one study finding that a high dosage reduced inflammatory acne lesions by 73%.<ref name="WardBrogden1984">{{cite journal | vauthors = Ward A, Brogden RN, Heel RC, Speight TM, Avery GS | title = Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders | journal = Drugs | volume = 28 | issue = 1 | pages = 6–37 | date = July 1984 | pmid = 6235105 | doi = 10.2165/00003495-198428010-00002 }}</ref><ref name="Rasmusson1986">{{cite book |doi=10.1016/S0065-7743(08)61128-8 |title=Chapter 18. Chemical Control of Androgen Action |series=Annual Reports in Medicinal Chemistry |year=1986 |last1=Rasmusson |first1=Gary H. |volume=21 |pages=179–188 |isbn=9780120405213 }}</ref> However, spironolactone and cyproterone acetate's side effects in males, such as [[gynecomastia]], [[sexual dysfunction]], and decreased [[bone mineral density]], generally make their use for male acne impractical.<ref name="WardBrogden1984" /><ref name="Rasmusson1986" /><ref name="pmid19297634">{{cite journal | vauthors = Giltay EJ, Gooren LJ | title = Potential side effects of androgen deprivation treatment in sex offenders | journal = The Journal of the American Academy of Psychiatry and the Law | volume = 37 | issue = 1 | pages = 53–8 | date = 2009 | pmid = 19297634 }}</ref> Pregnant and lactating women should not receive antiandrogens for their acne due to a possibility of [[congenital disorder|birth disorders]] such as [[hypospadias]] and [[Feminization (biology)|feminization]] of male babies.<ref name=Kong2013/> Women who are sexually active and who can or may become pregnant should use an effective method of contraception to prevent pregnancy while taking an antiandrogen.<ref name="pmid30312645" /> Antiandrogens are often combined with birth control pills for this reason, which can result in additive efficacy.<ref name=Yin2014 /><ref name="pmid25896771">{{cite journal | vauthors = Oudenhoven MD, Kinney MA, McShane DB, Burkhart CN, Morrell DS | title = Adverse effects of acne medications: recognition and management | journal = American Journal of Clinical Dermatology | volume = 16 | issue = 4 | pages = 231–242 | date = August 2015 | pmid = 25896771 | doi = 10.1007/s40257-015-0127-7 | s2cid = 37512606 }}</ref> The FDA added a [[Boxed warning|black-box warning]] to spironolactone about possible [[tumor]] risks based on [[preclinical research]] with very high doses (>100-fold clinical doses) and cautioned that unnecessary use of the medication should be avoided.<ref name="Zaenglein2016"/><ref name="Barbieri2019" /><ref>{{cite web|title=FDA. Prescribing Information|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/012151s062lbl.pdf|access-date=7 June 2020|archive-date=24 August 2020|archive-url=https://web.archive.org/web/20200824235422/https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/012151s062lbl.pdf|url-status=live}}</ref> However, several large [[epidemiological study|epidemiological studies]] subsequently found no greater risk of tumors in association with spironolactone in humans.<ref name="Barbieri2019" /><ref name="pmid30467659">{{cite journal | vauthors = Rozner RN, Freites-Martinez A, Shapiro J, Geer EB, Goldfarb S, Lacouture ME | title = Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies | journal = Breast Cancer Res. Treat. | volume = 174 | issue = 1 | pages = 15–26 | date = February 2019 | pmid = 30467659 | pmc = 6773272 | doi = 10.1007/s10549-018-4996-3 }}</ref><ref name="pmid28979664">{{cite journal | vauthors = Endly DC, Miller RA | title = Oily Skin: A review of Treatment Options | journal = J Clin Aesthet Dermatol | volume = 10 | issue = 8 | pages = 49–55 | date = August 2017 | pmid = 28979664 | pmc = 5605215 }}</ref><ref name="pmid32738426">{{cite journal | vauthors = Heymann WR | title = Spironolactone and breast cancer: Fear not! | journal = J. Am. Acad. Dermatol. | date = July 2020 | volume = 83 | issue = 4 | pages = 1008–1009 | pmid = 32738426 | doi = 10.1016/j.jaad.2020.07.104 | s2cid = 220924754 }}</ref> Conversely, strong associations of cyproterone acetate with certain [[brain tumor]]s have been discovered and its use has been restricted.<ref name="SenofontePallotti2020">{{cite journal |last1=Senofonte |first1=Giulia |last2=Pallotti |first2=Francesco |last3=Lombardo |first3=Francesco |title=Ciproterone acetato e meningiomi: lo stato dell'arte |trans-title=Cyproterone acetate and meningiomas: the state of the art |language=it |journal=L'Endocrinologo |date=June 2020 |volume=21 |issue=3 |pages=171–175 |doi=10.1007/s40619-020-00746-8 |doi-access=free |hdl=11573/1492686 |hdl-access=free }}</ref><ref name="pmid32419942">{{cite journal | vauthors = Kohl S | title = Council of Europe resolution to promote pharmaceutical care in Europe | journal = Eur J Hosp Pharm | volume = 27 | issue = 3 | pages = 184–188 | date = May 2020 | pmid = 32419942 | doi = 10.1136/ejhpharm-2020-002305 | pmc = 7223358 }}</ref><ref name="pmid33536184">{{cite journal | vauthors = Weill A, Nguyen P, Labidi M, Cadier B, Passeri T, Duranteau L, Bernat AL, Yoldjian I, Fontanel S, Froelich S, Coste J | title = Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study | journal = The BMJ | volume = 372 | pages = n37 | date = February 2021 | pmid = 33536184 | doi = 10.1136/bmj.n37 | doi-access = free }}</ref> The brain tumor risk with cyproterone acetate is due to its strong [[progestogen (medication)|progestogenic]] actions and is not related to antiandrogenic activity nor shared by other antiandrogens.<ref name="SenofontePallotti2020" /><ref name="pmid32705456">{{cite journal | vauthors = Apra C, Roblot P, Alkhayri A, Le Guérinel C, Polivka M, Chauvet D | title = Female gender and exogenous progesterone exposition as risk factors for spheno-orbital meningiomas | journal = J. Neurooncol. | date = July 2020 | volume = 149 | issue = 1 | pages = 95–101 | pmid = 32705456 | doi = 10.1007/s11060-020-03576-8 | s2cid = 220720801 | url = https://hal.sorbonne-universite.fr/hal-03270880/file/Apra%20et%20al.%20-%202020%20-%20Female%20gender%20and%20exogenous%20progesterone%20expositio.pdf | access-date = 18 August 2021 | archive-date = 4 September 2021 | archive-url = https://web.archive.org/web/20210904051802/https://hal.sorbonne-universite.fr/hal-03270880/file/Apra%20et%20al.%20-%202020%20-%20Female%20gender%20and%20exogenous%20progesterone%20expositio.pdf | url-status = live }}</ref><ref name="pmid33536184" /> [[Flutamide]], a pure [[receptor antagonist|antagonist]] of the androgen receptor, is effective in treating acne in women.<ref name="pmid25627824">{{cite journal | vauthors = Bettoli V, Zauli S, Virgili A | title = Is hormonal treatment still an option in acne today? | journal = The British Journal of Dermatology | volume = 172 | pages = 37–46 | date = July 2015 | issue = Suppl 1 | pmid = 25627824 | doi = 10.1111/bjd.13681 | s2cid = 35615492 | doi-access = }}</ref><ref name="pmid25845307">{{cite journal | vauthors = Husein-ElAhmed H | title = Management of acne vulgaris with hormonal therapies in adult female patients | journal = Dermatologic Therapy | volume = 28 | issue = 3 | pages = 166–72 | year = 2015 | pmid = 25845307 | doi = 10.1111/dth.12231 | s2cid = 2628354 | doi-access = free }}</ref> It appears to reduce acne symptoms by 80 to 90% even at low doses, with several studies showing complete acne clearance.<ref name="pmid25627824" /><ref name="pmid28562419">{{cite journal | vauthors = Nguyen HL, Tollefson MM | title = Endocrine disorders and hormonal therapy for adolescent acne | journal = Current Opinion in Pediatrics | volume = 29 | issue = 4 | pages = 455–465 | date = August 2017 | pmid = 28562419 | doi = 10.1097/MOP.0000000000000515 | s2cid = 4640778 }}</ref><ref name="pmid10495361">{{cite journal | vauthors = Diamanti-Kandarakis E | title = Current aspects of antiandrogen therapy in women | journal = Current Pharmaceutical Design | volume = 5 | issue = 9 | pages = 707–23 | date = September 1999 | doi = 10.2174/1381612805666230111201150 | pmid = 10495361 | url = https://books.google.com/books?id=9rfNZL6oEO0C&pg=PA707 | access-date = 21 December 2018 | archive-url = https://web.archive.org/web/20200227012541/https://books.google.com/books?id=9rfNZL6oEO0C&pg=PA707 | archive-date = 27 February 2020 | url-status = live }}</ref> In one study, flutamide decreased acne scores by 80% within three months, whereas spironolactone decreased symptoms by only 40% in the same period.<ref name="pmid10495361" /><ref name="ShelleyShelley2001">{{cite book|first1=Walter Brown|last1=Shelley|first2=E. Dorinda|last2=Shelley|title=Advanced Dermatologic Therapy II|url=https://books.google.com/books?id=vuJsAAAAMAAJ|year=2001|publisher=W. B. Saunders|isbn=978-0-7216-8258-7|access-date=21 December 2018|archive-date=11 January 2023|archive-url=https://web.archive.org/web/20230111121854/https://books.google.com/books?id=vuJsAAAAMAAJ|url-status=live}}</ref><ref name="BalenFranks2010">{{cite book | first1 = Adam | last1 = Balen | first2 = Stephen | last2 = Franks | first3 = Roy | last3 = Homburg | first4 = Sean | last4 = Kehoe | title = Current Management of Polycystic Ovary Syndrome | url = https://books.google.com/books?id=0rtUBAAAQBAJ&pg=PA132 | date = October 2010 | publisher = Cambridge University Press | isbn = 978-1-906985-41-7 | pages = 132– | access-date = 21 December 2018 | archive-date = 11 January 2023 | archive-url = https://web.archive.org/web/20230111121859/https://books.google.com/books?id=0rtUBAAAQBAJ&pg=PA132 | url-status = live }}</ref> In a large long-term study, 97% of women reported satisfaction with the control of their acne with flutamide.<ref name="pmid28492054">{{cite journal | vauthors = Trivedi MK, Shinkai K, Murase JE | title = A Review of hormone-based therapies to treat adult acne vulgaris in women | journal = International Journal of Women's Dermatology | volume = 3 | issue = 1 | pages = 44–52 | date = March 2017 | pmid = 28492054 | pmc = 5419026 | doi = 10.1016/j.ijwd.2017.02.018 }}</ref> Although effective, flutamide has a risk of serious [[liver toxicity]], and cases of death in women taking even low doses of the medication to treat androgen-dependent skin and hair conditions have occurred.<ref name="pmid28379593">{{cite journal | vauthors = Giorgetti R, di Muzio M, Giorgetti A, Girolami D, Borgia L, Tagliabracci A | title = Flutamide-induced hepatotoxicity: ethical and scientific issues | journal = European Review for Medical and Pharmacological Sciences | volume = 21 | issue = 1 Suppl | pages = 69–77 | date = March 2017 | pmid = 28379593 }}</ref> As such, the use of flutamide for acne has become increasingly limited,<ref name="pmid28492054" /><ref name="YasaDural2016">{{cite journal |last1=Yasa |first1=Cenk |last2=Dural |first2=Özlem |last3=Bastu |first3=Ercan |last4=Uğurlucan |first4=Funda Güngör |title=Hirsutism, Acne, and Hair Loss: Management of Hyperandrogenic Cutaneous Manifestations of Polycystic Ovary Syndrome |journal=Gynecology Obstetrics & Reproductive Medicine |date=22 August 2017 |volume=23 |issue=2 |pages=110–119 |doi=10.21613/GORM.2016.613 |doi-access=free }}</ref><ref name="pmid28274354">{{cite journal | vauthors = Barros B, Thiboutot D | title = Hormonal therapies for acne | journal = Clinics in Dermatology | volume = 35 | issue = 2 | pages = 168–172 | date = 2017 | pmid = 28274354 | doi = 10.1016/j.clindermatol.2016.10.009 }}</ref> and it has been argued that continued use of flutamide for such purposes is unethical.<ref name="pmid28379593" /> [[Bicalutamide]], a pure androgen receptor antagonist with the same mechanism as flutamide and with comparable or superior antiandrogenic [[efficacy]] but with a far lower risk of liver toxicity, is an alternative option to flutamide in the treatment of androgen-dependent skin and hair conditions in women.<ref name="pmid30312645">{{cite journal | vauthors = Azarchi S, Bienenfeld A, Lo Sicco K, Marchbein S, Shapiro J, Nagler AR | title = Androgens in women: Hormone-modulating therapies for skin disease | journal = Journal of the American Academy of Dermatology | volume = 80 | issue = 6 | pages = 1509–1521 | date = June 2019 | pmid = 30312645 | doi = 10.1016/j.jaad.2018.08.061 | s2cid = 52973096 }}</ref><ref name="pmid8717470">{{cite journal | vauthors = Blackledge GR | title = Clinical progress with a new antiandrogen, Casodex (bicalutamide) | journal = European Urology | volume = 29 Suppl 2 | issue = 2 | pages = 96–104 | date = 1996 | pmid = 8717470 | doi = 10.1159/000473847 }}</ref><ref name="pmid14748655">{{cite journal | vauthors = Fradet Y | title = Bicalutamide (Casodex) in the treatment of prostate cancer | journal = Expert Review of Anticancer Therapy | volume = 4 | issue = 1 | pages = 37–48 | date = February 2004 | pmid = 14748655 | doi = 10.1586/14737140.4.1.37 | s2cid = 34153031 }}</ref><ref name="pmid27416311">{{cite journal | vauthors = Hassoun LA, Chahal DS, Sivamani RK, Larsen LN | title = The use of hormonal agents in the treatment of acne | journal = Seminars in Cutaneous Medicine and Surgery | volume = 35 | issue = 2 | pages = 68–73 | date = June 2016 | pmid = 27416311 | doi = 10.12788/j.sder.2016.027 | doi-broken-date = 21 December 2024 }}</ref> [[Clascoterone]] is a [[topical administration|topical]] antiandrogen that has demonstrated effectiveness in the treatment of acne in both males and females and was approved for clinical use for this indication in August 2020.<ref name="Winlevi FDA label">{{cite web | url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213433s000lbl.pdf | title=Winlevi (clascoterone) cream, for topical use | publisher=Cassiopea | access-date=9 September 2020 | archive-date=18 September 2020 | archive-url=https://web.archive.org/web/20200918114726/https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213433s000lbl.pdf | url-status=live }}</ref><ref name="pmid30466681">{{cite journal | vauthors = Marson JW, Baldwin HE | title = New Concepts, Concerns, and Creations in Acne | journal = Dermatologic Clinics | volume = 37 | issue = 1 | pages = 1–9 | date = January 2019 | pmid = 30466681 | doi = 10.1016/j.det.2018.07.002 | s2cid = 53718051 | type = Review }}</ref><ref name="Timmins2018">{{cite journal | title = Industry update: the latest developments in the field of therapeutic delivery, July 2018 | journal = Therapeutic Delivery | volume = 9 | issue = 11 | pages = 797–809 | year = 2018 | doi = 10.4155/tde-2018-0055 | type = Review | last1 = Timmins | first1 = Peter| doi-access = free }}</ref><ref name="pmid29594974">{{cite journal | vauthors = Trivedi MK, Bosanac SS, Sivamani RK, Larsen LN | title = Emerging Therapies for Acne Vulgaris | journal = American Journal of Clinical Dermatology | volume = 19 | issue = 4 | pages = 505–516 | date = August 2018 | pmid = 29594974 | doi = 10.1007/s40257-018-0345-x | s2cid = 4398912 | type = Review }}</ref><ref name="pmid29872679">{{cite journal | vauthors = Tan AU, Schlosser BJ, Paller AS | title = A review of diagnosis and treatment of acne in adult female patients | journal = International Journal of Women's Dermatology | volume = 4 | issue = 2 | pages = 56–71 | date = June 2018 | pmid = 29872679 | pmc = 5986265 | doi = 10.1016/j.ijwd.2017.10.006 | type = Review }}</ref> It has shown no systemic absorption or associated antiandrogenic side effects.<ref name="pmid29594974" /><ref name="pmid29872679" /><ref name="pmid25474485">{{cite journal | vauthors = Aslam I, Fleischer A, Feldman S | title = Emerging drugs for the treatment of acne | journal = Expert Opinion on Emerging Drugs | volume = 20 | issue = 1 | pages = 91–101 | date = March 2015 | pmid = 25474485 | doi = 10.1517/14728214.2015.990373 | s2cid = 12685388 }}</ref> In a small direct head-to-head comparison, clascoterone showed greater effectiveness than topical isotretinoin.<ref name="pmid29594974" /><ref name="pmid29872679" /><ref name="pmid25474485" /> [[5α-Reductase inhibitor]]s such as [[finasteride]] and [[dutasteride]] may be useful for the treatment of acne in both males and females but have not been adequately evaluated for this purpose.<ref name=Vary2015/><ref name="pmid23377402">{{cite journal | vauthors = Azzouni F, Zeitouni N, Mohler J | url = https://jddonline.com/articles/dermatology/S1545961613E0030X | title = Role of 5α-reductase inhibitors in androgen-stimulated skin disorders | journal = Journal of Drugs in Dermatology | volume = 12 | issue = 2 | pages = e30-5 | date = February 2013 | pmid = 23377402 | access-date = 31 August 2020 | archive-date = 9 August 2020 | archive-url = https://web.archive.org/web/20200809085939/https://jddonline.com/articles/dermatology/S1545961613E0030X | url-status = live }}</ref><ref name="Danby2015">{{cite book|first=F. William|last=Danby|title=Acne: Causes and Practical Management|url=https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA147|date=27 January 2015|publisher=John Wiley & Sons|isbn=978-1-118-23277-4|pages=147–|access-date=21 December 2018|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031704/https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA147|url-status=live}}</ref><ref name="pmid23431485">{{cite journal | vauthors = Marchetti PM, Barth JH | title = Clinical biochemistry of dihydrotestosterone | journal = Annals of Clinical Biochemistry | volume = 50 | issue = Pt 2 | pages = 95–107 | date = March 2013 | pmid = 23431485 | doi = 10.1258/acb.2012.012159 | s2cid = 8325257 | doi-access = free }}</ref> Moreover, 5α-reductase inhibitors have a strong potential for producing birth defects in male babies and this limits their use in women.<ref name=Vary2015/><ref name="Danby2015" /> However, 5α-reductase inhibitors are frequently used to treat [[hirsutism|excessive facial/body hair]] in women and can be combined with birth control pills to prevent pregnancy.<ref name="pmid23377402" /> There is no evidence as of 2010 to support the use of [[cimetidine]] or [[ketoconazole]] in the treatment of acne.<ref name="pmid20082945">{{cite journal | vauthors = Katsambas AD, Dessinioti C | title = Hormonal therapy for acne: why not as first line therapy? facts and controversies | journal = Clinics in Dermatology | volume = 28 | issue = 1 | pages = 17–23 | date = 2010 | pmid = 20082945 | doi = 10.1016/j.clindermatol.2009.03.006 }}</ref> Hormonal treatments for acne such as combined birth control pills and antiandrogens may be considered first-line therapy for acne under many circumstances, including desired contraception, known or suspected hyperandrogenism, acne during adulthood, acne that flares premenstrually, and when symptoms of significant sebum production (seborrhea) are co-present.<ref name="pmid20082945" /> Hormone therapy is effective for acne both in women with hyperandrogenism and in women with normal androgen levels.<ref name="pmid20082945" /> ====Azelaic acid==== {{Self-contradictory|section|about=efficacy|date=December 2023}} [[Azelaic acid]] is effective for mild to moderate acne when applied topically at a 15–20% concentration.<ref name=Sieber2014/><ref name=Pugashetti2013/><ref>{{cite journal |last1=Gollnick |first1=Harald P. M. |last2=Graupe |first2=Klaus |last3=Zaumseil |first3=Rolf-Peter |title=15% Azelainsauregel in der Behandlung der Akne. Zwei doppelblinde klinische Vergleichsstudien. [[Azelaic acid]] 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies |journal=Journal der Deutschen Dermatologischen Gesellschaft |date=October 2004 |volume=2 |issue=10 |pages=841–847 |doi=10.1046/j.1439-0353.2004.04731.x |pmid=16281587 |s2cid=58809558 }}</ref><ref>{{cite journal |last1=Thiboutot |first1=D |title=Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris |journal=Journal of Drugs in Dermatology |date=January 2008 |volume=7 |issue=1 |pages=13–6 |pmid=18246693 }}</ref> Treatment twice daily for six months is necessary, and is as effective as topical benzoyl peroxide 5%, isotretinoin 0.05%, and erythromycin 2%.<ref name=Herb2010>{{cite journal | vauthors = Morelli V, Calmet E, Jhingade V | title = Alternative therapies for common dermatologic disorders, part 2 | journal = Primary Care | volume = 37 | issue = 2 | pages = 285–96 | date = June 2010 | pmid = 20493337 | doi = 10.1016/j.pop.2010.02.005 | type = Review }}</ref> Azelaic acid is an effective acne treatment due to its ability to reduce skin cell accumulation in the follicle and its [[antibacterial]] and [[anti-inflammation|anti-inflammatory]] properties.<ref name=Sieber2014/> It has a slight skin-lightening effect due to its ability to inhibit melanin synthesis. Therefore, it is useful in treating individuals with acne who are also affected by post-inflammatory hyperpigmentation.<ref name=Vary2015/> Azelaic acid may cause skin irritation.<ref>{{MedlinePlusEncyclopedia|603020|Azelaic Acid Topical}}</ref> It is less effective and more expensive than retinoids.<ref name=Vary2015/> Azelaic acid also led to worse treatment response when compared to benzoyl peroxide. When compared to tretinoin, azelaic acid makes little or no treatment response.<ref>{{cite journal |last1=Liu |first1=Haibo |last2=Yu |first2=Haiyan |last3=Xia |first3=Jun |last4=Liu |first4=Ling |last5=Liu |first5=Guan J |last6=Sang |first6=Hong |last7=Peinemann |first7=Frank |date=2020-05-01 |editor-last=Cochrane Skin Group |title=Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acid (alpha-hydroxy acid) for acne |journal=Cochrane Database of Systematic Reviews |volume=5 |issue=5 |pages=CD011368 |doi=10.1002/14651858.CD011368.pub2 |pmc=7193765 |pmid=32356369}}</ref> ====Salicylic acid==== [[Salicylic acid]] is a topically applied [[beta-hydroxy acid]] that [[Bacteriostatic agent|stops bacteria from reproducing]] and has keratolytic properties.<ref name=Madan2014/><ref name=Well2013>{{cite journal | vauthors = Well D | title = Acne vulgaris: A review of causes and treatment options | journal = The Nurse Practitioner | volume = 38 | issue = 10 | pages = 22–31; quiz 32 | date = October 2013 | pmid = 24048347 | doi = 10.1097/01.NPR.0000434089.88606.70 | type = Review | doi-access = free }}</ref> It is less effective than retinoid therapy.<ref name=BMJ2013/> Salicylic acid opens obstructed skin pores and promotes the shedding of epithelial skin cells.<ref name=Madan2014>{{cite journal | vauthors = Madan RK, Levitt J | title = A review of toxicity from topical salicylic acid preparations | journal = Journal of the American Academy of Dermatology | volume = 70 | issue = 4 | pages = 788–792 | date = April 2014 | pmid = 24472429 | doi = 10.1016/j.jaad.2013.12.005 | type = Review }}</ref> [[Xerosis|Dry skin]] is the most commonly seen side effect with topical application, though [[hyperpigmentation|darkening]] of the skin can occur in individuals with darker skin types.<ref name=Vary2015/> ====Other medications==== Topical and oral preparations of [[nicotinamide]] (the [[amide]] form of [[Niacin (nutrient)|vitamin B<sub>3</sub>]]) are alternative medical treatments.<ref name=Rolfe2014>{{cite journal | vauthors = Rolfe HM | title = A review of nicotinamide: treatment of skin diseases and potential side effects | journal = Journal of Cosmetic Dermatology | volume = 13 | issue = 4 | pages = 324–8 | date = December 2014 | pmid = 25399625 | doi = 10.1111/jocd.12119 | s2cid = 28160151 | type = Review }}</ref> Nicotinamide reportedly improves acne due to its anti-inflammatory properties<ref name=Rolfe2014/> (influencing neutrophil [[chemotaxis]], inhibiting the release of histamine, suppressing the lymphocyte transformation test, and reducing nitric oxide synthase production induced by cytokines),<ref name="pmid38725769"/> its ability to suppress sebum production, and its wound healing properties.<ref name=Rolfe2014/> Topical and oral preparations of zinc are suggested treatments for acne; evidence to support their use for this purpose is limited.<ref name=Brandt2013>{{cite journal | vauthors = Brandt S | title = The clinical effects of zinc as a topical or oral agent on the clinical response and pathophysiologic mechanisms of acne: a systematic review of the literature | journal = Journal of Drugs in Dermatology | volume = 12 | issue = 5 | pages = 542–5 | date = May 2013 | pmid = 23652948 | type = Review }}</ref> Zinc's capacities to reduce inflammation and sebum production as well as inhibit ''C. acnes'' growth are its proposed mechanisms for improving acne.<ref name=Brandt2013/> [[Antihistamines]] may improve symptoms among those already taking isotretinoin due to their anti-inflammatory properties and their ability to suppress sebum production.<ref name=DC2016>{{cite journal | vauthors = Layton AM | title = Top Ten List of Clinical Pearls in the Treatment of Acne Vulgaris | journal = Dermatologic Clinics | volume = 34 | issue = 2 | pages = 147–57 | date = April 2016 | pmid = 27015774 | doi = 10.1016/j.det.2015.11.008 | type = Review }}</ref> [[Hydroquinone]] lightens the skin when applied topically by inhibiting [[tyrosinase]], the enzyme responsible for converting the amino acid [[tyrosine]] to the skin pigment [[melanin]], and is used to treat acne-associated post-inflammatory hyperpigmentation.<ref name="Chandra2012"/> By interfering with the production of melanin in the [[epidermis]], hydroquinone leads to less hyperpigmentation as darkened skin cells are naturally shed over time.<ref name="Chandra2012"/> Improvement in skin [[hyperpigmentation]] is typically seen within six months when used twice daily. Hydroquinone is ineffective for hyperpigmentation affecting deeper layers of skin such as the [[dermis]].<ref name="Chandra2012"/> The use of a [[sunscreen]] with [[Sun protection factor|SPF]] 15 or higher in the morning with reapplication every two hours is recommended when using hydroquinone.<ref name="Chandra2012"/> Its application only to affected areas lowers the risk of lightening the color of normal skin but can lead to a temporary ring of lightened skin around the hyperpigmented area.<ref name="Chandra2012"/> Hydroquinone is generally well-tolerated; side effects are typically mild (e.g., skin irritation) and occur with the use of a higher than the recommended 4% concentration.<ref name="Chandra2012"/> Most preparations contain the preservative [[sodium metabisulfite]], which has been linked to rare cases of [[allergic reaction]]s, including [[anaphylaxis]] and severe [[asthma]] exacerbations in susceptible people.<ref name="Chandra2012"/> In extremely rare cases, the frequent and improper application of high-dose hydroquinone has been associated with a systemic condition known as [[exogenous ochronosis]] (skin discoloration and [[connective tissue]] damage from the accumulation of [[homogentisic acid]]).<ref name="Chandra2012"/> ====Combination therapy==== Combination therapy—using medications of different classes together, each with a different mechanism of action—has been demonstrated to be a more effective approach to acne treatment than monotherapy.<ref name="Aslam2015"/><ref name=Kong2013/> The use of topical benzoyl peroxide and [[antibiotic]]s together is more effective than antibiotics alone.<ref name="Aslam2015"/> Similarly, using a topical retinoid with an antibiotic clears acne lesions faster than the use of antibiotics alone.<ref name="Aslam2015"/> Frequently used combinations include the following: antibiotic and benzoyl peroxide, antibiotic and topical retinoid, or topical retinoid and benzoyl peroxide.<ref name=Kong2013/> Dermatologists generally prefer combining benzoyl peroxide with a retinoid over the combination of a topical antibiotic with a retinoid. Both regimens are effective, but benzoyl peroxide does not lead to antibiotic resistance.<ref name="Aslam2015"/> ===Pregnancy=== Although sebaceous gland activity in the skin increases during the late stages of pregnancy, pregnancy has not been reliably associated with worsened acne severity.<ref name="Tyler2015"/> In general, topically applied medications are considered the first-line approach to acne treatment during pregnancy, as they have little systemic absorption and are therefore unlikely to harm a developing [[fetus]].<ref name="Tyler2015">{{cite journal | vauthors = Tyler KH | title = Dermatologic therapy in pregnancy | journal = Clinical Obstetrics and Gynecology | volume = 58 | issue = 1 | pages = 112–8 | date = March 2015 | pmid = 25517754 | doi = 10.1097/GRF.0000000000000089 | s2cid = 31034803 | type = Review }}</ref> Highly recommended therapies include topically applied [[benzoyl peroxide]] ([[pregnancy category]] C) and azelaic acid (category B).<ref name="Tyler2015"/> Salicylic acid carries a category C safety rating due to higher systemic absorption (9–25%), and an association between the use of anti-inflammatory medications in the third trimester and adverse effects to the developing fetus including [[oligohydramnios|too little amniotic fluid in the uterus]] and early closure of the babies' [[ductus arteriosus]] blood vessel.<ref name=Kong2013/><ref name="Tyler2015"/> Prolonged use of salicylic acid over significant areas of the skin or under [[occlusive dressing|occlusive (sealed) dressing]]s is not recommended as these methods increase systemic absorption and the potential for fetal harm.<ref name="Tyler2015"/> Tretinoin (category C) and adapalene (category C) are very poorly absorbed, but certain studies have suggested [[teratogen]]ic effects in the first trimester.<ref name="Tyler2015"/> The data examining the association between maternal topical retinoid exposure in the first trimester of pregnancy and adverse pregnancy outcomes is limited.<ref name="Kaplan2015">{{cite journal | vauthors = Kaplan YC, Ozsarfati J, Etwel F, Nickel C, Nulman I, Koren G | title = Pregnancy outcomes following first-trimester exposure to topical retinoids: a systematic review and meta-analysis | journal = The British Journal of Dermatology | volume = 173 | issue = 5 | pages = 1132–41 | date = November 2015 | pmid = 26215715 | doi = 10.1111/bjd.14053 | s2cid = 41362332 | type = Systematic Review & Meta-Analysis }}</ref> A systematic review of observational studies concluded that such exposure does not appear to increase the risk of major [[congenital malformations|birth defects]], [[Spontaneous abortion|miscarriages]], [[stillbirth]]s, [[premature birth]]s, or [[low birth weight]].<ref name="Kaplan2015"/> Similarly, in studies examining the effects of topical retinoids during pregnancy, fetal harm has not been seen in the second and third trimesters.<ref name="Tyler2015"/> Nevertheless, since rare harms from topical retinoids are not ruled out, they are not recommended for use during pregnancy due to persistent safety concerns.<ref name="Kaplan2015"/><ref name="Meredith2013">{{cite journal | vauthors = Meredith FM, Ormerod AD | title = The management of acne vulgaris in pregnancy | journal = American Journal of Clinical Dermatology | volume = 14 | issue = 5 | pages = 351–8 | date = October 2013 | pmid = 23996075 | doi = 10.1007/s40257-013-0041-9 | s2cid = 13637965 | type = Review }}</ref> Retinoids contraindicated for use during pregnancy include the topical retinoid tazarotene, and oral retinoids isotretinoin and [[acitretin]] (all category X).<ref name="Tyler2015"/> Spironolactone is relatively contraindicated for use during pregnancy due to its antiandrogen effects.<ref name=Vary2015/> Finasteride is not recommended as it is highly teratogenic.<ref name=Vary2015/> Topical antibiotics deemed safe during pregnancy include clindamycin, erythromycin, and metronidazole (all category B), due to negligible systemic absorption.<ref name=Kong2013/><ref name="Tyler2015"/> [[Nadifloxacin]] and dapsone (category C) are other topical antibiotics that may be used to treat acne in pregnant women but have received less study.<ref name=Kong2013/><ref name="Tyler2015"/> No adverse fetal events have been reported from the topical use of dapsone.<ref name="Tyler2015"/> If retinoids are used there is a high risk of abnormalities occurring in the developing fetus; women of childbearing age are therefore required to use effective [[birth control]] if retinoids are used to treat acne.<ref name=BMJ2013/> Oral antibiotics deemed safe for pregnancy (all category B) include [[azithromycin]], [[cephalosporin]]s, and [[penicillin]]s.<ref name="Tyler2015"/> Tetracyclines (category D) are contraindicated during pregnancy as they are known to deposit in developing fetal teeth, resulting in yellow discoloration and [[enamel hypoplasia|thinned tooth enamel]].<ref name=Vary2015/><ref name="Tyler2015"/> Their use during pregnancy has been associated with the development of [[acute fatty liver of pregnancy]] and is further avoided for this reason.<ref name="Tyler2015"/> ===Procedures=== Limited evidence supports [[comedo extraction]], but it is an option for comedones that do not improve with standard treatment.<ref name=Titus2012/><ref name="Zaenglein2016"/> Another procedure for immediate relief is the injection of a corticosteroid into an inflamed acne comedo.<ref name="Zaenglein2016"/> [[Electrocautery]] and [[electrofulguration]] are effective alternative treatments for comedones.<ref>{{cite book| vauthors = Bolognia JL, Jorizzo JL |title=Dermatology |date=2012 |publisher=Mosby Elsevier|location=St. Louis, Mo. |isbn=9780702051821 |edition=3rd |page=558}}</ref> [[Light therapy]] is a treatment method that involves delivering certain specific wavelengths of light to an area of skin affected by acne. Both regular and [[laser light]] have been used. The evidence for [[light therapy]] as a treatment for acne is weak and inconclusive.<ref name="Titus2012"/><ref name="Posadzki2018">{{cite journal | vauthors = Posadzki P, Car J | title = Light Therapies for Acne | journal = JAMA Dermatology | volume = 154 | issue = 5 | pages = 597–598 | date = May 2018 | pmid = 29541753 | doi = 10.1001/jamadermatol.2018.0110 }}</ref> Various light therapies appear to provide a short-term benefit, but data for long-term outcomes, and outcomes in those with severe acne, are sparse;<ref name="Hamil2009">{{cite journal | vauthors = Hamilton FL, Car J, Lyons C, Car M, Layton A, Majeed A | title = Laser and other light therapies for the treatment of acne vulgaris: systematic review | journal = The British Journal of Dermatology | volume = 160 | issue = 6 | pages = 1273–85 | date = June 2009 | pmid = 19239470 | doi = 10.1111/j.1365-2133.2009.09047.x | s2cid = 6902995 | type = Systematic Review & Meta-Analysis }}</ref> it may have a role for individuals whose acne has been resistant to topical medications.<ref name="Aslam2015" /> A 2016 meta-analysis was unable to conclude whether light therapies were more beneficial than placebo or no treatment, nor the duration of benefit.<ref>{{cite journal | vauthors = Barbaric J, Abbott R, Posadzki P, Car M, Gunn LH, Layton AM, Majeed A, Car J | display-authors = 6 | title = Light therapies for acne | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD007917 | date = September 2016 | issue = 9 | pmid = 27670126 | pmc = 6457763 | doi = 10.1002/14651858.CD007917.pub2 }}</ref> When regular light is used immediately following the application of a [[photosensitizer|sensitizing substance]] to the skin such as [[aminolevulinic acid]] or [[methyl aminolevulinate]], the treatment is referred to as [[photodynamic therapy]] (PDT).<ref name="Barbieri2019"/><ref name="Pugashetti2013">{{cite journal | vauthors = Pugashetti R, Shinkai K | title = Treatment of acne vulgaris in pregnant patients | journal = Dermatologic Therapy | volume = 26 | issue = 4 | pages = 302–11 | date = July 2013 | pmid = 23914887 | doi = 10.1111/dth.12077 | s2cid = 5750718 | type = Review | doi-access = free }}</ref> PDT has the most supporting evidence of all light therapy modalities.<ref name="Zaenglein2016" /> PDT treats acne by using various forms of light (e.g., blue light or red light) that preferentially target the pilosebaceous unit.<ref name="Barbieri2019"/> Once the light activates the sensitizing substance, this generates [[free radicals]] and [[reactive oxygen species]] in the skin, which purposefully damage the sebaceous glands and kill ''C. acnes'' bacteria.<ref name="Barbieri2019"/> Many different types of nonablative lasers (i.e., lasers that do not vaporize the top layer of the skin but rather induce a physiologic response in the skin from the light) have been used to treat acne, including those that use infrared wavelengths of light. Ablative lasers (such as [[Carbon dioxide laser|CO<sub>2</sub>]] and fractional types) have also been used to treat active acne and its scars. When ablative lasers are used, the treatment is often referred to as [[laser resurfacing]] because, as mentioned previously, the entire upper layers of the skin are vaporized.<ref name="Cohen2016"/> Ablative lasers are associated with higher rates of adverse effects compared with non-ablative lasers, with examples being post-inflammatory hyperpigmentation, persistent facial redness, and persistent pain.<ref name=Titus2012/><ref name=Ong2012>{{cite journal | vauthors = Ong MW, Bashir SJ | title = Fractional laser resurfacing for acne scars: a review | journal = The British Journal of Dermatology | volume = 166 | issue = 6 | pages = 1160–9 | date = June 2012 | pmid = 22296284 | doi = 10.1111/j.1365-2133.2012.10870.x | s2cid = 205262673 | type = Review }}</ref><ref name="Abdel2016">{{cite journal | vauthors = Abdel Hay R, Shalaby K, Zaher H, Hafez V, Chi CC, Dimitri S, Nabhan AF, Layton AM | display-authors = 6 | title = Interventions for acne scars | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD011946 | date = April 2016 | issue = 4 | pmid = 27038134 | doi = 10.1002/14651858.CD011946.pub2 | type = Systematic Review & Meta-Analysis | pmc = 7069546 }}</ref> Physiologically, certain wavelengths of light, used with or without accompanying topical chemicals, are thought to kill bacteria and decrease the size and activity of the glands that produce sebum.<ref name="Pugashetti2013"/> Disadvantages of light therapy can include its cost, the need for multiple visits, the time required to complete the procedure(s), and pain associated with some of the treatment modalities.<ref name="Aslam2015"/> Typical side effects include [[desquamation|skin peeling]], temporary reddening of the skin, swelling, and post-inflammatory hyperpigmentation.<ref name="Aslam2015" /> ====Postacne scar treatment==== [[Dermabrasion]] is an effective therapeutic procedure for reducing the appearance of superficial atrophic scars of the boxcar and rolling varieties.<ref name="Levy2012"/> Ice-pick scars do not respond well to treatment with dermabrasion due to their depth.<ref name="Levy2012"/> The procedure is painful and has many potential side effects such as skin sensitivity to sunlight, [[erythema|redness]], and [[Hypopigmentation|decreased pigmentation of the skin]].<ref name="Levy2012"/> Dermabrasion has fallen out of favor with the introduction of laser resurfacing.<ref name="Levy2012"/> Unlike dermabrasion, there is no evidence that [[microdermabrasion]] is an effective treatment for acne.<ref name="Titus2012"/> Dermal or subcutaneous [[Injectable filler|filler]]s are substances injected into the skin to improve the appearance of acne scars. Fillers are used to increase natural [[collagen]] production in the skin and to increase skin volume and decrease the depth of acne scars.<ref name="Soliman2018">{{cite journal | vauthors = Soliman YS, Horowitz R, Hashim PW, Nia JK, Farberg AS, Goldenberg G | title = Update on acne scar treatment | journal = Cutis | volume = 102 | issue = 1 | pages = 21;25;47;48 | date = July 2018 | pmid = 30138491 | url = https://www.mdedge.com/cutis/article/169785/acne/update-acne-scar-treatment | type = Review | access-date = 19 September 2018 | archive-url = https://web.archive.org/web/20180919132148/https://www.mdedge.com/cutis/article/169785/acne/update-acne-scar-treatment | archive-date = 19 September 2018 | url-status = live }}</ref> Examples of fillers used for this purpose include [[hyaluronic acid]]; [[poly(methyl methacrylate)]] [[microsphere]]s with collagen; human and bovine collagen derivatives, and fat harvested from the person's own body (autologous fat transfer).<ref name="Soliman2018"/> [[Microneedling]] is a procedure in which an instrument with multiple rows of tiny needles is rolled over the skin to elicit a wound healing response and stimulate collagen production to reduce the appearance of atrophic acne scars in people with darker skin color.<ref name="Cohen2016">{{cite journal | vauthors = Cohen BE, Elbuluk N | title = Microneedling in skin of color: A review of uses and efficacy | journal = Journal of the American Academy of Dermatology | volume = 74 | issue = 2 | pages = 348–55 | date = February 2016 | pmid = 26549251 | doi = 10.1016/j.jaad.2015.09.024 | type = Review }}</ref> Notable adverse effects of microneedling include post-inflammatory hyperpigmentation and tram track scarring (described as discrete slightly raised scars in a linear distribution similar to a tram track). The latter is thought to be primarily attributable to improper technique by the practitioner, including the use of excessive pressure or inappropriately large needles.<ref name="Cohen2016"/><ref name="Pahwa2012">{{cite journal | vauthors = Pahwa M, Pahwa P, Zaheer A | title = "Tram track effect" after treatment of acne scars using a microneedling device | journal = Dermatologic Surgery | volume = 38 | issue = 7 Pt 1 | pages = 1107–8 | date = July 2012 | pmid = 22587597 | doi = 10.1111/j.1524-4725.2012.02441.x | type = Case Report & Literature Review }}</ref> A clinical study assessing the efficacy of microneedling vis-à-vis with application of topical [[tazarotene]] gel, 0.1% in the treatment of postacne facial scars, found that tazarotene gel when applied for a period of three to six months once every night, resulted in significant improvement of atrophic scars similar to microneedling.<ref name="Tazarotene">{{cite journal |last1=Afra |first1=TP |last2=Razmi |first2=T M |last3=Narang |first3=T |last4=Dogra |first4=S |last5=Kumar |first5=A |title=Topical Tazarotene Gel, 0.1%, as a Novel Treatment Approach for Atrophic Postacne Scars: A Randomized Active-Controlled Clinical Trial |journal=JAMA Facial Plast Surg |date=2019 |volume=21 |issue=2 |pages=125–132 |doi=10.1001/jamafacial.2018.1404 |pmid=30452511|pmc=6439800 }}</ref> [[Subcision]] is useful for the treatment of superficial atrophic acne scars and involves the use of a small needle to loosen the fibrotic adhesions that result in the depressed appearance of the scar.<ref>{{cite journal | vauthors = Lanoue J, Goldenberg G | title = Acne scarring: a review of cosmetic therapies | journal = Cutis | volume = 95 | issue = 5 | pages = 276–81 | date = May 2015 | pmid = 26057505 | type = Review }}</ref><ref>{{cite journal | vauthors = Kroepfl L, Emer JJ | title = Combination Therapy for Acne Scarring: Personal Experience and Clinical Suggestions | journal = Journal of Drugs in Dermatology | volume = 15 | issue = 11 | pages = 1413–1419 | date = November 2016 | pmid = 28095556 | type = Review }}</ref><ref>{{cite journal | vauthors = Zaleski-Larsen LA, Fabi SG, McGraw T, Taylor M | title = Acne Scar Treatment: A Multimodality Approach Tailored to Scar Type | journal = Dermatologic Surgery | volume = 42 Suppl 2 | issue = Supplement 2 | pages = S139-49 | date = May 2016 | pmid = 27128240 | doi = 10.1097/DSS.0000000000000746 | s2cid = 25638674 | type = Review }}</ref> [[Chemical peel]]s can be used to reduce the appearance of acne scars.<ref name=Levy2012/> Mild peels include those using [[glycolic acid]], [[lactic acid]], [[salicylic acid]], [[Jessner's solution]], or a lower concentration (20%) of [[trichloroacetic acid]]. These peels only affect the [[epidermis|epidermal layer of the skin]] and can be useful in the treatment of superficial acne scars as well as skin pigmentation changes from inflammatory acne.<ref name=Levy2012/> Higher concentrations of trichloroacetic acid (30–40%) are considered to be medium-strength peels and affect the skin as deep as the [[Dermis#Stratum papillare|papillary dermis]].<ref name=Levy2012/> Formulations of trichloroacetic acid concentrated to 50% or more are considered to be deep chemical peels.<ref name=Levy2012/> Medium-strength and deep-strength chemical peels are more effective for deeper atrophic scars but are more likely to cause side effects such as skin pigmentation changes, infection, and [[Milium (dermatology)|small white superficial cysts known as milia]].<ref name=Levy2012/> ===Alternative medicine=== Researchers are investigating complementary therapies as treatment for people with acne.<ref name="CaoYang2015">{{cite journal | vauthors = Cao H, Yang G, Wang Y, Liu JP, Smith CA, Luo H, Liu Y | title = Complementary therapies for acne vulgaris | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD009436 | date = January 2015 | issue = 1 | pmid = 25597924 | pmc = 4486007 | doi = 10.1002/14651858.CD009436.pub2 | type = Systematic Review & Meta-Analysis }}</ref> [[Evidence-based medicine#Assessing the quality of evidence|Low-quality evidence]] suggests topical application of [[tea tree oil]] or [[bee venom]] may reduce the total number of skin lesions in those with acne.<ref name="CaoYang2015"/> Tea tree oil appears to be approximately as effective as [[benzoyl peroxide]] or salicylic acid but is associated with [[allergic contact dermatitis]].<ref name=Vary2015/> Proposed mechanisms for tea tree oil's anti-acne effects include antibacterial action against ''C. acnes'' and anti-inflammatory properties.<ref name=Hammer2015/> Numerous other plant-derived therapies have demonstrated positive effects against acne (e.g., [[basil oil]]; [[oligosaccharide]]s from [[seaweed]]; however, few well-done studies have examined their use for this purpose.<ref name="Fisk2014">{{cite journal | vauthors = Fisk WA, Lev-Tov HA, Sivamani RK | title = Botanical and phytochemical therapy of acne: a systematic review | journal = Phytotherapy Research | volume = 28 | issue = 8 | pages = 1137–52 | date = August 2014 | pmid = 25098271 | doi = 10.1002/ptr.5125 | s2cid = 10111211 | type = Systematic Review }}</ref> There is a lack of high-quality evidence for the use of [[acupuncture]], [[Herbalism|herbal medicine]], or [[cupping therapy]] for acne.<ref name=CaoYang2015/> ===Self-care=== Many over-the-counter treatments in many forms are available, which are often known as [[cosmeceuticals]].<ref>{{cite journal | vauthors = Decker A, Graber EM | title = Over-the-counter Acne Treatments: A Review | journal = The Journal of Clinical and Aesthetic Dermatology | volume = 5 | issue = 5 | pages = 32–40 | date = May 2012 | pmid = 22808307 | pmc = 3366450 | type = Review }}</ref> Certain types of [[makeup]] may be useful to mask acne.<ref name=Good2009/> In those with oily skin, a water-based product is often preferred.<ref name=Good2009>{{cite journal | vauthors = Goodman G | title = Cleansing and moisturizing in acne patients | journal = American Journal of Clinical Dermatology | volume = 10 | issue = Suppl 1 | pages = 1–6 | date = 2009 | pmid = 19209947 | doi = 10.2165/0128071-200910001-00001 | s2cid = 36792285 | type = Review }}</ref><ref>{{cite book|last1=Bajaj|first1=Lalit|last2=Berman|first2=Stephen |title=Berman's Pediatric Decision Making|date=2011|publisher=Elsevier Health Sciences|isbn=978-0323054058|page=572|url=https://books.google.com/books?id=NPhnHrDQ1_kC&pg=PA572 |url-status=live|archive-url=https://web.archive.org/web/20170906210844/https://books.google.com/books?id=NPhnHrDQ1_kC&pg=PA572|archive-date=6 September 2017}}</ref> ==Prognosis== Acne usually improves around the age of 20 but may persist into adulthood.<ref name=Nurse09>{{cite journal | vauthors = Ramos-e-Silva M, Carneiro SC | title = Acne vulgaris: review and guidelines | journal = Dermatology Nursing | volume = 21 | issue = 2 | pages = 63–8; quiz 69 | date = March 2009 | pmid = 19507372 | type = Review }}</ref> Permanent physical scarring may occur.<ref name=BMJ2013/> Rare complications from acne or its treatment include the formation of [[pyogenic granulomas]], [[osteoma cutis]], and [[acne with facial edema]].<ref>{{cite book| first1 = George E | last1 = Andrews | first2 = Timothy G | last2 = Berger | first3 = Dirk M | last3 = Elston | first4 = William D | last4 = James |title=Andrews' Diseases of the skin : clinical dermatology.|url=https://archive.org/details/andrewsdiseasess00mdwi|url-access=limited|date=2011|publisher=Saunders/ Elsevier|location=[London]|isbn=9781437703146|page=[https://archive.org/details/andrewsdiseasess00mdwi/page/n242 234]|edition=11th}}</ref> Early and aggressive treatment of acne is advocated by some in the medical community to reduce the chances of these poor outcomes.<ref name="Goodman2006"/> === Mental health impact === There is good evidence to support the idea that acne and associated scarring negatively affect a person's psychological state, worsen mood, lower self-esteem, and are associated with a higher risk of [[anxiety disorders]], [[depression (mood)|depression]], and [[Suicidal ideation|suicidal thoughts]].<ref name="Barnes2012" /><ref name="Fife2016" /><ref name="Bhate2014" /><ref name=":2" /> Misperceptions about acne's causative and aggravating factors are common, and people with acne often blame themselves, and others often blame those with acne for their condition.<ref name="Goodman2006b">{{cite journal |last1=Goodman |first1=G |date=August 2006 |title=Acne--natural history, facts and myths |url=https://www.racgp.org.au/afp/200608/10602 |journal=Australian Family Physician |volume=35 |issue=8 |pages=613–616 |pmid=16894437 |access-date=16 April 2022 |archive-date=16 April 2022 |archive-url=https://web.archive.org/web/20220416133344/https://www.racgp.org.au/afp/200608/10602 |url-status=live }}</ref><ref name=":2" /> Such blame can worsen the affected person's sense of self-esteem.<ref name="Goodman2006b" /> Until the 20th century, even among dermatologists, the list of causes was believed to include excessive sexual thoughts and [[masturbation]].<ref name=":0" /> Dermatology's association with [[sexually transmitted infection]]s, especially [[syphilis]], contributed to the stigma.<ref name=":0" /> Another [[psychological]] complication of acne vulgaris is [[acne excoriée]], which occurs when a person persistently picks and scratches pimples, irrespective of the severity of their acne.<ref name="Rodriguez2014" /><ref>{{cite book |url=https://books.google.com/books?id=Hv8fBQAAQBAJ&pg=PT335 |title=Conn's Current Therapy 2015: Expert Consult – Online |vauthors=Bope ET, Kellerman RD |date=2014 |isbn=978-0-323-31956-0 |page=299 |publisher=Elsevier Health Sciences |archive-url=https://web.archive.org/web/20170906210844/https://books.google.com/books?id=Hv8fBQAAQBAJ&pg=PT335 |archive-date=6 September 2017 |url-status=live}}</ref> This can lead to significant scarring, changes in the affected person's skin pigmentation, and a cyclic worsening of the affected person's anxiety about their appearance.<ref name="Rodriguez2014" /> ==Epidemiology== Globally, acne affects approximately 650 million people, or about 9.4% of the population, as of 2010.<ref name=LancetEpi2012>{{cite journal | vauthors = Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, etal | title = Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010 | journal = Lancet | volume = 380 | issue = 9859 | pages = 2163–96 | date = December 2012 | pmid = 23245607 | pmc = 6350784 | doi = 10.1016/S0140-6736(12)61729-2 }}</ref> It affects nearly 90% of people in Western societies during their teenage years, but can occur before adolescence and may persist into adulthood.<ref name="Taylor2011"/><ref name=BMJ2013/><ref name="ReferenceB"/> While acne that first develops between the ages of 21 and 25 is uncommon, it affects 54% of women and 40% of men older than 25 years of age<ref name=Kong2013/><ref name=Holzmann2013>{{cite journal | vauthors = Holzmann R, Shakery K | title = Postadolescent acne in females | journal = Skin Pharmacology and Physiology | volume = 27 Suppl 1 | issue = Supplement 1 | pages = 3–8 | date = November 2013 | pmid = 24280643 | doi = 10.1159/000354887 | s2cid = 40314598 | type = Review }}</ref> and has a lifetime prevalence of 85%.<ref name=Kong2013/> About 20% of those affected have moderate or severe cases.<ref name="Bhate2013"/> It is slightly more common in females than males (9.8% versus 9.0%).<ref name=LancetEpi2012/> In those over 40 years old, 1% of males and 5% of females still have problems.<ref name=BMJ2013/> Rates appear to be lower in rural societies.<ref name="Spen2009"/> While some research has found it affects people of all ethnic groups,<ref name=Shah2010>{{cite journal | vauthors = Shah SK, Alexis AF | title = Acne in skin of color: practical approaches to treatment | journal = The Journal of Dermatological Treatment | volume = 21 | issue = 3 | pages = 206–11 | date = May 2010 | pmid = 20132053 | doi = 10.3109/09546630903401496 | s2cid = 27893826 | type = Review }}</ref> acne may not occur in the non-Westernized peoples of [[Papua New Guinea]] and [[Paraguay]].<ref name="Tan2015">{{cite journal |last1=Tan |first1=J.K.L. |last2=Bhate |first2=K. |title=A global perspective on the epidemiology of acne |journal=British Journal of Dermatology |date=July 2015 |volume=172 |issue=Supplement 1 |pages=3–12 |doi=10.1111/bjd.13462 |pmid=25597339 |s2cid=19433549 |type=Review |doi-access= }}</ref> Acne affects 40–50 million people in the United States (16%) and approximately 3–5 million in Australia (23%).<ref name=Koo2014/><ref>{{cite journal | vauthors = White GM | title = Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris | journal = Journal of the American Academy of Dermatology | volume = 39 | issue = 2 Pt 3 | pages = S34-7 | date = August 1998 | pmid = 9703121 | doi = 10.1016/S0190-9622(98)70442-6 | type = Review }}</ref> Severe acne tends to be more common in people of Caucasian or Amerindian descent than in people of African descent.<ref name="Goldberg2011"/> ==History== [[File:Jar of 'Domolene' ointment, London, England, 1945-1965 Wellcome L0058221.jpg|thumb|upright|[[Domolene]] ointment, a mid-1900s medication that was claimed to cure acne|alt=A jar of ointment, with a box and a poster. The box has the words "Domolene Brand Stops all skin troubles rashes and irritation The miracle ointment".]] Historical records indicate that [[pharaoh]]s had acne, which may be the earliest known reference to the disease. [[Sulfur]]'s usefulness as a topical remedy for acne dates back to at least the reign of [[Cleopatra]] (69–30 BCE).<ref name="Keri2009">{{cite journal | vauthors = Keri J, Shiman M | title = An update on the management of acne vulgaris | journal = Clinical, Cosmetic and Investigational Dermatology | volume = 2 | pages = 105–10 | date = June 2009 | doi = 10.2147/ccid.s3630 |doi-access=free | pmid = 21436973 | pmc = 3047935 | type = Review }}</ref> The sixth-century [[Greece|Greek]] physician [[Aëtius of Amida]] reportedly coined the term "{{lang|grc-Latn|ionthos}}" ({{lang|grc|ίονθωξ}},) or "{{lang|grc-Latn|acnae}}", which seems to be a reference to facial skin lesions that occur during "the '[[wikt:acme|acme]]' of life" ([[puberty]]).<ref name="Tilles2014">{{cite journal | vauthors = Tilles G | title = Acne pathogenesis: history of concepts | journal = Dermatology | volume = 229 | issue = 1 | pages = 1–46 | date = September 2014 | pmid = 25228295 | doi = 10.1159/000364860 | s2cid = 32660371 | type = Review }}</ref> In the 16th century, the French physician and botanist [[François Boissier de Sauvages de Lacroix]] provided one of the earlier descriptions of acne. He used the term "psydracia achne" to describe small, red, and hard [[Tubercle (anatomy)|tubercles]] that altered a person's facial appearance during adolescence and were neither itchy nor painful.<ref name="Tilles2014" /> The recognition and characterization of acne progressed in 1776 when [[Josef Plenck]] (an [[Austria]]n physician) published a book that proposed the novel concept of classifying skin diseases by their elementary (initial) lesions.<ref name="Tilles2014" /> In 1808 the [[England|English]] [[dermatologist]] [[Robert Willan]] refined Plenck's work by providing the first detailed descriptions of several skin disorders using morphologic terminology that remains in use today.<ref name="Tilles2014" /> [[Thomas Bateman (physician)|Thomas Bateman]] continued and expanded on Robert Willan's work as his student and provided the first descriptions and illustrations of acne accepted as accurate by modern dermatologists.<ref name="Tilles2014" /> [[Erasmus Wilson]], in 1842, was the first to make the distinction between acne vulgaris and rosacea.<ref>{{cite book| vauthors = Bolognia JL, Jorizzo JL |title=Dermatology|date=2012|publisher=Mosby Elsevier|location=St. Louis, Mo.|isbn=9780702051821|edition=3rd|page=545}}</ref> The first professional medical [[monograph]] dedicated entirely to acne was written by [[Lucius Duncan Bulkley]] and published in New York in 1885.<ref name=":0">{{cite book|chapter-url=https://books.google.com/books?id=S-rNTj6IlVAC|title=The Body Project: An Intimate History of American Girls|last=Brumberg|first=Joan Jacobs |date=9 June 2010|publisher=Knopf Doubleday Publishing Group|isbn=9780307755742|pages=57–94 |chapter=Perfect Skin|url-status=live|archive-url=https://web.archive.org/web/20170312063855/https://books.google.com/books?id=S-rNTj6IlVAC|archive-date=12 March 2017}}</ref><ref>{{cite book|url=https://archive.org/details/acneitsetiology00bulkgoog|title=Acne; Its Etiology, Pathology and Treatment|last=Bulkley|first=Lucius Duncan|publisher=G.P. Putnam's Sons|date=1885|location=New York |access-date=15 February 2020|archive-url=https://web.archive.org/web/20160505114832/https://archive.org/details/acneitsetiology00bulkgoog|archive-date=5 May 2016|url-status=live}}</ref> Scientists initially hypothesized that acne represented a disease of the skin's hair follicle, and occurred due to blockage of the pore by sebum. During the 1880s, they observed bacteria by microscopy in skin samples from people with acne. Investigators believed the bacteria caused comedones, sebum production, and ultimately acne.<ref name="Tilles2014" /> During the mid-twentieth century, dermatologists realized that no single hypothesized factor (sebum, bacteria, or excess keratin) fully accounted for the disease in its entirety.<ref name="Tilles2014" /> This led to the current understanding that acne could be explained by a sequence of related events, beginning with blockage of the skin follicle by excessive dead skin cells, followed by bacterial invasion of the hair follicle pore, changes in sebum production, and inflammation.<ref name="Tilles2014" /> The approach to acne treatment underwent significant changes during the twentieth century. Retinoids became a medical treatment for acne in 1943.<ref name="Riahi2016" /> Benzoyl peroxide was first proposed as a treatment in 1958 and remains a staple of acne treatment.<ref name="Dutil2010">{{cite journal | vauthors = Dutil M | title = Benzoyl peroxide: enhancing antibiotic efficacy in acne management | journal = Skin Therapy Letter | volume = 15 | issue = 10 | pages = 5–7 | date = November–December 2010 | pmid = 21076800 | url = http://www.skintherapyletter.com/2010/15.10/2.html | url-status = live | type = Review | archive-url = https://web.archive.org/web/20170227150410/http://www.skintherapyletter.com/2010/15.10/2.html | archive-date = 27 February 2017 }}</ref> The introduction of oral tetracycline antibiotics (such as minocycline) modified acne treatment in the 1950s. These reinforced the idea amongst dermatologists that bacterial growth on the skin plays an important role in causing acne.<ref name="Tilles2014" /> Subsequently, in the 1970s, [[tretinoin]] (original trade name Retin A) was found to be an effective treatment.<ref name="pmid4265099">{{cite journal | title = Tretinoin (retinoic acid) in acne | journal = The Medical Letter on Drugs and Therapeutics | volume = 15 | issue = 1 | pages = 3 | date = January 1973 | pmid = 4265099 }}</ref> The development of oral [[isotretinoin]] (sold as Accutane and Roaccutane) followed.<ref name="pmid6107678">{{cite journal | vauthors = Jones H, Blanc D, Cunliffe WJ | title = 13-cis retinoic acid and acne | journal = Lancet | volume = 2 | issue = 8203 | pages = 1048–9 | date = November 1980 | pmid = 6107678 | doi = 10.1016/S0140-6736(80)92273-4 | s2cid = 40877032 }}</ref> After its introduction in the United States in 1982,<ref name="pmid20482692">{{cite journal |vauthors=Ganceviciene R, Zouboulis CC |title=Isotretinoin: state of the art treatment for acne vulgaris |journal=Journal of the German Society of Dermatology |volume=8 Suppl 1 |issue= |pages=S47–59 |date=March 2010 |pmid=20482692 |doi=10.1111/j.1610-0387.2009.07238.x |quote=Since its approval by the US FDA in 1982, isotretinoin has been considered a breakthrough treatment against severe nodular and/or cystic acne, a challenging form of acne that affects thousands of young people worldwide at a time when they may feel most vulnerable and sensitive to social and physical environmental changes.}}</ref> scientists identified isotretinoin as a medication highly likely to cause birth defects if taken during pregnancy. In the United States, more than 2,000 women became pregnant while taking isotretinoin between 1982 and 2003, with most pregnancies ending in [[abortion]] or [[miscarriage]]. Approximately 160 babies were born with birth defects due to maternal use of isotretinoin during pregnancy.<ref name="pmid17214828">{{cite journal | vauthors = Bérard A, Azoulay L, Koren G, Blais L, Perreault S, Oraichi D | title = Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective | journal = British Journal of Clinical Pharmacology | volume = 63 | issue = 2 | pages = 196–205 | date = February 2007 | pmid = 17214828 | pmc = 1859978 | doi = 10.1111/j.1365-2125.2006.02837.x }}</ref><ref name="pmid9580798">{{cite journal | vauthors = Holmes SC, Bankowska U, Mackie RM | title = The prescription of isotretinoin to women: is every precaution taken? | journal = The British Journal of Dermatology | volume = 138 | issue = 3 | pages = 450–5 | date = March 1998 | pmid = 9580798 | doi = 10.1046/j.1365-2133.1998.02123.x | s2cid = 46287015 }}</ref> Treatment of acne with topical crushed dry ice, known as cryoslush, was first described in 1907 but is no longer performed commonly.<ref>{{cite journal | vauthors = Green RG | title = No soap and dry ice or a treatment for acne | journal = Canadian Family Physician | volume = 14 | issue = 5 | pages = 21–2 | date = May 1968 | pmid = 20468218 | pmc = 2281078 }}</ref> Before 1960, the use of X-rays was also a common treatment.<ref>{{cite journal | vauthors = Semon HC | journal = British Medical Journal | volume = 1 | issue = 3099 | pages = 700–2 | date = May 1920 | pmid = 20769902 | pmc = 2337520 | doi = 10.1136/bmj.1.3099.700 | type = Review | title = The X-Ray Treatment of Acne Vulgaris }}</ref><ref>{{cite journal|title=Acne Vulgaris and X-Ray Treatment|journal=The New England Journal of Medicine|date=December 1938|volume=219|issue=24|pages=971|doi=10.1056/NEJM193812152192414}}</ref> ==Society and culture== The costs and social impact of acne are substantial. In the United States, acne vulgaris is responsible for more than 5 million [[physician|doctor]] visits and costs over {{currency|2.5|USD}} billion each year in [[Variable cost|direct costs]].<ref name="Knutsen2012"/> Similarly, acne vulgaris is responsible for 3.5 million doctor visits each year in the [[United Kingdom]].<ref name=BMJ2013/> Sales for the top ten leading acne treatment brands in the US in 2015 amounted to $352{{nbsp}}million.<ref>{{cite web|url= https://www.statista.com/statistics/448473/leading-us-acne-brands/|title= Sales of the leading acne brands in the United States in 2015 (in million U.S. dollars)|author= <!--Not stated-->|publisher= Statista Inc.|website= statista: The Statistics Portal|access-date= 12 March 2017|url-status= live|archive-url= https://web.archive.org/web/20170312195114/https://www.statista.com/statistics/448473/leading-us-acne-brands/|archive-date= 12 March 2017}}</ref> Acne vulgaris and its resultant scars are associated with significant social and academic difficulties that can last into adulthood.<ref name="Fife2016" /><ref name="Brown2013">{{cite journal | vauthors = Brown MM, Chamlin SL, Smidt AC | title = Quality of life in pediatric dermatology | journal = Dermatologic Clinics | volume = 31 | issue = 2 | pages = 211–21 | date = April 2013 | pmid = 23557650 | doi = 10.1016/j.det.2012.12.010 | type = Review }}</ref> During the [[Great Depression]], dermatologists discovered that young men with acne had difficulty obtaining jobs.<ref name=":0" /> Until the 1930s, many people viewed acne as a trivial problem among middle-class girls because, unlike [[smallpox]] and [[tuberculosis]], no one died from it, and a feminine problem, because boys were much less likely to seek medical assistance for it.<ref name=":0" /> During [[World War II]], some soldiers in tropical climates developed such severe and widespread [[tropical acne]] on their bodies that they were declared medically [[Selective Service System#Classifications|unfit for duty]].<ref name=":0" /> ==Research== Efforts to better understand the mechanisms of sebum production are underway. This research aims to develop medications that target and interfere with the hormones that are known to increase sebum production (e.g., [[IGF-1]] and [[alpha-melanocyte-stimulating hormone]]).<ref name="Aslam2015"/> Other sebum-lowering medications such as topical antiandrogens, [[peroxisome proliferator-activated receptor]] modulators, and inhibitors of the [[stearoyl-CoA desaturase-1]] [[enzyme]] are also a focus of research efforts.<ref name="Aslam2015"/><ref name="Barbieri2019"/> Particles that release [[nitric oxide]] into the skin to decrease skin inflammation caused by ''C. acnes'' and the [[immune system]] have shown promise for improving acne in early clinical trials.<ref name="Barbieri2019"/> Another avenue of early-stage research has focused on how to best use laser and light therapy to selectively destroy sebum-producing glands in the skin's hair follicles to reduce sebum production and improve acne appearance.<ref name="Aslam2015"/> The use of [[antimicrobial peptides]] against ''C. acnes'' is under investigation as a treatment for acne to overcoming antibiotic resistance.<ref name="Aslam2015"/> In 2007, scientists reported the first [[genome]] [[DNA sequencing|sequencing]] of a ''C. acnes'' [[bacteriophage]] (PA6). The authors proposed applying this research toward the development of [[phage therapy|bacteriophage therapy]] as an acne treatment to overcome the problems associated with long-term antibiotic use, such as bacterial resistance.<ref name=Farrar2007>{{cite journal | vauthors = Farrar MD, Howson KM, Bojar RA, West D, Towler JC, Parry J, Pelton K, Holland KT | display-authors = 6 | title = Genome sequence and analysis of a Propionibacterium acnes bacteriophage | journal = Journal of Bacteriology | volume = 189 | issue = 11 | pages = 4161–7 | date = June 2007 | pmid = 17400737 | pmc = 1913406 | doi = 10.1128/JB.00106-07 }}</ref> Oral and topical [[probiotic]]s are under evaluation as treatments for acne.<ref name=Baquerizo2014>{{cite journal | vauthors = Baquerizo Nole KL, Yim E, Keri JE | title = Probiotics and prebiotics in dermatology | journal = Journal of the American Academy of Dermatology | volume = 71 | issue = 4 | pages = 814–21 | date = October 2014 | pmid = 24906613 | doi = 10.1016/j.jaad.2014.04.050 | type = Review }}</ref> Probiotics may have therapeutic effects for those affected by acne due to their ability to decrease skin inflammation and improve skin moisture by increasing the skin's [[ceramide]] content.<ref name=Baquerizo2014/> As of 2014, knowledge of the effects of probiotics on acne in humans was limited.<ref name=Baquerizo2014/> Decreased levels of [[retinoic acid]] in the skin may contribute to comedo formation. Researchers are investigating methods to increase the skin's production of retinoic acid to address this deficiency.<ref name="Aslam2015"/> A [[vaccine]] against inflammatory acne has shown promising results in mice and humans.<ref name=Simonart2013/><ref>{{cite journal | vauthors = Liu PF, Hsieh YD, Lin YC, Two A, Shu CW, Huang CM | title = Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris | journal = Current Drug Metabolism | volume = 16 | issue = 4 | pages = 245–54 | date = 2015 | pmid = 26264195 | doi = 10.2174/1389200216666150812124801 | type = Review }}</ref> Some have voiced concerns about creating a vaccine designed to neutralize a stable community of normal skin bacteria that is known to protect the skin from colonization by more harmful microorganisms.<ref>{{cite magazine |date=23 September 2011 | vauthors = MacKenzie D | title=In development: a vaccine for acne|url=https://www.newscientist.com/article/dn20958-in-development-a-vaccine-for-acne.html#VRoBMbqL6QY|magazine=[[New Scientist]]|access-date=30 March 2015|url-status=live|archive-url=https://web.archive.org/web/20150402105716/http://www.newscientist.com/article/dn20958-in-development-a-vaccine-for-acne.html#VRoBMbqL6QY|archive-date=2 April 2015}}</ref> ==Other animals== Acne can [[Feline acne|occur on cats]],<ref>{{cite journal |last1=White |first1=Stephen D. |last2=Bordeau |first2=Patrick B. |last3=Blumstein |first3=Philippe |last4=Ibisch |first4=Catherine |last5=GuaguEre |first5=Eric |last6=Denerolle |first6=Philippe |last7=Carlotti |first7=Didier N. |last8=Scott |first8=Katherine V. |title=Feline acne and results of treatment with mupirocin in an open clinical trial: 25 cases (1994-96) |journal=Veterinary Dermatology |date=September 1997 |volume=8 |issue=3 |pages=157–164 |doi=10.1046/j.1365-3164.1997.d01-16.x |pmid=34644839 }}</ref> dogs,<ref>{{cite book|url=https://books.google.com/books?id=GvciAQAAIAAJ&pg=PA824|title=Veterinary Medicine|date=1914 |url-status=live|archive-url=https://web.archive.org/web/20170312122829/https://books.google.com/books?id=GvciAQAAIAAJ&lpg=PA824|archive-date=12 March 2017}}</ref> and horses.<ref>{{cite book|url=https://books.google.com/books?id=JP7TBQAAQBAJ&pg=PT3539|title=Veterinary Medicine: A textbook of the diseases of cattle, horses, sheep, pigs and goats|last1=Radostits|first1=Otto M.|last2=Gay|first2=Clive C.|last3=Hinchcliff|first3=Kenneth W.|last4=Constable|first4=Peter D. |date=28 December 2006|publisher=Elsevier Health Sciences|isbn=9780702039911 |url-status=live|archive-url=https://web.archive.org/web/20170312124704/https://books.google.com/books?id=JP7TBQAAQBAJ&lpg=PT3539|archive-date=12 March 2017}}</ref><ref>{{cite book|url=https://archive.org/details/cu31924000009260|page=[https://archive.org/details/cu31924000009260/page/n259 258]|title=A Text-book of the Principles and Practice of Veterinary Medicine|last=White|first=David Stuart |publisher=Lea & Febiger|date=1917 }}</ref> == References == {{Reflist}} == Further reading == {{Refbegin}} * {{cite book | first1 = Amy S. | last1 = Paller | first2 = Anthony J. | last2 = Mancini |title=Hurwitz's Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood And Adolescence |publisher=Elsevier |year=2015 |isbn=978-0-323-24475-6 }} * {{cite journal | vauthors = Cordain L, Lindeberg S, Hurtado M, Hill K, Eaton SB, Brand-Miller J | title = Acne vulgaris: a disease of Western civilization | journal = Archives of Dermatology | volume = 138 | issue = 12 | pages = 1584–90 | date = December 2002 | pmid = 12472346 | doi = 10.1001/archderm.138.12.1584 | doi-access = }} * {{cite journal | vauthors = Del Rosso JQ | title = The role of skin care as an integral component in the management of acne vulgaris: part 1: the importance of cleanser and moisturizer ingredients, design, and product selection | journal = The Journal of Clinical and Aesthetic Dermatology | volume = 6 | issue = 12 | pages = 19–27 | date = December 2013 | pmid = 24765221 | pmc = 3997205 }} * {{cite web | url = https://medlineplus.gov/acne.html | publisher = U.S. National Library of Medicine | department = [[MedlinePlus]] | title = Acne | access-date = 20 May 2020 | archive-date = 29 July 2020 | archive-url = https://web.archive.org/web/20200729021012/https://medlineplus.gov/acne.html | url-status = live }} {{Refend}} == External links == {{Commons category}} * [https://www.acnesupport.org.uk/ Acne Support]. Expert, impartial advice on acne by the [[British Association of Dermatologists]] (BAD). {{Medical condition classification and resources | DiseasesDB = 10765 | ICD10 = {{ICD10|L|70|0|l|60}} | ICD9 = {{ICD9|706.1}} | eMedicineSubj = derm | eMedicineTopic = 2 | MedlinePlus = 000873 | MeshID = D000152 }} {{Acne Agents}} {{Diseases of the skin and appendages by morphology}} {{Disorders of skin appendages}} {{Authority control}} {{DEFAULTSORT:Acne vulgaris}} [[Category:Acneiform eruptions]] [[Category:Cutaneous conditions]] [[Category:Puberty]] [[Category:Wikipedia emergency medicine articles ready to translate]] [[Category:Wikipedia medicine articles ready to translate]] [[Category:Greek inventions]]
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