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==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 = 357β64 | 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 = 545β553 | 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=18β26 |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=26β32 |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 β 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=261β267 |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=33β39 |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=296β302 |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=359β370 |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=1044β1052 |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 β some of them compelling β 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 = 1485β92 | 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 = 945β73.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 = 141β52 | 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 = 2555β62 | 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 = 275β7 | 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 = 265β76 | 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 = 7β16 | 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 = 323β9 | 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 4β6 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, LΓΊcio 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 = 175β84 | 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 = 290β3 | 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, DrΓ©no 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 = 538β549 | 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 = 333β338 | 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 = 1235β1242 | 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 = 987β996 | 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 = 1162β74 | 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 = 3β63 | 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 = 306β314 | 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=363β407 |isbn=978-3-642-64261-6 }}</ref><ref name="Kuhl1997">{{cite journal |last1=Kuhl |first1=H. |title=Metabolische Effekte der Γstrogene und Gestagene |journal=Der GynΓ€kologe |date=18 April 1997 |volume=30 |issue=4 |pages=357β369 |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 = 372β86 | 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 = 343β358 | date = April 2017 | pmid = 28292450 | doi = 10.1016/j.pcl.2016.11.005 | type = Review }}</ref><ref name="pmid29725277">{{cite journal | vauthors = SΕopieΕ R, Milewska E, Rynio P, MΔczekalski 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 = 1β4 | 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 = 450β9 | 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 = 169β191 | 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 = 623β9 | 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 = 6β37 | 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=179β188 |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 = 53β8 | 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 = 231β242 | 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 5Ξ±-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies | journal = Breast Cancer Res. Treat. | volume = 174 | issue = 1 | pages = 15β26 | 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 = 49β55 | 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 = 1008β1009 | 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=171β175 |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 = 184β188 | 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 GuΓ©rinel 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 = 95β101 | 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 = 37β46 | 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 = 166β72 | 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 = 455β465 | 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 = 707β23 | 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 = 132β | 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 = 44β52 | 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 = 69β77 | 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=Γzlem |last3=Bastu |first3=Ercan |last4=UΔurlucan |first4=Funda GΓΌngΓΆr |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=110β119 |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 = 168β172 | 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 = 1509β1521 | 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 = 96β104 | 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 = 37β48 | 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 = 68β73 | 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 = 1β9 | 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 = 797β809 | 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 = 505β516 | 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 = 56β71 | 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 = 91β101 | 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" /> [[5Ξ±-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 5Ξ±-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=147β|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 = 95β107 | date = March 2013 | pmid = 23431485 | doi = 10.1258/acb.2012.012159 | s2cid = 8325257 | doi-access = free }}</ref> Moreover, 5Ξ±-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, 5Ξ±-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 = 17β23 | 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 15β20% 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=841β847 |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=13β6 |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 = 285β96 | 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 = 22β31; 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 = 788β792 | 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 = 324β8 | 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 = 542β5 | 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 = 147β57 | 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 therapyβusing medications of different classes together, each with a different mechanism of actionβhas 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 = 112β8 | 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 (9β25%), 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 = 1132β41 | 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 = 351β8 | 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 = 597β598 | 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 = 1273β85 | 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 = 302β11 | 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 = 1160β9 | 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 = 348β55 | 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 = 1107β8 | 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-Γ -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=125β132 |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 = 276β81 | 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 = 1413β1419 | 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 (30β40%) 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 = 1137β52 | 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 = 32β40 | 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 = 1β6 | 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>
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