Acne: Difference between revisions

Acne
Acne
Other names	Acne vulgaris
	Acne vulgaris in an 18-year-old male during puberty
Specialty	Dermatology
Symptoms	Blackheads, whiteheads, pimples, oily skin, scarring
Complications	Anxiety, reduced self-esteem, depression, thoughts of suicide
Usual onset	Puberty
Risk factors	Genetics
Differential diagnosis	Folliculitis, rosacea, hidradenitis suppurativa, miliaria
Treatment	Lifestyle changes, medications, medical procedures
Medication	Azelaic acid, benzoyl peroxide, salicylic acid, antibiotics, birth control pills, co-cyprindiol, retinoids, isotretinoin
Frequency	633 million affected (2015)

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Acne (/ˈækni/ ACK-nee) also known as acne vulgaris, is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles.^[10] Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and possible scarring.^[1]^[2]^[11] It primarily affects skin with a relatively high number of oil glands, including the face, upper part of the chest, and back.^[12] The resulting appearance can lead to lack of confidence, anxiety, reduced self-esteem, and, in extreme cases, depression or thoughts of suicide.^[3]^[4]

Susceptibility to acne is primarily genetic in 80% of cases.^[2] The roles of diet and cigarette smoking in the condition are unclear, and neither cleanliness nor exposure to sunlight are associated with acne.^[2]^[13]^[14] In both sexes, hormones called androgens appear to be part of the underlying mechanism, by causing increased production of sebum.^[5] Another common factor is the excessive growth of the bacterium Cutibacterium acnes, which is present on the skin.^[15]

Treatments for acne are available, including lifestyle changes, medications, and medical procedures. Eating fewer simple carbohydrates such as sugar may minimize the condition.^[7] Treatments applied directly to the affected skin, such as azelaic acid, benzoyl peroxide, and salicylic acid, are commonly used.^[8] Antibiotics and retinoids are available in formulations that are applied to the skin and taken by mouth for the treatment of acne.^[8] However, resistance to antibiotics may develop as a result of antibiotic therapy.^[16] Several types of birth control pills help prevent acne in women.^[8] Medical professionals typically reserve isotretinoin pills for severe acne, due to greater potential side effects.^[8]^[17] Early and aggressive treatment of acne is advocated by some in the medical community to decrease the overall long-term impact on individuals.^[4]

In 2015, acne affected approximately 633 million people globally, making it the eighth-most common disease worldwide.^[9]^[18] Acne commonly occurs in adolescence and affects an estimated 80–90% of teenagers in the Western world.^[19]^[20]^[21] Some rural societies report lower rates of acne than industrialized ones.^[21]^[22] Children and adults may also be affected before and after puberty.^[23] 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.^[2]

Classification

The severity of acne vulgaris (Gr. ἀκμή, "point" + L. vulgaris, "common")^[24] can be classified as mild, moderate, or severe to determine an appropriate treatment regimen.^[20] There is no universally accepted scale for grading acne severity.^[15] The presence of clogged skin follicles (known as comedones) limited to the face with occasional inflammatory lesions defines mild acne.^[20] Moderate severity acne is said to occur when a higher number of inflammatory papules and pustules occur on the face, compared to mild cases of acne, and appear on the trunk of the body.^[20] Severe acne is said to occur when nodules (the painful 'bumps' lying under the skin) are the characteristic facial lesions, and involvement of the trunk is extensive.^[20]^[25]

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.^[26]

Large nodules were previously called cysts. The term nodulocystic has been used in the medical literature to describe severe cases of inflammatory acne.^[25] True cysts are rare in those with acne, and the term severe nodular acne is now the preferred terminology.^[25]

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.^[27]^[28]^[29] 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.^[27]

Signs and symptoms

A photograph of a human face with nodular acne

A severe case of nodular acne

A photograph of a human back with nodular acne

Nodular acne on the back

A typical case of a teenager with acne, pimples in various parts of the head

Typical features of acne include increased secretion of oily sebum by the skin, microcomedones, comedones, papules, nodules (large papules), pustules, and often results in scarring.^[30]^[31] The appearance of acne varies with skin color. It may result in psychological and social problems.^[20]

Scars

Acne scars are caused by inflammation within the dermis and are estimated to affect 95% of people with acne vulgaris.^[32] Abnormal healing and dermal inflammation create the scar.^[33] Scarring is most likely to take place with severe acne but may occur with any form of acne vulgaris.^[32] 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.^[34]

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).^[33]^[34] Ice-pick scars, boxcar scars, and rolling scars are subtypes of atrophic acne scars.^[32] Boxcar scars are round or ovoid indented scars with sharp borders and vary in size from 1.5–4 mm across.^[33] Ice-pick scars are narrow (less than 2 mm across), deep scars that extend into the dermis.^[33] 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.^[33]

Hypertrophic scars are uncommon and are characterized by increased collagen content after the abnormal healing response.^[33] They are described as firm and raised from the skin.^[33]^[35] Hypertrophic scars remain within the original margins of the wound, whereas keloid scars can form scar tissue outside of these borders.^[33] Keloid scars from acne occur more often in men and people with darker skin, and usually occur on the trunk of the body.^[33]

In November 2021 a study^[36] was published exposing the consensus of twenty-four renowned international plastic surgeons and dermatologists about the most effective energy-based devices for the treatment of acne scars.^[37]

Pigmentation

After an inflamed nodular acne lesion resolves, it is common for the skin to darken in that area, which is known as postinflammatory hyperpigmentation (PIH). The inflammation stimulates specialized pigment-producing skin cells (known as melanocytes) to produce more melanin pigment, which leads to the skin's darkened appearance.^[38] PIH occurs more frequently in people with darker skin color.^[39] 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.^[40] Even minimal skin exposure to the sun's ultraviolet rays can sustain hyperpigmentation.^[38] Daily use of SPF 15 or higher sunscreen can minimize such a risk.^[40] Whitening agents like azelaic acid, arbutin or else may be used to improve hyperpigmentation.^[41]

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.^[2]^[42]^[43] Cleanliness (hygiene) and sunlight are not associated with acne.^[14]

Genes

Acne appears to be highly heritable; genetics explain 81% of the variation in the population.^[15] Studies performed in affected twins and first-degree relatives further demonstrate the strongly inherited nature of acne.^[2]^[15] Acne susceptibility is likely due to the influence of multiple genes, as the disease does not follow a classic (Mendelian) inheritance pattern. These gene candidates include certain variations in tumor necrosis factor-alpha (TNF-alpha), IL-1 alpha, and CYP1A1 genes, among others.^[19] The 308 G/A single nucleotide polymorphism variation in the gene for TNF is associated with an increased risk for acne.^[44] Acne can be a feature of rare genetic disorders such as Apert's syndrome.^[15] Severe acne may be associated with XYY syndrome.^[45]

Hormones

Hormonal activity, such as occurs during menstrual cycles and puberty, may contribute to the formation of acne. During puberty, an increase in sex hormones called androgens causes the skin follicle glands to grow larger and make more oily sebum.^[12] 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.^[46] 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).^[47]^[48]

Medical conditions that commonly cause a high-androgen state, such as polycystic ovary syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors, can cause acne in affected individuals.^[49]^[50] Conversely, people who lack androgenic hormones or are insensitive to the effects of androgens rarely have acne.^[49] Pregnancy can increase androgen levels, and consequently, oily sebum synthesis.^[50]^[51] Acne can be a side effect of testosterone replacement therapy or anabolic steroid use.^[1]^[52] Over-the-counter bodybuilding and dietary supplements often contain illegally added anabolic steroids.^[1]^[53]

Infections

The anaerobic bacterial species Cutibacterium acnes (formerly Propionibacterium acnes) contributes to the development of acne, but its exact role is not well understood.^[2] There are specific sub-strains of C. acnes associated with normal skin and others with moderate or severe inflammatory acne.^[54] 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.^[31]^[55] It is unclear whether eradication of the mite improves acne.^[55]

Diet

High-glycemic-load diets have been found to have different degrees of effect on acne severity.^[7]^[56]^[57] Multiple randomized controlled trials and nonrandomized studies have found a lower-glycemic-load diet to be effective in reducing acne.^[56] There is weak observational evidence suggesting that dairy milk consumption is positively associated with a higher frequency and severity of acne.^[55]^[56]^[58]^[59]^[60] Milk contains whey protein and hormones such as bovine IGF-1 and precursors of dihydrotestosterone.^[56] 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.^[56] Available evidence does not support a link between eating chocolate or salt and acne severity.^[58]^[59] Few studies have examined the relationship between obesity and acne.^[2] Vitamin B₁₂ may trigger skin outbreaks similar to acne (acneiform eruptions), or worsen existing acne when taken in doses exceeding the recommended daily intake.^[61]

Stress

There are few high-quality studies to demonstrate that stress causes or worsens acne.^[62] 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.^[63]^[64]

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.^[65] 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, hydantoin, isoniazid, glucocorticoids, iodides, bromides, and testosterone.^[45] When acne medicamentosa is specifically caused by 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 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. 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.^[66]

Pathophysiology

Simplistic representation of the formation of acne comedones

Acne vulgaris is a chronic skin disease of the pilosebaceous unit and develops due to blockages in the skin's hair follicles.^[54]

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.^[26] 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.^[26]

The blockages in the skin's hair follicles that cause acne vulgaris manifestations occur as a result of the following four abnormal processes: increased oily sebum production (influenced by androgens), 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.^[54]

The earliest pathologic change is the formation of a plug (a microcomedone), which is driven primarily by excessive growth, reproduction, and accumulation of skin cells in the hair follicle.^[1] In healthy skin, the skin cells that have died come up to the surface and exit the pore of the hair follicle.^[10] In people with acne, the increased production of oily sebum causes the dead skin cells to stick together.^[10] The accumulation of dead skin cell debris and oily sebum blocks the pore of the hair follicle, thus forming the microcomedone.^[10] The C. acnes biofilm within the hair follicle worsens this process.^[49] 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).^[1]^[10]^[20] In contrast, if the microcomedone occurs deep within the hair follicle, this causes the formation of a whitehead (known as a closed comedo).^[1]^[10]

The main hormonal driver of oily sebum production in the skin is dihydrotestosterone.^[1] Another androgenic hormone responsible for increased sebaceous gland activity is DHEA-S. The adrenal glands 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.^[10] C. acnes triggers skin inflammation in acne by increasing the production of several pro-inflammatory chemical signals (such as IL-1α, IL-8, TNF-α, and LTB4); IL-1α is essential to comedo formation.^[49]

C. acnes' ability to bind and activate a class of immune system receptors known as toll-like receptors (TLRs), especially TLR2 and TLR4, is a core mechanism of acne-related skin inflammation.^[49]^[67]^[68] Activation of TLR2 and TLR4 by C. acnes leads to increased secretion of IL-1α, IL-8, and TNF-α.^[49] The release of these inflammatory signals attracts various immune cells to the hair follicle, including neutrophils, macrophages, and Th1 cells.^[49] IL-1α stimulates increased skin cell activity and reproduction, which, in turn, fuels comedo development.^[49] Furthermore, sebaceous gland cells produce more antimicrobial peptides, such as HBD1 and HBD2, in response to the binding of TLR2 and TLR4.^[49]

C. acnes also provokes skin inflammation by altering the fatty composition of oily sebum.^[49] 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.^[49] Additionally, squalene oxidation increases 5-lipoxygenase enzyme activity, which catalyzes the conversion of arachidonic acid to leukotriene B4 (LTB4).^[49] LTB4 promotes skin inflammation by acting on the peroxisome proliferator-activated receptor alpha (PPARα) protein.^[49] PPARα increases the activity of activator protein 1 (AP-1) and NF-κB, thereby leading to the recruitment of inflammatory T cells.^[49] C. acnes' ability to convert sebum triglycerides to pro-inflammatory free fatty acids via secretion of the enzyme lipase further explains its inflammatory properties.^[49] These free fatty acids spur increased production of cathelicidin, HBD1, and HBD2, thus leading to further inflammation.^[49]

This inflammatory cascade typically leads to the formation of inflammatory acne lesions, including papules, infected pustules, or nodules.^[1] 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.^[1]^[69]^[70] The involvement of AP-1 in the aforementioned inflammatory cascade activates matrix metalloproteinases, which contribute to local tissue destruction and scar formation.^[49]

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 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.^[71]

Diagnosis

Acne vulgaris is diagnosed based on a medical professional's clinical judgment.^[15] 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.^[15] 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.^[29] Microcomedones (the precursor to blackheads and whiteheads) are not visible to the naked eye when inspecting the skin and require a microscope to be seen.^[29] 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.^[1]

Several scales exist to grade the severity of acne vulgaris, but disagreement persists about the ideal one for diagnostic use.^[72]^[73] 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.^[73] 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.^[73]^[74] The Pillsbury acne grading scale classifies the severity of the acne from grade 1 (least severe) to grade 4 (most severe).^[72]^[75]

Differential diagnosis

Many skin conditions can mimic acne vulgaris, and these are collectively known as acneiform eruptions.^[29] Such conditions include angiofibromas, epidermal cysts, flat warts, folliculitis, keratosis pilaris, milia, perioral dermatitis, and rosacea, among others.^[20]^[76] 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.^[20] Facial redness triggered by heat or the consumption of alcohol or spicy food is also more suggestive of rosacea.^[77] The presence of comedones helps health professionals differentiate acne from skin disorders that are similar in appearance.^[8] Chloracne and occupational acne due to exposure to certain chemicals & industrial compounds, may look very similar to acne vulgaris.^[78]

Management

Many different treatments exist for acne. These include alpha hydroxy acid, anti-androgen medications, antibiotics, antiseborrheic medications, azelaic acid, benzoyl peroxide, hormonal treatments, keratolytic soaps, nicotinamide, retinoids, and salicylic acid.^[79] 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.^[15] Typical treatments include topical therapies such as antibiotics, benzoyl peroxide, and retinoids, and systemic therapies, including antibiotics, hormonal agents, and oral retinoids.^[20]^[80]

Recommended therapies for first-line use in acne vulgaris treatment include topical retinoids, benzoyl peroxide, and topical or oral antibiotics.^[81] Procedures such as light therapy and laser therapy are not first-line treatments and typically have only an add on role due to their high cost and limited evidence.^[80] Blue light therapy is of unclear benefit.^[82] 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.^[15]

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.^[83]^[84]

Skin care

In general, it is recommended that people with acne do not wash affected skin more than twice daily.^[15] 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.^[15] Dermatologists recommend using cosmetic products that specifically say non-comedogenic, oil-free, and will not clog pores.^[15]

Acne vulgaris patients, even those with oily skin,^[85] should moisturize in order to support the skin's moisture barrier since skin barrier dysfunction may contribute to acne.^[85] 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.^[85] 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.^[86] 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.^[87]^[88]^[89]^[90]^[91]

Diet

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.^[92] Dermatologists also recommend a diet low in simple sugars as a method of improving acne.^[56] As of 2014, the available evidence is insufficient to use milk restriction for this purpose.^[56]

Medications

Benzoyl peroxide

Benzoyl peroxide (BPO) is a first-line treatment for mild and moderate acne due to its effectiveness and mild side-effects (mainly skin irritation). In the skin follicle, benzoyl peroxide kills C. acnes by oxidizing its proteins through the formation of oxygen free radicals and benzoic acid. These free radicals likely interfere with the bacterium's metabolism and ability to make proteins.^[93]^[94] Additionally, benzoyl peroxide is mildly effective at breaking down comedones and inhibiting inflammation.^[81]^[94] Combination products use benzoyl peroxide with a topical antibiotic or retinoid, such as benzoyl peroxide/clindamycin and benzoyl peroxide/adapalene, respectively.^[39] Topical benzoyl peroxide is effective at treating acne.^[95]

Side effects include increased skin photosensitivity, dryness, redness, and occasional peeling.^[96] 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.^[94]^[97] Unlike antibiotics, benzoyl peroxide does not appear to generate bacterial antibiotic resistance.^[96]

Retinoids

Retinoids are medications that reduce inflammation, normalize the follicle cell life cycle, and reduce sebum production.^[49]^[98] They are structurally related to vitamin A.^[98] Studies show dermatologists and primary care doctors underprescribe them for acne.^[15] The retinoids appear to influence the cell life cycle in the follicle lining. This helps prevent the accumulation of skin cells within the hair follicle that can create a blockage. They are a first-line acne treatment,^[1] especially for people with dark-colored skin. Retinoids are known to lead to faster improvement of postinflammatory hyperpigmentation.^[39]

Topical retinoids include adapalene, retinol, retinaldehyde, isotretinoin, tazarotene, trifarotene, and tretinoin.^[51]^[99]^[100] They often cause an initial flare-up of acne and facial flushing and can cause significant skin irritation. Generally speaking, retinoids increase the skin's sensitivity to sunlight and are therefore recommended for use at night.^[1] 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.^[1]^[101] Most formulations of tretinoin are incompatible for use with benzoyl peroxide.^[15] Tazarotene is the most effective and expensive topical retinoid but is usually not as well tolerated.^[1]^[101] In 2019 a tazarotene lotion formulation, marketed to be a less irritating option, was approved by the FDA.^[102] 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.^[1]^[20] 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.^[1] After a single round of treatment, about 80% of people report an improvement, with more than 50% reporting complete remission.^[20] About 20% of people require a second course, but 80% of those report improvement, resulting in a cumulative 96% efficacy rate.^[20]

There are concerns that isotretinoin is linked to adverse effects, like depression, suicidality, and anemia. There is no clear evidence to support some of these claims.^[1]^[20] Isotretinoin has been found in some studies to be superior to antibiotics or placebo in reducing acne lesions.^[17] However, a 2018 review comparing inflammatory lesions after treatment with antibiotics or isotretinoin found no difference.^[103] The frequency of adverse events was about twice as high with isotretinoin use, although these were mostly dryness-related events.^[17] No increased risk of suicide or depression was conclusively found.^[17]

Medical authorities strictly regulate isotretinoin use in women of childbearing age due to its known harmful effects in pregnancy.^[20] 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 birth control.^[20] In 2008, the United States started the iPLEDGE program to prevent isotretinoin use during pregnancy.^[104] 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.^[104] The effectiveness of the iPledge program is controversial due to continued instances of contraception nonadherence.^[104]^[105]

Antibiotics

People may apply antibiotics to the skin or take them orally to treat acne. They work by killing C. acnes and reducing inflammation.^[20]^[96]^[106] Although multiple guidelines call for healthcare providers to reduce the rates of prescribed oral antibiotics, many providers do not follow this guidance.^[107] Oral antibiotics remain the most commonly prescribed systemic therapy for acne.^[107] 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).^[16]^[96]^[106]^[107] Therefore, dermatologists prefer antibiotics as part of combination therapy and not for use alone.^[15]

Commonly used antibiotics, either applied to the skin or taken orally, include clindamycin, erythromycin, metronidazole, sulfacetamide, and tetracyclines (e.g., doxycycline or minocycline).^[51] Doxycycline 40 milligrams daily (low-dose) appears to have similar efficacy to 100 milligrams daily and has fewer gastrointestinal side effects.^[15] However, low-dose doxycycline is not FDA-approved for the treatment of acne.^[108] Antibiotics applied to the skin are typically used for mild to moderately severe acne.^[20] Oral antibiotics are generally more effective than topical antibiotics and produce faster resolution of inflammatory acne lesions than topical applications.^[1] The Global Alliance to Improve Outcomes in Acne recommends that topical and oral antibiotics are not used together.^[106]

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.^[106] 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.^[106]

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.^[1]^[15] Topical dapsone is sometimes a preferred therapy in women or for people with sensitive or darker-toned skin.^[15] It is not recommended for use with benzoyl peroxide due to the risk of causing yellow-orange skin discoloration with this combination.^[10] 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.^[109]

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.^[110]^[111]^[112] It is a narrow-spectrum tetracycline antibiotic that exhibits the necessary antibacterial activity against pathogens related to acne vulgaris and a low propensity for inducing antibiotic resistance.^[113]^[114] In clinical trials, sarecycline demonstrated clinical efficacy in reducing inflammatory acne lesions as early as three weeks and reduced truncal (back and chest) acne.^[112]^[115]

Hormonal agents

In women, the use of combined birth control pills can improve acne.^[116] These medications contain an estrogen and a progestin.^[117] 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.^[10]^[118] First-generation progestins such as norethindrone and norgestrel have androgenic properties and may worsen acne.^[15] Although oral estrogens decrease IGF-1 levels in some situations, which could theoretically improve acne symptoms,^[119]^[120] combined birth control pills do not appear to affect IGF-1 levels in fertile women.^[117]^[121] Cyproterone acetate-containing birth control pills seem to decrease total and free IGF-1 levels.^[122] Combinations containing third- or fourth-generation progestins, 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.^[123]^[124]^[125] Studies have shown a 40 to 70% reduction in acne lesions with combined birth control pills.^[118] A 2014 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.^[126] However, the two therapies are approximately equal in efficacy at six months for decreasing the number of inflammatory, non-inflammatory, and total acne lesions.^[126] 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.^[126] In contrast to combined birth control pills, progestogen-only birth control forms that contain androgenic progestins have been associated with worsened acne.^[107]

Antiandrogens such as cyproterone acetate and spironolactone can successfully treat acne, especially in women with signs of excessive androgen production, such as increased hairiness or skin production of sebum, or scalp hair loss.^[10]^[51] Spironolactone is an effective treatment for acne in adult women.^[127]^[128] Unlike combined birth control pills, it is not approved by the United States Food and Drug Administration for this purpose.^[1]^[39]^[127] Spironolactone is an aldosterone antagonist and is a useful acne treatment due to its ability to additionally block the androgen receptor at higher doses.^[39]^[107] Alone or in combination with a birth control pill, spironolactone has shown a 33 to 85% reduction in acne lesions in women.^[118] The effectiveness of spironolactone for acne appears to be dose-dependent.^[118] High-dose cyproterone acetate alone reportedly decreases acne symptoms in women by 75 to 90% within three months.^[129] It is usually combined with an estrogen to avoid menstrual irregularities and estrogen deficiency.^[130] 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%.^[131]^[132] 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.^[131]^[132]^[133]

Pregnant and lactating women should not receive antiandrogens for their acne due to a possibility of birth disorders such as hypospadias and feminization of male babies.^[51] 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.^[134] Antiandrogens are often combined with birth control pills for this reason, which can result in additive efficacy.^[39]^[135] The FDA added a 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.^[81]^[107]^[136] However, several large epidemiological studies subsequently found no greater risk of tumors in association with spironolactone in humans.^[107]^[137]^[138]^[139] Conversely, strong associations of cyproterone acetate with certain brain tumors have been discovered and its use has been restricted.^[140]^[141]^[142] The brain tumor risk with cyproterone acetate is due to its strong progestogenic actions and is not related to antiandrogenic activity nor shared by other antiandrogens.^[140]^[143]^[142]

Flutamide, a pure antagonist of the androgen receptor, is effective in treating acne in women.^[129]^[144] It appears to reduce acne symptoms by 80 to 90% even at low doses, with several studies showing complete acne clearance.^[129]^[145]^[146] In one study, flutamide decreased acne scores by 80% within three months, whereas spironolactone decreased symptoms by only 40% in the same period.^[146]^[147]^[148] In a large long-term study, 97% of women reported satisfaction with the control of their acne with flutamide.^[149] 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.^[150] As such, the use of flutamide for acne has become increasingly limited,^[149]^[151]^[152] and it has been argued that continued use of flutamide for such purposes is unethical.^[150] 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.^[134]^[153]^[154]^[155]

Clascoterone is a 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.^[156]^[157]^[158]^[159]^[160] It has shown no systemic absorption or associated antiandrogenic side effects.^[159]^[160]^[161] In a small direct head-to-head comparison, clascoterone showed greater effectiveness than topical isotretinoin.^[159]^[160]^[161] 5α-Reductase inhibitors 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.^[1]^[162]^[163]^[164] Moreover, 5α-reductase inhibitors have a strong potential for producing birth defects in male babies and this limits their use in women.^[1]^[163] However, 5α-reductase inhibitors are frequently used to treat excessive facial/body hair in women and can be combined with birth control pills to prevent pregnancy.^[162] There is no evidence as of 2010 to support the use of cimetidine or ketoconazole in the treatment of acne.^[165]

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.^[165] Hormone therapy is effective for acne both in women with hyperandrogenism and in women with normal androgen levels.^[165]

Azelaic acid

Azelaic acid is effective for mild to moderate acne when applied topically at a 15–20% concentration.^[69]^[166]^[167]^[168] Treatment twice daily for six months is necessary, and is as effective as topical benzoyl peroxide 5%, isotretinoin 0.05%, and erythromycin 2%.^[169] Azelaic acid is an effective acne treatment due to its ability to reduce skin cell accumulation in the follicle and its antibacterial and anti-inflammatory properties.^[69] 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.^[1] Azelaic acid may cause skin irritation.^[170] It is less effective and more expensive than retinoids.^[1] 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.^[171]

Salicylic acid

Salicylic acid is a topically applied beta-hydroxy acid that stops bacteria from reproducing and has keratolytic properties.^[172]^[173] It is less effective than retinoid therapy.^[20] Salicylic acid opens obstructed skin pores and promotes the shedding of epithelial skin cells.^[172] Dry skin is the most commonly seen side effect with topical application, though darkening of the skin can occur in individuals with darker skin types.^[1]

Other medications

Topical and oral preparations of nicotinamide (the amide form of vitamin B₃) are alternative medical treatments.^[174] Nicotinamide reportedly improves acne due to its anti-inflammatory properties, its ability to suppress sebum production, and its wound healing properties.^[174] Topical and oral preparations of zinc are suggested treatments for acne; evidence to support their use for this purpose is limited.^[175] Zinc's capacities to reduce inflammation and sebum production as well as inhibit C. acnes growth are its proposed mechanisms for improving acne.^[175] Antihistamines may improve symptoms among those already taking isotretinoin due to their anti-inflammatory properties and their ability to suppress sebum production.^[176]

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.^[38] By interfering with the production of melanin in the epidermis, hydroquinone leads to less hyperpigmentation as darkened skin cells are naturally shed over time.^[38] 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.^[38] The use of a sunscreen with SPF 15 or higher in the morning with reapplication every two hours is recommended when using hydroquinone.^[38] 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.^[38] 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.^[38] Most preparations contain the preservative sodium metabisulfite, which has been linked to rare cases of allergic reactions, including anaphylaxis and severe asthma exacerbations in susceptible people.^[38] 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).^[38]

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.^[10]^[51] The use of topical benzoyl peroxide and antibiotics together is more effective than antibiotics alone.^[10] Similarly, using a topical retinoid with an antibiotic clears acne lesions faster than the use of antibiotics alone.^[10] Frequently used combinations include the following: antibiotic and benzoyl peroxide, antibiotic and topical retinoid, or topical retinoid and benzoyl peroxide.^[51] 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.^[10]

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.^[177] 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.^[177] Highly recommended therapies include topically applied benzoyl peroxide (pregnancy category C) and azelaic acid (category B).^[177] 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 too little amniotic fluid in the uterus and early closure of the babies' ductus arteriosus blood vessel.^[51]^[177] Prolonged use of salicylic acid over significant areas of the skin or under occlusive (sealed) dressings is not recommended as these methods increase systemic absorption and the potential for fetal harm.^[177] Tretinoin (category C) and adapalene (category C) are very poorly absorbed, but certain studies have suggested teratogenic effects in the first trimester.^[177] The data examining the association between maternal topical retinoid exposure in the first trimester of pregnancy and adverse pregnancy outcomes is limited.^[178] A systematic review of observational studies concluded that such exposure does not appear to increase the risk of major birth defects, miscarriages, stillbirths, premature births, or low birth weight.^[178] Similarly, in studies examining the effects of topical retinoids during pregnancy, fetal harm has not been seen in the second and third trimesters.^[177] Nevertheless, since rare harms from topical retinoids are not ruled out, they are not recommended for use during pregnancy due to persistent safety concerns.^[178]^[179] Retinoids contraindicated for use during pregnancy include the topical retinoid tazarotene, and oral retinoids isotretinoin and acitretin (all category X).^[177] Spironolactone is relatively contraindicated for use during pregnancy due to its antiandrogen effects.^[1] Finasteride is not recommended as it is highly teratogenic.^[1]

Topical antibiotics deemed safe during pregnancy include clindamycin, erythromycin, and metronidazole (all category B), due to negligible systemic absorption.^[51]^[177] Nadifloxacin and dapsone (category C) are other topical antibiotics that may be used to treat acne in pregnant women but have received less study.^[51]^[177] No adverse fetal events have been reported from the topical use of dapsone.^[177] 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.^[20] Oral antibiotics deemed safe for pregnancy (all category B) include azithromycin, cephalosporins, and penicillins.^[177] Tetracyclines (category D) are contraindicated during pregnancy as they are known to deposit in developing fetal teeth, resulting in yellow discoloration and thinned tooth enamel.^[1]^[177] Their use during pregnancy has been associated with the development of acute fatty liver of pregnancy and is further avoided for this reason.^[177]

Procedures

Limited evidence supports comedo extraction, but it is an option for comedones that do not improve with standard treatment.^[8]^[81] Another procedure for immediate relief is the injection of a corticosteroid into an inflamed acne comedo.^[81] Electrocautery and electrofulguration are effective alternative treatments for comedones.^[180]

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.^[8]^[181] 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;^[182] it may have a role for individuals whose acne has been resistant to topical medications.^[10] A 2016 meta-analysis was unable to conclude whether light therapies were more beneficial than placebo or no treatment, nor the duration of benefit.^[183]

When regular light is used immediately following the application of a sensitizing substance to the skin such as aminolevulinic acid or methyl aminolevulinate, the treatment is referred to as photodynamic therapy (PDT).^[107]^[166] PDT has the most supporting evidence of all light therapy modalities.^[81] PDT treats acne by using various forms of light (e.g., blue light or red light) that preferentially target the pilosebaceous unit.^[107] 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.^[107] 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 CO₂ 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.^[184] 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.^[8]^[185]^[186] 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.^[166] 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.^[10] Typical side effects include skin peeling, temporary reddening of the skin, swelling, and post-inflammatory hyperpigmentation.^[10]

Dermabrasion is an effective therapeutic procedure for reducing the appearance of superficial atrophic scars of the boxcar and rolling varieties.^[33] Ice-pick scars do not respond well to treatment with dermabrasion due to their depth.^[33] The procedure is painful and has many potential side effects such as skin sensitivity to sunlight, redness, and decreased pigmentation of the skin.^[33] Dermabrasion has fallen out of favor with the introduction of laser resurfacing.^[33] Unlike dermabrasion, there is no evidence that microdermabrasion is an effective treatment for acne.^[8]

Dermal or subcutaneous fillers 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.^[187] Examples of fillers used for this purpose include hyaluronic acid; poly(methyl methacrylate) microspheres with collagen; human and bovine collagen derivatives, and fat harvested from the person's own body (autologous fat transfer).^[187]

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.^[184] 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.^[184]^[188]

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.^[189]^[190]^[191]

Chemical peels can be used to reduce the appearance of acne scars.^[33] 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 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.^[33] Higher concentrations of trichloroacetic acid (30–40%) are considered to be medium-strength peels and affect the skin as deep as the papillary dermis.^[33] Formulations of trichloroacetic acid concentrated to 50% or more are considered to be deep chemical peels.^[33] 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 small white superficial cysts known as milia.^[33]

Alternative medicine

Researchers are investigating complementary therapies as treatment for people with acne.^[192] 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.^[192] Tea tree oil appears to be approximately as effective as benzoyl peroxide or salicylic acid but is associated with allergic contact dermatitis.^[1] Proposed mechanisms for tea tree oil's anti-acne effects include antibacterial action against C. acnes and anti-inflammatory properties.^[68] Numerous other plant-derived therapies have demonstrated positive effects against acne (e.g., basil oil; oligosaccharides from seaweed; however, few well-done studies have examined their use for this purpose.^[193] There is a lack of high-quality evidence for the use of acupuncture, herbal medicine, or cupping therapy for acne.^[192]

Self-care

Many over-the-counter treatments in many forms are available, which are often known as cosmeceuticals.^[194] Certain types of makeup may be useful to mask acne.^[195] In those with oily skin, a water-based product is often preferred.^[195]^[196]

Prognosis

Acne usually improves around the age of 20 but may persist into adulthood.^[79] Permanent physical scarring may occur.^[20] Rare complications from acne or its treatment include the formation of pyogenic granulomas, osteoma cutis, and acne with facial edema.^[197] Early and aggressive treatment of acne is advocated by some in the medical community to reduce the chances of these poor outcomes.^[4]

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, and suicidal thoughts.^[3]^[32]^[55]^[83]

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.^[198]^[83] Such blame can worsen the affected person's sense of self-esteem.^[198] Until the 20th century, even among dermatologists, the list of causes was believed to include excessive sexual thoughts and masturbation.^[199] Dermatology's association with sexually transmitted infections, especially syphilis, contributed to the stigma.^[199]

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.^[63]^[200] 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.^[63]

Epidemiology

Globally, acne affects approximately 650 million people, or about 9.4% of the population, as of 2010.^[201] It affects nearly 90% of people in Western societies during their teenage years, but can occur before adolescence and may persist into adulthood.^[19]^[20]^[23] 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^[51]^[202] and has a lifetime prevalence of 85%.^[51] About 20% of those affected have moderate or severe cases.^[2] It is slightly more common in females than males (9.8% versus 9.0%).^[201] In those over 40 years old, 1% of males and 5% of females still have problems.^[20]

Rates appear to be lower in rural societies.^[22] While some research has found it affects people of all ethnic groups,^[203] acne may not occur in the non-Westernized peoples of Papua New Guinea and Paraguay.^[204]

Acne affects 40–50 million people in the United States (16%) and approximately 3–5 million in Australia (23%).^[126]^[205] Severe acne tends to be more common in people of Caucasian or Amerindian descent than in people of African descent.^[21]

History

Domolene ointment, a mid-1900s medication that was claimed to cure acne

Historical records indicate Pharaohs 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).^[206] The sixth-century Greek physician Aëtius of Amida reportedly coined the term "ionthos" (ίονθωξ,) or "acnae", which seems to be a reference to facial skin lesions that occur during "the 'acme' of life" (puberty).^[207]

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 tubercles that altered a person's facial appearance during adolescence and were neither itchy nor painful.^[207]

The recognition and characterization of acne progressed in 1776 when Josef Plenck (an Austrian physician) published a book that proposed the novel concept of classifying skin diseases by their elementary (initial) lesions.^[207] In 1808 the 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.^[207] 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.^[207] Erasmus Wilson, in 1842, was the first to make the distinction between acne vulgaris and rosacea.^[208] The first professional medical monograph dedicated entirely to acne was written by Lucius Duncan Bulkley and published in New York in 1885.^[199]^[209]

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.^[207] 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.^[207] 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.^[207]

The approach to acne treatment underwent significant changes during the twentieth century. Retinoids became a medical treatment for acne in 1943.^[98] Benzoyl peroxide was first proposed as a treatment in 1958 and remains a staple of acne treatment.^[210] 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.^[207] Subsequently, in the 1970s, tretinoin (original trade name Retin A) was found to be an effective treatment.^[211] The development of oral isotretinoin (sold as Accutane and Roaccutane) followed in 1980.^[212] After its introduction in the United States, 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.^[213]^[214]

Treatment of acne with topical crushed dry ice, known as cryoslush, was first described in 1907 but is no longer performed commonly.^[215] Before 1960, the use of X-rays was also a common treatment.^[216]^[217]

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 doctor visits and costs over US$2.5 billion each year in direct costs.^[13] Similarly, acne vulgaris is responsible for 3.5 million doctor visits each year in the United Kingdom.^[20] Sales for the top ten leading acne treatment brands in the US in 2015 amounted to $352 million.^[218]

Acne vulgaris and its resultant scars are associated with significant social and academic difficulties that can last into adulthood.^[32]^[219] During the Great Depression, dermatologists discovered that young men with acne had difficulty obtaining jobs.^[199] 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.^[199] During World War II, some soldiers in tropical climates developed such severe and widespread tropical acne on their bodies that they were declared medically unfit for duty.^[199]

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).^[10] 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.^[10]^[107] 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.^[107] 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.^[10]

The use of antimicrobial peptides against C. acnes is under investigation as a treatment for acne to overcoming antibiotic resistance.^[10] In 2007, scientists reported the first genome sequencing of a C. acnes bacteriophage (PA6). The authors proposed applying this research toward the development of bacteriophage therapy as an acne treatment to overcome the problems associated with long-term antibiotic use, such as bacterial resistance.^[220] Oral and topical probiotics are under evaluation as treatments for acne.^[221] 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.^[221] As of 2014, knowledge of the effects of probiotics on acne in humans was limited.^[221]

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.^[10] A vaccine against inflammatory acne has shown promising results in mice and humans.^[54]^[222] 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.^[223]

Other animals

Acne can occur on cats,^[224] dogs,^[225] and horses.^[226]^[227]

References

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External links

Acne Support. Expert, impartial advice on acne by the British Association of Dermatologists (BAD).

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@@ Line 19: / Line 19: @@
 | risks         = [[Genetics]]<ref name="Bhate2013" />
 | diagnosis     =
-| differential  = [[Folliculitis]], [[rosacea]], [[hidradenitis suppurativa]], [[miliaria]]<ref>{{cite book |last1=Kahan |first1=Scott | name-list-style = vanc |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>
+| 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" />
@@ Line 28: / Line 28: @@
 }}
-'''Acne''', 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 }}{{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 }}</ref>
+'''Acne''' ([[Help:IPA/English|/ˈækni/]] ''[[Help:Pronunciation respelling key|ACK-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 appear to play a part.<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"/>
+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 }}</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 }}</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/>
+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 = 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/>
@@ Line 38: / Line 38: @@
 ==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 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/>
@@ Line 58: / Line 60: @@
 | 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 }}</ref><ref name=Zhao2012/> The appearance of acne varies with skin color. It may result in psychological and social problems.<ref name=BMJ2013/>
+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===
@@ Line 67: / Line 69: @@
 [[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/>
-In November 2021 a study<ref>{{Cite journal|title=Energy-based devices for the treatment of acne scars: 2021 international consensus recommendations|year=2021|doi=10.1002/lsm.23484|last1=Salameh|first1=Fares|last2=Shumaker|first2=Peter R.|last3=Goodman|first3=Greg J.|last4=Spring|first4=Leah K.|last5=Seago|first5=Meghan|last6=Alam|first6=Murad|last7=Al-Niaimi|first7=Firas|last8=Cassuto|first8=Daniel|last9=Chan|first9=Henry HL|last10=Dierickx|first10=Christine|last11=Donelan|first11=Matthias|last12=Gauglitz|first12=Gerd G.|last13=Haedersdal|first13=Merete|last14=Krakowski|first14=Andrew C.|last15=Manuskiatti|first15=Woraphong|last16=Norbury|first16=William B.|last17=Ogawa|first17=Rei|last18=Ozog|first18=David M.|last19=Paasch|first19=Uwe|last20=Victor Ross|first20=E.|last21=Clementoni|first21=Matteo Tretti|last22=Waibel|first22=Jill|last23=Bayat|first23=Ardeshir|last24=Goo|first24=Boncheol Leo|last25=Artzi|first25=Ofir|journal=Lasers in Surgery and Medicine|volume=54|issue=1|pages=10–26|pmid=34719045|s2cid=240355253|doi-access=}}</ref> was published exposing the consensus of twenty-four renowned international plastic surgeons and dermatologists about the most effective energy-based devices for the treatment of acne scars.<ref>{{Cite web|title=International Consensus Recommend Acne Scar Treatments|url=https://www.dermatologytimes.com/view/international-consensus-recommend-acne-scar-treatments|access-date=2021-11-28|website=Dermatology Times|date=24 November 2021 }}</ref>
+In November 2021 a study<ref>{{cite journal|title=Energy-based devices for the treatment of acne scars: 2021 international consensus recommendations|year=2021|doi=10.1002/lsm.23484|last1=Salameh|first1=Fares|last2=Shumaker|first2=Peter R.|last3=Goodman|first3=Greg J.|last4=Spring|first4=Leah K.|last5=Seago|first5=Meghan|last6=Alam|first6=Murad|last7=Al-Niaimi|first7=Firas|last8=Cassuto|first8=Daniel|last9=Chan|first9=Henry HL|last10=Dierickx|first10=Christine|last11=Donelan|first11=Matthias|last12=Gauglitz|first12=Gerd G.|last13=Haedersdal|first13=Merete|last14=Krakowski|first14=Andrew C.|last15=Manuskiatti|first15=Woraphong|last16=Norbury|first16=William B.|last17=Ogawa|first17=Rei|last18=Ozog|first18=David M.|last19=Paasch|first19=Uwe|last20=Victor Ross|first20=E.|last21=Clementoni|first21=Matteo Tretti|last22=Waibel|first22=Jill|last23=Bayat|first23=Ardeshir|last24=Goo|first24=Boncheol Leo|last25=Artzi|first25=Ofir|journal=Lasers in Surgery and Medicine|volume=54|issue=1|pages=10–26|pmid=34719045|s2cid=240355253|doi-access=}}</ref> was published exposing the consensus of twenty-four renowned international plastic surgeons and dermatologists about the most effective energy-based devices for the treatment of acne scars.<ref>{{cite web|title=International Consensus Recommend Acne Scar Treatments|url=https://www.dermatologytimes.com/view/international-consensus-recommend-acne-scar-treatments|access-date=2021-11-28|website=Dermatology Times|date=24 November 2021|archive-date=28 November 2021|archive-url=https://web.archive.org/web/20211128091810/https://www.dermatologytimes.com/view/international-consensus-recommend-acne-scar-treatments|url-status=live}}</ref>
 ===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]]&nbsp;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>
+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]]&nbsp;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/ }}</ref> Sunlight and cleanliness are not associated with acne.<ref name="Schnopp2011"/>
+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]]; genetics explain 81% of the variation in the population.<ref name="Zaenglein2018"/> Studies performed in affected [[twin studies|twins]] and [[first-degree relatives]] further demonstrate the strongly inherited nature of acne.<ref name="Bhate2013"/><ref name="Zaenglein2018"/> Acne susceptibility is likely due to the influence of multiple genes, as the disease does not follow a classic [[Mendelian inheritance|(Mendelian)]] inheritance pattern. These gene candidates include [[Polymorphism (biology)|certain variations]] in [[TNF-alpha|tumor necrosis factor-alpha (TNF-alpha)]], [[IL-1 alpha]], and [[CYP1A1]] genes, among others.<ref name="Taylor2011"/> The 308&nbsp;G/A [[single nucleotide polymorphism]] variation in the gene for [[Tumor necrosis factors|TNF]] is associated with an increased risk for acne.<ref name=Yang2014>{{cite journal | vauthors = Yang JK, Wu WJ, Qi J, He L, Zhang YP | title = TNF-308 G/A polymorphism and risk of acne vulgaris: a meta-analysis | journal = PLOS ONE | volume = 9 | issue = 2 | pages = e87806 | date = February 2014 | pmid = 24498378 | pmc = 3912133 | doi = 10.1371/journal.pone.0087806 | type = Systematic Review & Meta-Analysis | bibcode = 2014PLoSO...987806Y | doi-access = free }}</ref> Acne can be a feature of rare genetic disorders such as [[Apert's syndrome]].<ref name="Zaenglein2018">{{cite journal | vauthors = Zaenglein AL | title = Acne Vulgaris | journal = The New England Journal of Medicine | volume = 379 | issue = 14 | pages = 1343–1352 | date = October 2018 | pmid = 30281982 | doi = 10.1056/NEJMcp1702493 | s2cid = 52914179 | type = Review }}</ref> Severe acne may be associated with [[XYY syndrome]].<ref name="FitzAtlas">{{cite book| vauthors = Fitzpatrick TB |title=Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology|date=2005|publisher=McGraw-Hill Medical Pub. Division|location=New York|isbn=978-0071440196|page=2|edition=5th}}</ref>
+Acne appears to be highly [[Heritability|heritable]]; [[Gene|genetics]] explain 81% of the variation in the population.<ref name="Zaenglein2018"/> Studies performed in affected [[twin studies|twins]] and [[first-degree relatives]] further demonstrate the strongly inherited nature of acne.<ref name="Bhate2013"/><ref name="Zaenglein2018"/> Acne susceptibility is likely due to the influence of multiple genes, as the disease does not follow a classic [[Mendelian inheritance|(Mendelian)]] inheritance pattern. These gene candidates include [[Polymorphism (biology)|certain variations]] in [[TNF-alpha|tumor necrosis factor-alpha (TNF-alpha)]], [[IL-1 alpha]], and [[CYP1A1]] genes, among others.<ref name="Taylor2011"/> The 308&nbsp;G/A [[single nucleotide polymorphism]] variation in the gene for [[Tumor necrosis factors|TNF]] is associated with an increased risk for acne.<ref name=Yang2014>{{cite journal | vauthors = Yang JK, Wu WJ, Qi J, He L, Zhang YP | title = TNF-308 G/A polymorphism and risk of acne vulgaris: a meta-analysis | journal = PLOS ONE | volume = 9 | issue = 2 | pages = e87806 | date = February 2014 | pmid = 24498378 | pmc = 3912133 | doi = 10.1371/journal.pone.0087806 | type = Systematic Review & Meta-Analysis | bibcode = 2014PLoSO...987806Y | doi-access = free }}</ref> Acne can be a feature of rare genetic disorders such as [[Apert's syndrome]].<ref name="Zaenglein2018">{{cite journal | vauthors = Zaenglein AL | title = Acne Vulgaris | journal = The New England Journal of Medicine | volume = 379 | issue = 14 | pages = 1343–1352 | date = October 2018 | pmid = 30281982 | doi = 10.1056/NEJMcp1702493 | s2cid = 52914179 | type = Review }}</ref> Severe acne may be associated with [[XYY syndrome]].<ref name="FitzAtlas">{{cite book| vauthors = Fitzpatrick TB |title=Fitzpatrick's Color Atlas and Synopsis of Clinical Dermatology|date=2005|publisher=McGraw-Hill Medical Pub. Division|location=New York|isbn=978-0071440196|page=2|edition=5th}}</ref>
 ===Hormones===
@@ Line 90: / Line 92: @@
 === 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 }}</ref>
+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, when acne is caused by mechanical obstruction it is not considered a form of acne vulgaris when being very technical, and would be an other [[acneiform eruption]] known as [[Acne mechanica]].
+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]].
@@ Line 104: / Line 106: @@
 [[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/>
-Acne vulgaris is a chronic skin disease of the [[pilosebaceous unit]] and develops due to blockages in the skin's [[hair follicle]]s. These blockages 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>
+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 |issue= |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"/>
@@ Line 114: / Line 120: @@
 ''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. | name-list-style = vanc |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/>
+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>
@@ Line 124: / Line 130: @@
 ===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 }}</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>
+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==
@@ Line 131: / Line 137: @@
 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 }}</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>
+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/ }}</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>
+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=www.healio.com}}</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/>
+[[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=www.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===
@@ Line 153: / Line 159: @@
 [[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 }}</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}}</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.
+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&nbsp;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" />
@@ Line 164: / Line 170: @@
 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|name-list-style=vanc|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" />
+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" />
@@ Line 170: / Line 176: @@
 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 journal |title=Prescribing Information for Seysara|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209521s007lbl.pdf}}</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 }}</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 }}</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 }}</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 }}</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 }}</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=BMJ |volume=381 |language=en |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>
+[[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=BMJ |volume=381 |language=en |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}}</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 = BMJ | volume = 372 | issue = | pages = n37 | date = February 2021 | pmid = 33536184 | doi = 10.1136/bmj.n37 | url = | 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 }}</ref><ref name="pmid33536184" />
+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 = BMJ | volume = 372 | issue = | pages = n37 | date = February 2021 | pmid = 33536184 | doi = 10.1136/bmj.n37 | url = | 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 | name-list-style = vanc |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}}</ref><ref name="BalenFranks2010">{{cite book| first1 = Adam | last1 = Balen | first2 = Stephen | last2 = Franks | first3 = Roy | last3 = Homburg | first4 = Sean | last4 = Kehoe | name-list-style = vanc |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–}}</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 }}</ref>
+[[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 }}</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}}</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| name-list-style = vanc  | 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 }}</ref><ref name="Danby2015">{{cite book| first = F. William | last = Danby | name-list-style = vanc |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–}}</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>
+[[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" />
@@ Line 187: / Line 193: @@
 ====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&nbsp;5%, isotretinoin&nbsp;0.05%, and erythromycin&nbsp;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>
+[[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&nbsp;5%, isotretinoin&nbsp;0.05%, and erythromycin&nbsp;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====
@@ Line 226: / Line 232: @@
 ===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 | name-list-style = vanc |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>
+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 | name-list-style = vanc |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"/>
+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}}</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" />
+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" />
@@ Line 252: / Line 258: @@
 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 | name-list-style = vanc |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|name-list-style=vanc|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>
+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" />
@@ Line 273: / Line 279: @@
 ==Other animals==
-Acne can occur on [[Feline acne|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. | name-list-style = vanc |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 | name-list-style = vanc |publisher=Lea & Febiger|date=1917 }}</ref>
+Acne can occur on [[Feline acne|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 ==
@@ Line 280: / Line 286: @@
 == Further reading ==
 {{Refbegin}}
-* {{cite book | first1 = Amy S. | last1 = Paller | first2 = Anthony J. | last2 = Mancini  | name-list-style = vanc |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 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 }}
+* {{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}}
@@ Line 307: / Line 313: @@
 [[Category:Acneiform eruptions]]
 [[Category:Cutaneous conditions]]
-[[Category:Dermatology task force articles]]
 [[Category:Puberty]]
 [[Category:Wikipedia emergency medicine articles ready to translate]]

Classification	D ICD-10: L70.0 ICD-9-CM: 706.1 MeSH: D000152 DiseasesDB: 10765
External resources	MedlinePlus: 000873 eMedicine: derm/2 Patient UK: Acne

v t e Acne-treating agents (D10)
Antibacterial	Azelaic acid Benzoyl peroxide^# 8-Hydroxyquinoline Blue light therapy Tea tree oil
Keratolytic	Glycolic acid Salicylic acid^# Sulfur Benzoyl peroxide^#
Anti-inflammatory	Niacinamide Ibuprofen^# Aspirin^# Red light therapy
Antibiotics	Clindamycin Dapsone Erythromycin Sulfacetamide Tetracyclines (Lymecycline Minocycline Doxycycline)
Hormonal	Antiandrogens Bicalutamide Cyproterone acetate Drospirenone Flutamide Spironolactone) Estrogens Estradiol Ethinylestradiol
Retinoids	Adapalene Isotretinoin Motretinide Tazarotene Tretinoin Trifarotene
Other	Epristeride Mesulfen Pelretin Stridex Tioxolone
Combinations	Adapalene/benzoyl peroxide Clindamycin/adapalene/benzoyl peroxide Clindamycin/benzoyl peroxide Clindamycin/tretinoin Erythromycin/benzoyl peroxide Erythromycin/isotretinoin Sulfacetamide/sulfur Tretinoin/benzoyl peroxide
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III

Authority control databases
International	FAST
National	Germany United States France BnF data Japan Czech Republic 2 Israel