Acne vulgaris
Classification and external resources
Acne of a 14-year-old male during puberty
ICD-10	L70.0
ICD-9	706.1
DiseasesDB	10765
MedlinePlus	000873
eMedicine	derm/2
MeSH	D000152

Acne vulgaris (cystic acne or simply acne) is a common human skin disease, characterized by areas of skin with seborrhea (scaly red skin), comedones (blackheads and whiteheads), papules (pinheads), pustules (pimples), nodules (large papules) and possibly scarring.^[1] Acne affects mostly skin with the densest population of sebaceous follicles; these areas include the face, the upper part of the chest, and the back. Severe acne is inflammatory, but acne can also manifest in noninflammatory forms.^[2] The lesions are caused by changes in pilosebaceous units, skin structures consisting of a hair follicle and its associated sebaceous gland, changes that require androgen stimulation.

Acne occurs most commonly during adolescence, and often continues into adulthood. In adolescence, acne is usually caused by an increase in testosterone, which accrues during puberty, regardless of sex.^[3] For most people, acne diminishes over time and tends to disappear — or at the very least decreases — by age 25.^[4] There is, however, no way to predict how long it will take to disappear entirely, and some individuals will carry this condition well into their thirties, forties, and beyond.^[5]

Some of the large nodules were previously called "cysts" and the term nodulocystic has been used to describe severe cases of inflammatory acne.^[6] The "cysts", or boils that accompany cystic acne, can appear on the buttocks, groin, and armpit area, and anywhere else where sweat collects in hair follicles and perspiration ducts.^[7] Cystic acne affects deeper skin tissue than does common acne.^[8]

Aside from scarring, its main effects are psychological, such as reduced self-esteem^[9] and in very extreme cases, depression or suicide.^[10] Acne usually appears during adolescence, when people already tend to be most socially insecure. Early and aggressive treatment is therefore advocated by some to lessen the overall long-term impact to individuals.^[9]

Terminology [edit]

The term acne comes from a mutation of the Greek ἀκμή (akmē), literally "point, edge", but in the sense of a "skin eruption"^[11] in the writings of Aëtius Amidenus. Used by itself, the term "acne" refers to the presence of pustules and papules.^[12] The most common form of acne is known as acne vulgaris, meaning "common acne". Many teenagers get this type of acne. Use of the term "acne vulgaris" implies the presence of comedones.^[13]

The term "acne rosacea" is a synonym for rosacea, however some individuals may have almost no acne comedones associated with their rosacea and therefore prefer the term rosacea.^[14] Chloracne is associated with exposure to polyhalogenated compounds.

Signs and symptoms [edit]

Typical features of acne include: seborrhea (increased oil-sebum secretion), comedones (blackheads and whiteheads), papules (pinheads), pustules (pimples), nodules (large papules) and, possibly scarring.^[1] The appearance of acne varies with skin color. It may result in psychological and social problems.^[15]

Scars [edit]

Acne scars are the result of inflammation within the dermis brought on by acne. The scar is created by the wound trying to heal itself resulting in too much collagen in one spot.^[16]

Physical acne scars are often referred to as "ice pick" scars. This is because the scars tend to cause an indentation in the skin's surface. There is a range of treatments available. Although quite rare, the medical condition atrophia maculosa varioliformis cutis also results in "acne-like" depressed scars on the face.

• Ice pick scars: Deep pits, that are the most common and a classic sign of acne scarring.
• Box car scars: Angular scars that usually occur on the temple and cheeks, and can be either superficial or deep, these are similar to chickenpox scars.
• Rolling scars: Scars that give the skin a wave-like appearance.
• Hypertrophic scars: Thickened, or keloid scars.

Pigmentation [edit]

Pigmented scars is a slightly misleading term, as it suggests a change in the skin's pigmentation and that they are true scars; however, neither is true. Pigmented scars are usually the result of nodular or cystic acne (the painful 'bumps' lying under the skin). They often leave behind an inflamed red mark. Often, the pigmentation scars can be avoided simply by avoiding aggravation of the nodule or cyst. Pigmentation scars nearly always fade with time taking between three months to two years to do so, although can last indefinitely if untreated.

• 

  A severe case of cystic acne

• 

  Cystic acne on the back.

• 

  Different types of Acne Vulgaris: A: Cystic acne on the face, B: Subsiding tropical acne of trunk, C: Extensive acne on chest and shoulders.

Cause [edit]

Acne develops as a result of blockages in the follicles. Hyperkeratinization and formation of a plug of keratin and sebum (a microcomedo) is the earliest change. Enlargement of sebaceous glands and an increase in sebum production occur with increased androgen (DHEA-S) production at adrenarche. The microcomedo may enlarge to form an open comedone (blackhead) or closed comedone (milia). Comedones are the direct result of sebaceous glands' becoming clogged with sebum, a naturally occurring oil, and dead skin cells. In these conditions, the naturally occurring largely commensal bacterium Propionibacterium acnes can cause inflammation, leading to inflammatory lesions (papules, infected pustules, or nodules) in the dermis around the microcomedo or comedone, which results in redness and may result in scarring or hyperpigmentation.^[17]

Hormonal [edit]

Hormonal activity, such as menstrual cycles and puberty, may contribute to the formation of acne. During puberty, an increase in sex hormones called androgens cause the follicular glands to grow larger and make more sebum.^[18] Use of anabolic steroids may have a similar effect.^[19] Several hormones have been linked to acne: the androgens testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone sulfate (DHEAS), as well as insulin-like growth factor 1 (IGF-I).

Development of acne vulgaris in later years is uncommon, although the incidence of rosacea, which may have a similar presentation, is increased in older age groups. True acne vulgaris in adult women may be a feature of an underlying condition such as pregnancy, or disorders such as polycystic ovary syndrome and Cushing's syndrome. Menopause-associated acne (known as acne climacterica) occurs as production of the natural anti-acne ovarian hormones estradiol and progesterone fail, permitting the acnegenic hormone testosterone to exert its effects unopposed.

Genetic [edit]

The predisposition for specific individuals to acne is likely explained by a genetic component, which has been supported by twin studies as well as studies that have looked at rates of acne among first degree relatives. The genetics of acne susceptibility is likely polygenic, as the disease does not follow classic Mendelian inheritance pattern. There are multiple candidates for genes which are possibly related to acne, including polymorphisms in TNF-alpha, IL-1 alpha, CYP1A1 among others.^[20]

Psychological [edit]

While the connection between acne and stress has been debated, scientific research indicates that "increased acne severity" is "significantly associated with increased stress levels."^[21] The National Institutes of Health (USA) list stress as a factor that "can cause an acne flare."^[22] A study of adolescents in Singapore "observed a statistically significant positive correlation … between stress levels and severity of acne."^[23]

Infectious [edit]

Propionibacterium acnes (P. acnes) is the anaerobic bacterium species that is widely concluded to cause acne, though Staphylococcus epidermidis has been universally discovered to play some role since normal pores appear colonized only by P. acnes.^[24] Regardless, there are specific clonal sub-strains of P. acnes associated with normal skin health and others with long-term acne problems. It is as yet inconclusive whether any of these undesirable strains evolve on-site in the adverse conditions or are all pathogenically acquired, or possibly both depending on the individual patient. These strains either have the capability of changing, perpetuating, or adapting to, the abnormal cycle of inflammation, oil production, and inadequate sloughing activities of acne pores. At least one particularly virulent strain, though, has been circulating around Europe for at least 87 years.^[25] In vitro, resistance of P. acnes to commonly used antibiotics has been increasing, as well.^[26]

Diet [edit]

The relationship between diet and acne is not very clear as there is no good quality evidence.^[27] However, a high glycemic load diet is associated with worsening acne.^[28][29] There is also a positive association between the consumption of milk and a greater rate and severity of acne.^[30][28][31] Other associations such as chocolate and salt are not supported by the evidence.^[28] Chocolate however does contain a varying amount of sugar that can lead to a high glycemic load, and it can be made with or without milk. There may be a relationship between acne and insulin metabolism and a dated trial found a relationship between acne and obesity.^[32]

Diagnosis [edit]

There are multiple scales for grading the severity of acne vulgaris,^[33] three of these being:

• Leeds acne grading technique: Counts and categorises lesions into inflammatory and non-inflammatory (ranges from 0–10.0).
• Cook's acne grading scale: Uses photographs to grade severity from 0 to 8 (0 being the least severe and 8 being the most severe).
• Pillsbury scale: Simply classifies the severity of the acne from 1 (least severe) to 4 (most severe).

Differential [edit]

Other similar conditions include: rosacea, folliculitis, keratosis pilaris, perioral dermatitis, and angiofibromas among others.^[15]

Management [edit]

Many different treatments exist for acne including benzoyl peroxide, antibiotics, retinoids, antiseborrheic medications, anti-androgen medications, hormonal treatments, salicylic acid, alpha hydroxy acid, azelaic acid, nicotinamide, and keratolytic soaps.^[34] They are believed to work in at least 4 different ways, including: normalising shedding into the pore to prevent blockage, killing Propionibacterium acnes, anti-inflammatory effects, hormonal manipulation.^{[citation needed]}

Medications [edit]

Benzoyl peroxide

Benzoyl peroxide cream.

Benzoyl peroxide is a first-line treatment for mild and moderate acne vulgaris due to its effectiveness and mild side-effects (primarily an irritant dermatitis). It works against the "P. acnes" bacterium, and normally causes just dryness of the skin, slight redness, and occasional peeling when side effects occur.^[35] This topical does increase sensitivity to the sun as indicated on the package, so sunscreen should be used during the treatment to prevent sunburn. Benzoyl peroxide has been found to be nearly as effective as antibiotics with all concentrations 2.5%, 5.0%, and 10% equally effective.^[35] Unlike antibiotics, benzoyl peroxide does not appear to generate bacterial resistance.^[35]

Antibiotics

Antibiotics are reserved for more severe cases.^[35] With increasing resistance of P. acnes worldwide, they are becoming less effective.^[35] Commonly used antibiotics, either applied topically or taken orally, include erythromycin, clindamycin, and tetracyclines such as minocycline.

Sometimes benzoyl peroxide topical medication is combined with a salt of hydroxyquinoline, such as potassium hydroxyquinoline sulphate, which has antibacterial properties.

Hormones

In females, acne can be improved with hormonal treatments. The common combined estrogen/progestogen methods of hormonal contraception have some effect, but the antiandrogen cyproterone in combination with an oestrogen (Diane 35) is particularly effective at reducing androgenic hormone levels. Diane-35 is not available in the USA, but a newer oral contraceptive containing the progestin drospirenone is now available with fewer side effects than Diane 35 / Dianette. Both can be used where blood tests show abnormally high levels of androgens, but are effective even when this is not the case. Along with this, treatment with low-dose spironolactone can have anti-androgenetic properties, especially in patients with polycystic ovarian syndrome.

Topical retinoids

Topical retinoids are medications that normalize the follicle cell life cycle. This class includes tretinoin, adapalene, and tazarotene. Like isotretinoin, they are related to vitamin A, but they are administered topically and they generally have much milder side effects. They can, however, cause significant irritation of the skin. The retinoids appear to influence the cell life cycle in the follicle lining. This helps prevent the hyperkeratinization of these cells that can create a blockage. Retinol, a form of vitamin A, has similar, but milder, effects and is used in many over-the-counter moisturizers and other topical products. Topical retinoids often cause an initial flare-up of acne and facial flushing.

Oral retinoids

Isotretinoin is very effective for severe acne as well as moderate acne that does not improve with other treatments.^[15] Improvement is typically seen after one to two months of use. After a single course about 80% of people are improved with more than 50% completely so.^[15] About 20% of people require a second course.^[15] A number of adverse effects may occur including: dry skin, nose bleeds, muscle pains, increased liver enzymes, and increased lipid levels in the blood.^[15] If used during pregnancy there is a high risk of abnormalities in the baby and thus women of child bearing age are required to use effective birth control.^[15] Psychiatric side effects such as depression and suicide are unclear.^[15]

Procedures [edit]

Comedo extraction may help those with comedones that do not improve with standard treatment, at least temporarily.^[36] There is no evidence that mircrodermabrasion is effective.^[36]

Evidence for light therapy and lasers as of 2012 is not sufficient to recommend them.^[37] While light therapy appears to provide short term benefit, there is a lack of long term outcome data or data in those with severe acne.^[38]

Laser surgery can be used to reduce the scars left behind by acne.^[39]

For people with cystic acne, boils can be drained through surgical lancing.^[8]

Alternative medicine [edit]

Given the link between a high-glycemic diet and aggravation or induction of acne,^[29][40] avoidance of sugary foods is a mainstay of natural recommendations for prevention and treatment of acne. Larger, more rigorous trials are needed to definitely determine whether this approach is effective.

Numerous natural products have been investigated for treating patients with acne.^[41] Some of these, such as azelaic acid, are widely used in conventional medicine as well, highlighting that not all natural approaches should be labeled "alternative."

Azelaic acid, a naturally-occurring hydrocarbon found in whole grains among other sources, has been repeatedly shown effective for mild-to-moderate acne when applied topically at a 20% concentration.^[42] Application twice daily for six months is necessary, and treatment has been shown as effective as topical benzoyl peroxide 5%, tretinoin 5%, and erythromycin 2%.^[43] Azelaic acid may cause skin irritation but is otherwise very safe.

A topical application of tea tree oil (melaleuca steam-distilled essential oil) 5% was as effective as topical benzoyl peroxide 5% (though its effects came on more slowly) but without the excessive drying of the benzoyl peroxide and was significantly more effective than placebo with similar low risk of adverse effects.^[44][45] The mechanism of action of tea tree oil has not been determined, but it appears to be broadly antimicrobial, anti-inflammatory, and antioxidant.^[46]

Prognosis [edit]

Acne usually improves around the age of 20 but may persist into adulthood.^[34] Permanent scarring may occur.^[15]

Epidemiology [edit]

Globally acne affects approximately 650 million people, or about 9.4% of the population, as of 2010.^[47] It affects almost 90% of people during their teenage years and often persists into adulthood.^[15] It affects slightly more females than males (9.8% versus 9.0%).^[47] In those over 40 years old, 1% of males and 5% of females still have problems.^[15] Acne affects 40 to 50 million people in the United States (16%) and approximately 3 to 5 million in Australia (23%).^[48] It affects people of all ethnic groups.^[49]

History [edit]

• Ancient Egypt and Ancient Greece: Sulfur was used to treat acne.^{[citation needed]}
• 1920s: Benzoyl peroxide was used as a medication to treat acne.^{[citation needed]}
• 1970s: Tretinoin (original Trade Name Retin A) was found to be an effective treatment for acne.^[50] This preceded the development of oral isotretinoin (sold as Accutane and Roaccutane) in 1980.^[51] Also, antibiotics such as minocycline are used as treatments for acne.
• 1980s: Accutane is introduced in the United States, and later found to be a teratogen, highly likely to cause birth defects if taken during pregnancy. In the United States, more than 2,000 women became pregnant while taking the drug between 1982 and 2003, with most pregnancies ending in abortion or miscarriage. About 160 babies with birth defects were born.^[52][53]

Research [edit]

A vaccine against inflammatory acne has been tested successfully in mice, but it is not certain that it would work similarly in humans.^[54]

A 2007 microbiology article reporting the first genome sequencing of a Propionibacterium acnes bacteriophage (PA6) said this "should greatly enhance the development of a potential bacteriophage therapy to treat acne and, therefore, overcome the significant problems associated with long-term antibiotic therapy and bacterial resistance."^[55]

References [edit]

External links [edit]

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