Acne vulgaris

Acne vulgaris
Classification and external resources
Acne of a 14-year-old male during puberty
ICD- 10	L 70.0
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. 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. 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. For most people, acne diminishes over time and tends to disappear — or at the very least decreases — by age 25. 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.

Some of the large nodules were previously called " cysts" and the term nodulocystic has been used to describe severe cases of inflammatory acne. 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. Cystic acne affects deeper skin tissue than does common acne.

Aside from scarring, its main effects are psychological, such as reduced self-esteem and in very extreme cases, depression or suicide. 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.

Terminology

The term acne comes from a mutation of the Greek ἀκμή (akmē), literally "point, edge", but in the sense of a "skin eruption" in the writings of Aëtius Amidenus. Used by itself, the term "acne" refers to the presence of pustules and papules. 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.

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. Chloracne is associated with exposure to polyhalogenated compounds.

Signs and symptoms

Typical features of acne include: seborrhea (increased oil-sebum secretion), comedones (blackheads and whiteheads), papules (pinheads), pustules ( pimples), nodules (large papules) and, possibly scarring. The appearance of acne varies with skin colour.

Scars

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.

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

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

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  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

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.

Hormonal

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. Use of anabolic steroids may have a similar effect. 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

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.

Psychological

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

Infectious

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. 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 either 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. In vitro, resistance of P. acnes to commonly used antibiotics has been increasing, as well.

Diet

A high glycemic load diet is associated with worsening acne. There is also a positive association between the consumption of milk and a greater rate and severity of acne. Other associations such as chocolate and salt are not supported by the evidence. However, chocolate contains a varying amount of sugar that can lead to a high glycemic load, and it can be made with or without milk in one form or another (see types of chocolate).

Diagnosis

There are multiple grading scales for grading the severity of acne vulgaris, 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

• Keratosis pilaris
• Rosacea
• Chloracne

Management

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. 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.

Medications

Benzoyl peroxide

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. 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. Unlike antibiotics, benzoyl peroxide does not appear to generate bacterial resistance.

Antiseptics

Sometimes benzoyl peroxide topical medication is combined with a salt of hydroxyquinoline, such as potassium hydroxyquinoline sulphate, which has antibacterial properties. One such topical product is available without prescription in the UK.

Antibiotics

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

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 (Retin-A), adapalene (Differin), and tazarotene (Tazorac). 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. Effective topical retinoids have been in use for over 30 years, but are available only on prescription, so are not as widely used as the other topical treatments. Topical retinoids often cause an initial flare-up of acne and facial flushing.

Oral retinoids

A daily oral intake of vitamin A derivative isotretinoin (marketed as Roaccutane, Accutane, Amnesteem, Sotret, Claravis, Clarus) over a period of 4–6 months can cause long-term resolution or reduction of acne. It is believed that isotretinoin works primarily by reducing the secretion of oils from the glands, but some studies suggest that it affects other acne-related factors as well. Isotretinoin has been shown to be very effective in treating severe acne and can either improve or clear well over 80% of patients. The drug has a much longer effect than antibacterial treatments and will often cure acne for good. The treatment requires close medical supervision by a dermatologist because the drug has many known side effects (many of which can be severe). About 25% of patients relapse after one treatment. In those cases, a second treatment for another 4–6 months may be indicated to obtain desired results. It is often recommended that one let a few months pass between the two treatments, because the condition can actually improve somewhat in the time after stopping the treatment and waiting a few months also gives the body a chance to recover. On occasion, a third or even a fourth course is used, but the benefits are often less substantial. The most common side effects are dry skin and occasional nosebleeds (secondary to dry nasal mucosa). Oral retinoids also often cause an initial flare-up of acne within a month or so, which can be severe. There are reports that the drug has damaged the liver of patients. For this reason, it is recommended that patients have blood samples taken and examined before and during treatment. In some cases, treatment is terminated or reduced due to elevated liver enzymes in the blood, which might be related to liver damage. Others claim that the reports of permanent damage to the liver are unsubstantiated, and routine testing is considered unnecessary by some dermatologists. Blood triglycerides also need to be monitored. However, routine testing is part of the official guidelines for the use of the drug in many countries. Some press reports suggest that isotretinoin may cause depression, but, as of September 2005, there is no agreement in the medical literature as to the risk. The drug also causes birth defects if women become pregnant while taking it or take it while pregnant. For this reason, female patients are required to use two separate forms of birth control or vow abstinence while on the drug. Because of this, the drug is supposed to be given to females as a last resort after milder treatments have proven insufficient. Restrictive rules (see iPledge program) for use were put into force in the USA beginning in March 2006 to prevent misuse, causing occasioned widespread editorial comment.

Anti-inflammatories

Nicotinamide, (vitamin B₃) used topically in the form of a gel, has been shown in a 1995 study to be of comparable efficacy to topical clindamycin used for comparison. The benefit of topical nicotinamide seems to lie in its anti-inflammatory nature. It is also purported to result in increased synthesis of collagen, keratin, involucrin and flaggrin. According to a cosmetic company, it may be useful for reducing skin hyperpigmentation (dark acne marks), increasing skin moisture and reducing fine wrinkles.

Ibuprofen is used in combination with tetracycline for some moderate acne cases.

Mandelic acid has been noted to be an effective topical treatment for mild to moderate acne. It is considered to be a gentler alternative to popular alpha hydroxy acids such as glycolic acid and lactic acid.

Procedures

Comedo extraction

Comedones (whiteheads or blackheads) do not improve with standard topical, antibiotic or hormonal therapy. These small plugs must be physically removed with the use of comedo extraction. An extractor, which has a metal loop at one end or a spoon with a central hole, to place around the comedone and squeeze out its contents with firm pressure to the skin. This is easiest for blackheads, which already have an opening to the skin surface, however to extract whiteheads a sharp needle is needed to firstly incise the overlying skin before squeezing out the contents of the comedone. If performed by an experienced professional this technique should not cause scarring. Following extraction the regular use of a topical retinoid may then prevent a recurrence.

Dermabrasion

Dermabrasion is a cosmetic medical procedure in which the surface of the skin is removed by abrasion (sanding). It is used to remove sun-damaged skin and to remove or lessen scars and dark spots on the skin. The procedure is very painful and usually requires a general anaesthetic or "twilight anaesthesia", in which the patient is still partly conscious. Afterward, the skin is very red and raw-looking, and it takes several months for the skin to regrow and heal. Dermabrasion is useful for scar removal when the scar is raised above the surrounding skin, but is less effective with sunken scars.

In the past, dermabrasion was done using a small, sterilized, electric sander. In the past decade, it has become more common to use laser dermabrasion using CO₂, Er:YAG laser or a combination of both for the treatment of acne scars. Indications for CO₂ laser treatment include previous non erythematous and non-proliferative hypertrophic scars, atrophic acne scars and burn scars. Laser dermabrasion is much easier to control, much easier to gauge, and is practically bloodless compared to classic dermabrasion.

Phototherapy

Blue and red light

Light exposure has long been used as a short-term treatment for acne. Recently, visible light has been successfully employed to treat mild to moderate acne ( phototherapy or deep penetrating light therapy) - in particular intense violet light (405–420 nm) generated by purpose-built fluorescent lighting, dichroic bulbs, LEDs or lasers. Used twice weekly, this has been shown to reduce the number of acne lesions by about 64% and is even more effective when applied daily. The mechanism appears to be that a porphyrin (Coproporphyrin III) produced within P. acnes generates free radicals when irradiated by 420 nm and shorter wavelengths of light. Particularly when applied over several days, these free radicals ultimately kill the bacteria. Since porphyrins are not otherwise present in skin, and no UV light is employed, it appears to be safe, and has been cleared for marketing by the U.S. FDA.

It seems that the treatment works even better if used with a mixture of the violet light and red visible light (660 nanometer), resulting in a 76% reduction of lesions after three months of daily treatment for 80% of the patients; and overall clearance was similar or better than benzoyl peroxide. Unlike most of the other treatments, few if any negative side-effects are typically experienced, and the development of bacterial resistance to the treatment seems very unlikely. After treatment, clearance can be longer-lived than is typical with topical or oral antibiotic treatments; several months is not uncommon. The equipment or treatment, however, is relatively new and reasonably expensive to buy initially, although the total cost of ownership can be similar to many other treatment methods (such as the total cost of benzoyl peroxide, moisturizer, washes) over a couple of years of use.

Photodynamic therapy

In addition, basic science and clinical work by dermatologists Yoram Harth and Alan Shalita and others have produced evidence that intense blue/violet light (405–425 nanometer) can decrease the number of inflammatory acne lesion by 60–70% in four weeks of therapy, in particular, when the P. acnes is pretreated with delta-aminolevulinic acid (ALA), which increases the production of porphyrins. However this photodynamic therapy is controversial and not published in a peer-reviewed journal. A phase II trial, while it showed improvement occurred, failed to show improved response compared to the blue/violet light alone.

Laser treatment

Laser surgery has been in use for some time to reduce the scars left behind by acne, but research has been done on lasers for prevention of acne formation itself. The laser is used to produce one of the following effects:

• to burn away the follicle sac from which the hair grows
• to burn away the sebaceous gland, which produces the oil
• to induce formation of oxygen in the bacteria, killing them

Since lasers and intense pulsed light sources cause thermal damage to the skin, there are concerns that laser or intense pulsed light treatments for acne will induce hyperpigmented macules (spots) or cause long-term dryness of the skin.

The FDA has approved the use of a cosmetic laser for the treatment of acne. However, efficacy studies have used very small sample sizes for periods of six months or less, and have shown contradictory results. Also, laser treatment being relatively new, protocols remain subject to experimentation and revision, and treatment can be quite expensive. Also, some Smoothbeam laser devices had to be recalled due to coolant failure, which resulted in painful burn injuries to patients.

Surgery

For people with cystic acne, boils can be drained through surgical lancing.

Natural medicine

Given the link between a high-glycemic diet and aggravation or induction of acne, 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. 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. 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%. Azelaic acid may cause skin irritation but is otherwise very safe.

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

Prognosis

Acne usually improves around the age of 20 but may persist into adulthood.

Epidemiology

Globally acne affects approximately 650 million people, or about 9.4% of the population, as of 2010. It affects slightly more females than males (9.8% versus 9.0%). Acne affects 40 to 50 million people in the United States (16%) and approximately 3 to 5 million in Australia (23%). It affects people of all ethnic groups.

History

• Ancient Egypt and Ancient Greece: Sulfur was used to treat acne.
• 1920s: Benzoyl peroxide was used as a medication to treat acne.
• 1970s: Tretinoin (original Trade Name Retin A) was found to be an effective treatment for acne. This preceded the development of oral isotretinoin (sold as Accutane and Roaccutane) in 1980. 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.

Research

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

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."