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Monday, February 8, 2010

Acne vulgaris

Acne vulgaris (commonly called acne) is a common human skin disease, characterized by areas of skin with multiple noninflammatory follicular papules or comedones and by inflammatory papules, pustules, and nodules in its more severe forms. Acne vulgaris mostly affects the areas of 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.[1] Acne lesions are commonly referred to as pimples, blemishes, spots, zits, or simply acne. Acne lesions are caused by changes in pilosebaceous units, skin structures consisting of a hair follicle and its associated sebaceous gland, changes which require androgen stimulation.

Acne occurs most commonly during adolescence, affecting more than 89% of teenagers, and frequently continues into adulthood. In adolescence, acne is usually caused by an increase in male sex hormones, which people of both genders accrue during puberty.[2] For most people, acne diminishes over time and tends to disappear—or at the very least decrease—after one reaches one's early twenties. 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.[3]

The face and upper neck are the most commonly affected, but the chest, back and shoulders may have acne as well. The upper arms can also have acne, but lesions found there are often keratosis pilaris, not acne. Typical acne lesions are comedones, inflammatory papules, pustules and nodules.

Some of the large nodules were previously called "cysts" and the term nodulocystic has been used to describe severe cases of inflammatory acne.[4] 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.[5] Cystic acne affects deeper skin tissue than does common acne.[6]

Aside from scarring, its main effects are psychological, such as reduced self-esteem[7] and, according to at least one study, depression or suicide.[8] 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 impact to individuals.[7]

Terminology


The term acne comes from a corruption of the Greek άκμή (acne 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.[9] 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.[10]

The term "acne rosacea" is a synonym for rosacea, however some individuals may have almost no acne comedones associated with their rosacea and prefer therefore the term rosacea.[11] Chloracne is associated with exposure to polyhalogenated compounds.

Causes of acne

Acne develops as a result of blockages in 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 (whitehead). Whiteheads 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 bacteria 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.[12]

Primary causes


Acne is known to be partly hereditary, but no particular genetic cause has been identified. Acne is not contagious or infectious. Several factors are known to be linked to acne:

  • Family/Genetic history. The tendency to develop acne runs in families. For example, school-age boys with acne often have other members in their family with acne as well. A family history of acne is associated with an earlier occurrence of acne and an increased number of retentional acne lesions.[13]
  • Hormonal activity, such as menstrual cycles and puberty. During puberty, an increase in male sex hormones called androgens cause the follicular glands to grow larger and make more sebum.[14]
  • Inflammation, skin irritation or scratching of any sort will activate inflammation.
  • Stress. While the connection between acne and stress has been debated, scientific research indicates that "increased acne severity" is "significantly associated with increased stress levels."[15] The National Institutes of Health (USA) list stress as a factor that "can cause an acne flare."[16] A study of adolescents in Singapore "observed a statistically significant positive correlation […] between stress levels and severity of acne."[17]
  • Hyperactive sebaceous glands, secondary to the three hormone sources above.
  • Bacteria in the pores. Propionibacterium acnes (P. acnes) is the anaerobic bacterium that causes acne. In-vitro resistance of P. acnes to commonly used antibiotics has been increasing.[18]
  • Use of anabolic steroids.[19]
  • Exposure to certain chemical compounds. Chloracne is particularly linked to toxic exposure to dioxins, namely Chlorinated dioxins.[citation needed]

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 this is the age group for Rosacea which may have similar appearances. True acne vulgaris in adult women may be a feature of an underlying condition such as pregnancy and disorders such as polycystic ovary syndrome or the rare Cushing's syndrome. Menopause-associated acne occurs as production of the natural anti-acne ovarian hormone estradiol fails at menopause. The lack of estradiol also causes thinning hair, hot flashes, thin skin, wrinkles, vaginal dryness, and predisposes to osteopenia and osteoporosis as well as triggering acne (known as acne climacterica in this situation).

Vitamins A and E

Studies have shown that newly diagnosed acne patients tend to have lower levels of vitamin A circulating in their bloodstream than those who are acne free.[44] In addition people with severe acne also tend to have lower blood levels of vitamin E.[45]

Hygiene

Acne is not caused by dirt. This misconception probably comes from the fact that blackheads look like dirt stuck in the openings of pores. The black color is not dirt but simply oxidized keratin. In fact, the blockages of keratin that cause acne occur deep within the narrow follicle channel, where it is impossible to wash them away. These plugs are formed by the failure of the cells lining the duct to separate and flow to the surface in the sebum created there by the body. Built-up oil of the skin can block the passages of these pores, so standard washing of the face could wash off old oil and help unblock the pores.

Treatments


Available treatments

There are many products available for the treatment of acne, many of which are without any scientifically proven effects. Generally speaking, successful treatments show little improvement within the first two weeks, instead taking a period of approximately three months to improve and start flattening out.[citation needed] Many treatments that promise big improvements within two weeks are likely to be largely disappointing.[citation needed] However, short bursts of cortisone can give very quick results, and other treatments can rapidly improve some active spots, but usually not all active spots.[citation needed]

Modes of improvement are not necessarily fully understood but in general treatments are believed to work in at least 4 different ways (with many of the best treatments providing multiple simultaneous effects):

  • normalising shedding into the pore to prevent blockage
  • killing Propionibacterium acnes
  • anti-inflammatory effects
  • hormonal manipulation

A combination of treatments can greatly reduce the amount and severity of acne in many cases. Those treatments that are most effective tend to have greater potential for side effects and need a greater degree of monitoring, so a step-wise approach is often taken. Many people consult with doctors when deciding which treatments to use, especially when considering using any treatments in combination. There are a number of treatments that have been proven effective:

Hygiene

Proper washing and skin care can help to remove bacteria and oils which cause acne. Some anecdotal reports indicate placing a clean towel over one's pillow each night can help prevent contaminating the pillow with the bacteria that causes acne, and reintroducing it to the face. Additionally, cleaning the hands before touching the affected area can prevent transmission of the bacteria from one part of the body to another.[citation needed]

Topical bactericidals

Widely available OTC bactericidal products containing benzoyl peroxide may be used in mild to moderate acne. The gel or cream containing benzoyl peroxide is applied, twice daily, into the pores over the affected region. Bar soaps or washes may also be used and vary from 2% to 10% in strength. In addition to its therapeutic effect as a keratolytic (a chemical that dissolves the keratin plugging the pores) benzoyl peroxide also prevents new lesions by killing P. acnes. In one study, roughly 70% of participants using a 10% benzoyl peroxide solution experienced a reduction in acne lesions after six weeks.[46] Unlike antibiotics, benzoyl peroxide has the advantage of being a strong oxidizer and thus does not appear to generate bacterial resistance.[47] However, it routinely causes dryness, local irritation and redness. A sensible regimen may include the daily use of low-concentration (2.5%) benzoyl peroxide preparations, combined with suitable non-comedogenic moisturisers to help avoid overdrying the skin.

Care must be taken when using benzoyl peroxide, as it can very easily bleach any fabric or hair it comes in contact with.

Other antibacterials that have been used include triclosan, or chlorhexidine gluconate. Though these treatments are often less effective, they also have fewer side-effects.

Products containing azeleic acid are also used in the treatment of P. acnes. It is available in the United States as a 20% concentration and does not generate bacterial resistance.[47]

Prescription-strength benzoyl peroxide preparations do not necessarily differ with regard to the maximum concentration of the active ingredient (10%), but the drug is made available dissolved in a vehicle that more deeply penetrates the pores of the skin.

Topical antibiotics

Externally applied antibiotics such as erythromycin, clindamycin or tetracycline kill the bacteria that are harbored in the blocked follicles. While topical use of antibiotics is equally as effective as oral use, this method avoids possible side effects including upset stomach and drug interactions (e.g. it will not affect use of the oral contraceptive pill), but may prove inefficient to apply over larger areas than just the face alone.

Oral antibiotics

Oral antibiotics used to treat acne include erythromycin or one of the tetracycline antibiotics (tetracycline, the better absorbed oxytetracycline, or one of the once daily doxycycline, minocycline, or lymecycline). Trimethoprim is also sometimes used (off-label use in UK). However, reducing the P. acnes bacteria will not, in itself, do anything to reduce the oil secretion and abnormal cell behaviour that is the initial cause of the blocked follicles. Additionally the antibiotics are becoming less and less useful as resistant P. acnes are becoming more common. Acne may return soon after the end of treatment—days later in the case of topical applications, and weeks later in the case of oral antibiotics. Furthermore, side effects of tetracycline antibiotics can include yellowing of the teeth and an imbalance of gut flora, so are only recommended after topical products have been ruled out.

It has been found that sub-antimicrobial doses of antibiotics such as minocycline also improve acne. It is believed that minocycline's anti-inflammatory effect also prevents acne.

Hormonal treatments

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.

If a pimple is large and/or does not seem to be affected by other treatments, a dermatologist may administer an injection of cortisone directly into it, which will usually reduce redness and inflammation almost immediately. This has the effect of flattening the pimple, thereby making it easier to cover up with makeup, and can also aid in the healing process. Side effects are minimal, but may include a temporary whitening of the skin around the injection point; and occasionally a small depression forms, which may persist, although often fills eventually. This method also carries a much smaller risk of scarring than surgical removal.

Topical retinoids

A group of medications for normalizing the follicle cell lifecycle are topical retinoids such as tretinoin (brand name Retin-A), adapalene (brand name Differin), and tazarotene (brand name Tazorac). Like isotretinoin, they are related to vitamin A, but they are administered as topicals and generally have much milder side effects. They can, however, cause significant irritation of the skin. The retinoids appear to influence the cell creation and death lifecycle of cells 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 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 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, however 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 anti-bacterial 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 may 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 lets 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. Occasionally 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 are 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.[48]

Sulfur

Sulfur has an inhibitory effect on the growth of Propionibacterium acnes and, when combined with sodium sulfacetamide (5% and 10%, respectively) has been shown to reduce acne with only mild side effects.[49]

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[43] 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 a CO2 or Er:YAG laser. Laser dermabrasion is much easier to control, much easier to gauge, and is practically bloodless compared to classic dermabrasion.

Microdermabrasion comes from the above mentioned technique dermabrasion. Microdermabrasion is a more natural skin care that is a gentler, less invasive technology for doing an exfoliation on the skin. The goal of the microdermabrasion is to eliminate the superficial layer of the skin called the epidermis. If the surface of the abraded skin is touched, a roughness of the skin will be noticed. The roughness is keratinocytes, which are better hydrated than the surface corneocytes. Keratinocytes appear in the basal layer from the proliferation of keratinocyte stem cells. They are pushed up through the cells of the epidermis, experiencing gradual specialization until they reach the stratum corneum where they form a layer of dead, flattened, strongly keratinized cells called squamous cells. This layer creates an efficient barrier to the entry of foreign matter and infectious elements into the body and reduces moisture loss. Keratinocytes are shed and restored continuously from the stratum corneum.

The time of transit from basal layer to shedding is generally one month. Corneocytes are cells derived from keratinocytes in the late stages of terminal specialization of squamous epithelia. The microdermabrasion is done to eliminate some of the corneocytes. These cells are responsible for the impermeability of the skin. The minimizing or elimination of scars, skin lesions, blotchiness and stretch marks from the skin can be an easy process with the use of skin exfoliation. The result depends on how well the procedure known as "skin remodeling" works. Results are optimal and fewer treatments are needed with more recent and/or superficial scars. Still, microdermabrasion can be used on scars that showed up during puberty or many years later.

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%[50] 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.[51] Particularly when applied over several days, these free radicals ultimately kill the bacteria.[52] Since porphyrins are not otherwise present in skin, and no UV light is employed, it appears to be safe, and has been licensed by the U.S. FDA.[53][54]

The treatment apparently 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;[55] 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 has 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, particularly when the P. acnes is pretreated with delta-aminolevulinic acid (ALA), which increases the production of porphyrins. However this photodynamic therapy is controversial and apparently 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.[56]

Surgery

For patients with cystic acne, boils can be drained through surgical lancing.[57]

Subcision

Subcision is a process used to treat deep rolling scars left behind by acne or other skin diseases. Essentially the process involves separating the skin tissue in the affected area from the deeper scar tissue. This allows the blood to pool under the affected area, eventually causing the deep rolling scar to level off with the rest of the skin area. Once the skin has leveled, treatments such as laser resurfacing, microdermabrasion or chemical peels can be used to smooth out the scarred tissue.

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.

In the United States, the FDA has approved several companies, such as Candela Corp., to use a cosmetic laser for the treatment of acne. However, efficacy studies have used very small sample sizes (fewer than 100 subjects) for periods of six months or less, and have shown contradictory results.[58] Also, laser treatment being relatively new, protocols remain subject to experimentation and revision,[59] 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.[60]

Less widely used treatments

  • Aloe vera: there are treatments for acne mentioned in Ayurveda using herbs such as Aloe vera, Neem, Haldi (Turmeric) and Papaya. There is limited evidence from medical studies on these products.[61] Products from Rubia cordifolia, Curcuma longa (commonly known as Turmeric), Hemidesmus indicus (known as ananthamoola or anantmula), and Azadirachta indica (Neem) have been shown to have anti-inflammatory effects, but not aloe vera.[62]
  • Azelaic acid (brand names Azelex, Finevin and Skinoren) is suitable for mild, comedonal acne.[63]
  • Calendula used in suspension is used as an anti-inflammatory agent.[64]
  • Cortisone injection into spots, also cortisone pills are sometimes used.
  • Comedo extraction
  • Heat: local heating may be used to kill the bacteria in a developing pimple and so speed healing.[65]
  • Naproxen or ibuprofen[66] are used for some moderate acne for their anti-inflammatory effect.
  • 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 topical antibiotic used for comparison.[67] Topical nicotinamide is available both on prescription and over-the-counter. The property of topical nicotinamide's benefit in treating acne seems to be its anti-inflammatory nature. It is also purported to result in increased synthesis of collagen, keratin, involucrin and flaggrin and may also according to a cosmetic company be useful for reducing skin hyperpigmentation (acne scars), increased skin moisture and reducing fine wrinkles.[68]
  • Pantothenic acid, (high dosage Vitamin B5)[69]
  • Rofecoxib was shown to improve premenstrual acne vulgaris in a placebo controlled study.[70]
  • Tea tree oil (melaleuca oil) dissolved in a carrier (5% strength) has been used with some success, where it is comparable to benzoyl peroxide but without excessive drying, kills P. acnes, and has been shown to be an effective anti-inflammatory in skin infections.[61][71][72]
  • Toothpaste is very effective at getting rip of Acne spots by drying up the skin.
  • Zinc: Orally administered zinc gluconate has been shown to be effective in the treatment of inflammatory acne, although less so than tetracyclines.[73][74]
  • Detoxification is a common method used by alternative medicine practitioners for the treatment of acne, although there have been no studies to prove its success. Detoxification is the process of cleansing the body of toxins purportedly caused by the environment, pharmaceutical drugs, food, and cosmetics.

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