Acne Vulgaris

Symptoms

The most common form of acne is known as "acne vulgaris", meaning "common acne." Excessive secretion of oils from the sebaceous glands accompanies the plugging of the pores with naturally occurring dead skin cells (corneocytes) blocking hair follicles. The accumulation of these corneocytes in the duct appears to be due to a failure of the normal keratinization process in the skin which usually leads to shedding of skin cells lining the pores. Oil secretions are said to build up beneath the blocked pore, providing a perfect environment for the skin bacteria Propionibacterium acnes and the lipophilic (oil/lipid-loving) yeast Malassezia to multiply uncontrollably. Under the microscope, however, there is no evidence of pooled trapped sebum. Indeed the oil percolates through the plugged duct onto the surface. In response to the bacterial and yeast populations, the skin inflames, producing the visible lesion. The face, chest, back, shoulders and upper arms are especially affected.

The typical acne lesions are: comedones, papules, pustules, nodules and inflammatory cysts. These are the more inflamed form of pus-filled or reddish bumps, even boil-like tender swellings. Non-inflamed 'sebaceous cysts', more properly called epidermoid cysts, occur either in association with acne or alone but are not a constant feature. After resolution of acne lesions, prominent unsightly scars may remain.

Aside from scarring, its main effects are psychological, such as reduced self-esteem and depression. Acne usually appears during adolescence, when people already tend to be most socially insecure.

Causes of Acne

Exactly why some people get acne and some do not is not fully known. It is known to be partly hereditary. Several factors are known to be linked to acne:

• Hormonal activity, such as menstrual cycles and puberty.
• Stress, through increased output of hormones from the adrenal (stress) glands.
• Hyperactive sebaceous glands, secondary to the three hormone sources above.
• Accumulation of dead skin cells.
• Bacteria in the pores, to which the body becomes 'allergic'.
• Skin irritation or scratching of any sort will activate inflammation.
• Use of anabolic steroids.
• Any medication containing halogens (iodides, chlorides, bromides), lithium, barbiturates, or androgens.
• Exposure to high levels of chlorine compounds, particularly chlorinated dioxins, can cause severe, long-lasting acne, known as Chloracne.

Traditionally, attention has focused mostly on hormone-driven over-production of sebum as the main contributing factor of acne. More recently, more attention has been given to narrowing of the follicle channel as a second main contributing factor. Abnormal shedding of the cells lining the follicle, abnormal cell binding ("hyperkeratinization") within the follicle, and water retention in the skin (swelling the skin and so pressing the follicles shut) have all been put forward as important mechanisms. Several hormones have been linked to acne: the male hormones testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone sulfate (DHEAS), as well as insulin-like growth factor 1 (IGF-I). In addition, acne-prone skin has been shown to be insulin resistant.

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 adults may be a feature of an underlying condition such as pregnancy and disorders such as polycystic ovary syndrome or the rare Cushing's syndrome. Dermatologists are seeing more cases of menopause-associated acne as fewer women replace the natural anti-acne ovarian hormone estradiol whose production fails as women arrive 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).

Misconceptions About Causes

There are many misconceptions and rumors about what does and does not cause the condition:

-Diet. One old and very poorly designed study suggested that chocolate, French fries, potato chips and sugar, among others, affect acne. Acne researchers tend to discount this study. On the other hand, a high GI (glycemic index) diet that causes sharp rises in blood sugar worsens acne. If this study's conclusions are verified then a low GI diet may help acne, but a recent review of somewhat dated scientific literature cannot affirm either way. A recent study, based on a survey of 47,335 women, did find a positive epidemiological association between acne and consumption of partially skimmed milk, instant breakfast drink, sherbet, cottage cheese and cream cheese. The researchers hypothesize that the association may be caused by hormones (such as several sex hormones and bovine IGF-I) present in cow milk. Although the association between milk and acne has been definitively shown, the ingredient in the milk responsible for the acne is still unclear. Most dermatologists are awaiting confirmatory research linking diet and acne but some support the idea that acne sufferers should experiment with their diets, and refrain from consuming such fare if they find such food affects the severity of their acne. Seafood, on the other hand, may contain relatively high levels of iodine. Iodine is known to make existing acne worse but there is probably not enough to cause an acne outbreak. Still, people who are prone to acne may want to avoid excessive consumption of foods high in iodine. It has also been suggested that there is a link between a diet high in refined sugars and other processed foods and acne. According to this hypothesis, the startling absence of acne in non-westernized societies could be explained by the low glycemic index of these cultures' diets. Others have cited possible genetic reasons for there being no acne in these populations, but similar populations shifting to Western diets do develop acne. Note also that the populations studied consumed no milk or other dairy products. Further research is necessary to establish whether a reduced consumption of high-glycemic foods (such as soft drinks, sweets, white bread) can significantly alleviate acne, though consumption of high-glycemic foods should in any case be kept to a minimum, for general health reasons. Avoidance of 'junk food' with its high fat and sugar content is also recommended. On the other hand there is no evidence that fat alone makes skin oilier or acne worse.

• Deficient personal hygiene - Acne is not caused by dirt. This misconception probably comes from the fact that comedones look like dirt stuck in the openings of pores. The black color is simply not dirt but compact 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. The bacteria involved are normally present on the skin but they multiply preferentially in the very low oxygen environment of these plugged pores. Very little variation among individuals with acne is due to hygiene. Anything beyond very gentle cleansing can actually worsen existing lesions and even encourage new ones by damaging or overdrying skin. On the other hand some commercial cleansers have been shown to help empty plugged pores.
• Sex -  Common myths state that masturbation causes acne and, conversely, that celibacy or sexual intercourse can cure it. Though it has been widely accepted that these are not true due to lack of scientific study on the subject, it is also important to note sexual activity has been observed to result in hormonal spikes, which has been linked to acne.

Treatments

Timeline of Acne Treatment

The history of acne reaches back to the dawn of recorded history. In Ancient Egypt, it is recorded that several pharaohs were acne sufferers. From Ancient Greece comes the English word 'acne' (meaning 'point' or 'peak'). Acne treatments are also of considerable antiquity:

Ancient Rome : bathing in hot, and often sulfurous, mineral water was one of the few available acne treatments. One of the earliest texts to mention skin problems is De Medicina by the Roman writer Celsus.

• 1800s: Nineteenth century dermatologists used sulphur in the treatment of acne. It was believed to dry the skin.
• 1920s: Benzoyl Peroxide is used.
• 1930s: Laxatives were used as a cure for what were known as 'chastity pimples'.
• 1950s: When antibiotics became available, it was discovered that they had beneficial effects on acne. They were taken orally to begin with. Much of the benefit was not from killing bacteria but from the anti-inflammatory effects of tetracycline and its relatives. Topical antibiotics became available later.
• 1960s: Tretinoin (original Trade Name Retin A) was found effective for acne. This preceeded the development of oral isotretinoin (sold as Accutane and Roaccutane) since the early 1980s.
• 1990s: Laser treatment introduced.
• 2000s: Blue/red light therapy.

Some old treatments, like laxatives, have fallen into disuse but others, like spas, are recovering their popularity.

Available Treatments

There are many products sold for the treatment of acne, many of them without any scientifically-proven effects. Generally speaking successful treatments give little improvement within the first week or two; and then the acne decreases over approximately 3 months, after which the improvement starts to flatten out. Treatments that promise improvements within 2 weeks are likely to be largely disappointing. Short bursts of cortisone, quick bursts of antibiotics and many of the laser therapies offer a quick reduction in the redness, swelling and inflammation when used correctly, but none of these empty the pore of all the materials that trigger the inflammation. Emptying the pores takes months.

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 P. acnes
• antinflammatory 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:

Exfoliating the Skin

This can be done either mechanically, using an abrasive cloth or a liquid scrub, or chemically. Common chemical exfoliating agents include salicylic acid and glycolic acid, which encourage the peeling of the top layer of skin to prevent a build-up of dead skin cells which combine with skin oil to block pores. It also helps to unblock already clogged pores. Note that the word "peeling" is not meant in the visible sense of shedding, but rather as the destruction of the top layer of skin cells at the microscopic level. Depending on the type of exfoliation used, some visible flaking is possible. Moisturizers and anti-acne topical containing chemical exfoliating agents are commonly available over-the-counter. Mechanical exfoliation is less commonly used as many benefits derived from the exfoliation are negated by the act of mechanically rubbing and irritating the skin.

Topical Bactericidal

Widely available OTC bactericidal products containing benzoyl peroxide may be used in mild to moderate acne. The gel or cream containing benzoyl peroxide is rubbed, 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. Unlike antibiotics, benzoyl peroxide has the advantage of being a strong oxidizer (essentially a mild bleach) and thus does not appear to generate bacterial resistance. 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 moisturizers to help avoid overdriving 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 antibacterial that have been used include triclosan, or chlorhexidine gluconate but these are often less effective.

Topical Antibiotics

Externally applied antibiotics such as erythromycin, clindamycin, Stiemycin or tetracycline aim to kill the bacteria that are harbored in the blocked follicles. Whilst topical use of antibiotics is equally as effective as oral, this method avoids possible side effects of stomach upset or drug interactions (e.g. it will not affect the oral contraceptive pill), but may prove awkward 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 behavior 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 will generally reappear quite soon after the end of treatment—days later in the case of topical applications, and weeks later in the case of oral antibiotics.

Hormonal Treatments

In females, acne can be improved with hormonal treatments. The common combined oestrogen/progestogen methods of hormonal contraception have some effect, but the anti-testosterone 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.

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. This method also carries a much smaller risk of scarring than surgical removal.

External Retinoid

Normalizing the follicle cell lifecycle. A group of medications for this are topical retinoid 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 retinoid 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 retinoid often cause an initial flare up of acne within a month or so, which can be severe.

Oral Retinoid

Reducing the secretion of oils from the glands. This is done by a daily oral intake of vitamin A derivatives like isotretinoin (marketed as Accutane, Sotret, Claravis) over a period of 4-6 months. It is believed that isotretinoin works primarily by reducing the secretion of oils from the glands, however some studies suggest that it affect 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 retinoid 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 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 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. This has occasioned widespread editorial comment.

Phototherapy

Blue and Red Light

It has long been known that short term improvement can be achieved with sunlight. However, studies have shown that sunlight worsens acne long-term, presumably due to UV damage. More recently, visible light has been successfully employed to treat acne (Phototherapy) - in particular intense blue light 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 blue 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 licensed by the U.S. FDA. The treatment apparently works even better if used with red visible light (660 nanometer) resulting in a 76% reduction of lesions after 3 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.

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 4 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. This is supported by a small number of user reports at Acne.org who have complained about photodynamic phototherapy having no effect or making the acne much worse. Out of 38 reviews 31,6% (12) experienced a long term cure, short term cure or an improvement, 28,9% (11) that there was no improvement or that it stopped working, 23,7% (9) that it got worse or much worse.

Less Widely Used Treatments

Azelaic acid (brand names Azelex, Finevin, Skinoren) is suitable for mild, comedonal acne.

• Zinc. Orally administered zinc gluconate has been shown to be effective in the treatment of inflammatory acne, although less so than tetracyclines.
• Tea Tree Oil (Melaleuca Oil) (tea tree oil) has been used with some success, and has been shown to be an effective anti-inflammatory in skin infections.
• Heat therapy - Zeno product uses heat at a specific temperature to kill bacteria and so treat mild to moderate acne.
• Niacinamide, (Vitamin B3) used topically in the form of a gel, has been shown in a 1995 study to be more effective than a topical antibiotic used for comparison, as well as having less side effects. Topical niacinamide is available both on prescription and over-the-counter. Some users choose to make their own at home, mixing together crushed niacinamide pills with aloe vera gel. The property of topical niacinamide's benefit in treating acne seems to be it's anti-inflammatory nature. It is also purported to result in increased synthesis of collagen, keratin, involucrin and flaggrin.

Future Treatments

Laser surgery has been in use for some time to reduce the scars left behind by acne, but research is now being 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 hyper pigmented macules (spots) or cause long term dryness of the skin. As of 2005, this is still mostly at the stage of medical research rather than established treatment.

Because acne appears to have a significant hereditary link, there is some expectation that cheap whole-genome DNA sequencing may help isolate the body mechanisms involved in acne more precisely, possibly leading to a more satisfactory treatment. (Crudely put, take the DNA of large samples of people with significant acne and of people without, and let a computer search for statistically strong differences in genes between the two groups). However, as of 2005 DNA sequencing is not yet cheap and all this may still be decades off. It is also possible that gene therapy could be used to alter the skin's DNA.

Phage therapy has been proposed to kill P.Acnes.

Preferred Treatments by Types of Acne Vulgaris

• Comedonal (non-inflammatory) acne: local treatment with azelaic acid, salicylic acid, topical retinoids, benzoyl peroxide.
• Mild papulo-pustular (inflammatory) acne: benzoyl peroxide or topical retinoid, topical antibiotics (such as erythromycin).
• Moderate inflammatory acne: benzoyl peroxide or topical retinoid combined with oral antibiotics (tetracyclines). Isotretinoin is an option.
• Severe inflammatory acne, nodular acne, acne resistant to the above treatments: isotretinoin, or contraceptive pills with cyproterone for females with virilization or drospirenone.

Acne Scars

Severe acne often leaves small scars where the skin gets a "volcanic" shape. Acne scars are difficult and expensive to treat, and it is unusual for the scars to be successfully removed completely. In those cases, acne scar treatment may be appropriate.

The psychological and emotional effects caused by acne scars can be as devastating to one's confidence as the acne itself.

Acne scars generally fall into two categories: physical scars and pigmented scars. Physical acne scars are often referred to as "Ice pick" scars. This is because the scars tend to cause an indentation in the skins surface. Pigmented scars is a slightly misleading term, suggesting a change in the skin's pigmentation. This is not 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. When sufferers try to 'pop' cysts or nodules, pigmentation scarring becomes significantly worse, and may even bruise the affected area. Pigmentation scars often fade with time, and those who suffered from acne before, and have developed scars are generally relieved that the acne has gone, and emotional effects of acne scars tend to be less distressing.

Acne scars are unsightly, and it is for this reason they can be psychologically and emotionally distressing. However, there are a range of treatments available. If acne scars are causing severe psychological distress, social withdrawal and/or emotional ill-health, a physician should be contacted.