Acne

Acne is a group of skin rashes that have different causes. It is a condition that affects humans as well as some mammals, and being the most common skin disease, it is considered by some as a part of the normal human growth process. It varies in its etiology, as well as its severity. Occasionaly a direct cause may be identified, while commonly no inciting agent is ever seen. It is an important and sometimes overlooked state, if left untreated, that could lead to a lifetime of disease sequelae such as scarring and skin hyperpigmentation. Some forms have been associated with even more severe acute manifestations that require emergent therapy. Some forms include:

• Acne vulgaris - most commonly experienced around puberty, typically of the face and shoulders/chest
• Acne rosacea - a red rash predominantly on the face
• Acne keloidalis nuchae (Pseudofolliculitis nuchae) - a rash caused by shaving
• Acne conglobata (Hidradenitis suppurativa) - chronic abscesses or boils of sweat glands and hair follicles; in the underarms, groin and buttocks, and under the breasts in women
• Acne fulminans - an extreme form of acne conglobata
• Acne cosmetica - acne caused by cosmetics
• Acne medicamentosa - acne caused by starting or stopping a medicine
• Baby acne - a rash seen on the cheeks, chin, and forehead of infants
• Chloracne - an acne rash caused by exposure to chlorinated hydrocarbons such as dioxins or PCBs

When used generically, the term "acne" refers to acne vulgaris. Eventhough broadly stated under the category of acne, the various conditions stated above are separate disease entities.

Acne vulgaris

Acne

Acne of a 14 year old boy during puberty
ICD-10	L70.0
ICD-O:	{{{ICDO}}}
ICD-9	706.1
OMIM	{{{OMIM}}}
MedlinePlus	000873
eMedicine	derm/2
DiseasesDB	10765

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

Acne vulgaris is an inflammatory disease of the skin, caused by changes in the pilosebaceous units (skin structures consisting of a hair follicle and its associated sebaceous gland). Acne lesions are commonly referred to as pimples, spots or zits.

Acne affects a large percentage of humans at some stage in life. The condition is most common during puberty and is considered an abnormal response to normal levels of the male hormone testosterone. The response for most people diminishes over time and acne thus tends to disappear, or at least decrease, after one reaches his or her early twenties. However, there is no way to predict how long it will take for it to disappear entirely, as some individuals will continue to suffer from acne decades later into their thirties, forties,and beyond.

Symptoms

File:Acne face.jpg

Acne of an older teenager.

The most common form of acne is known as "acne vulgaris." Excessive secretion of oils from the sebaceous glands (mostly due to gland enlargement during puberty), accompanied by the plugging of the pores with naturally occurring dead skin cells (corneocytes), results in a blockade of the 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. Once this defect in the keratinization process leads to these cells blocking the pore, the oil build up within the pore provides a favorable environment for the bacteria Propionibacterium acnes to multiply uncontrollably. In response to the bacterial populations, there is inflammation with attraction of white blood cells (neutrophils) to combat the bacteria, producing the visible lesion. The lesions have a propensity to affect the face, chest, back, shoulders and upper arms. The lesions occur as various forms and include: comedones, papules, pustules, nodules, and inflammatory cysts. Commonly, a pore that remains open (open comedo) but continues to distend with the keratinocytes, sebum oxidized by the bacteria, as well as the skin pigment melanin, is reffered to as a "blackhead". On the contrary, when a pore is occluded (closed comedo) by the dead skin cells, leading to accumulation of the materials below it, it is reffered to as a "whitehead." Cysts, pustules, papules, and nodules are more extensive lesions that usually arise when the accumulations within the pore rupture into the surrounding skin. The level of the rupture determines the severity of these lesions. After resolution of acne lesions, prominent unsightly scars may remain. Hyperpigmentation of the skin around the lesion also has been noted, especially in darker skinned individuals. Aside from scarring, its main effects are psychological, such as reduced self-esteem, depression, embarrassment, and rarely suicide. Acne usually appears during adolescence, when people already tend to be most socially insecure. Early and aggressive treatment is therefore advocated to lessen the overall impact to individuals.

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 stated above
• Accumulation of dead skin cells
• Bacteria in the pores, particularly Propionibacterium acnes
• Skin irritation or scratching, resulting in 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, causing severe, long-lasting acne, known as Chloracne

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 (PCOS) 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.

Acne cosmetica: Refers to acne caused by or made worse by cosmetics. The mechanism was presumably a chemically induced plugging of the pilosebaceous orifice. This was a significant problem for dermatologists in the 1970s and 1980s, but with the improved formulations produced by cosmetic chemists over the past thirty years, this is now a relatively rare diagnosis in daily practice.

The terms "non-comedogenic" appeared on moisturizers and other cosmetic compounds as re-formulations were introduced, sometimes associated with claims that the products were oil-free or water-based. Although early work produced lists of comedogenic chemicals in various strengths and vehicles, it became apparent that the actual comedogenicity of a product could not be predicted from its contents; rather the finished product itself needed to be use-tested.

The production of a low-grade folliculitis by some components of the cosmetic product has led to misdiagnosis on occasion.

Acne medicamentosa

Acne medicamentosa: refers to acne that is caused or aggravated by medication. Because acne is generally a disorder of the pilosebaceous units caused by hormones, the medications that trigger acne medicamentosa most frequently are hormones.

Although the male's hormone testosterone is most often blamed, and although men with acne secondary to bodybuilding hormones is seen from time to time, the major hormonal medication that causes acne is the progestin / progestagen present in birth control pills. Other medications can produce 'acneiform' eruptions (usually pimply bumps and pustules that look like acne).

Some conditions mimic acne medicamentosa. The most common mimic is the yeast folliculitis produced by an overgrowth of the Malassezia species, often secondary to oral or systemic corticosteroids, or secondary to broad-spectrum antibiotics such as the tetracycline family used in acne. This is often misinterpreted as 'tetracycline-resistant acne'.

There are many misconceptions about what does and does not cause the condition including diet, hygiene, and sexual activity. Various studies have been done, but the role of these factors still remains unclear and uncertain.

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.
• 1980s: Accutane is introduced in America
• 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 manifest usually after eight weeks, the time it takes for a comedone to mature completely. Other treatments may offer quick, temporary, relief as they reduce inflammation.

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
• 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:

For Comedonal Acne:

This type is mild in nature and is characterized by the presence of comedones without much surrounding inflammation. The treatment of this entity focuses on the correction of the abnormal follicular keratinization process. Drugs such as topical retinoids (ie. tretinoin, adapalene, tazorotene), are preffered and available only by prescription. Many over the counter preparations containing salicylic acid, benxoyl peroxide, or glycolic acid have also been found to have some use as they exhibit antimicrobial and comedolytic properties. They are especially useful when the side effects of the retinoids (excessive dry skin) can not be tolerated . Mechanical methods to open the pores are also used as an adjunct to the topical medications.

Cotton pads soaked in salicylic acid solution

Benzoyl peroxide cream.

For Mild to Moderate Inflammatory Acne:

As comedonal acne progresses with the appearance of increasing inflammatory lesions, combination therapy has proved to be very efficacious. A topical antibiotic (ie. erythromycin, clindamycin, metronidazole) along with a topical retinoid, are being used together with greater success than either agent alone. Benzoyl peroxide or adapalene are also being used in combinations with the topical antibiotics and topical retinoids with greater success than either agent alone..

For Moderate to Severe Inflammatory Acne:

As lesions progress to involve larger areas on the face as well as other body parts such as the back and trunk, topical therapies combining benzoyl peroxide, topical antibiotics, and topical retinoids are used to provide relief . Patients not responding to this therapy are requested to add an oral antibiotic (ie. tetracycline, doxycycline, trimethoprim-sulfamethoxazole, etc.) or isotretinoin . . It is important to note that isotretinoin carries potentially severe side effects that require strict monitoring and stringent guidelines before it is prescribed. Women that have been found to have hormonal abnormalities may also benefit from estrogen or antiandrogenic hormonal therapy .

Photo, Laser, and Heat Therapies

Of these various modalities that have been approved for the treatment of acne, phototherapy with high intensity narrow-band blue light (405 to 420nm) is the only therapy that has been proven to be efficacious in the treatment of acne The equipment or treatment, however, is relatively new and reasonably expensive, and therefore not generally recommended or used for this purpose.

Alternate treatments

These are treatments, generally home remedies, that are used with or without success around the world:

• Zinc - Orally administered zinc gluconate has been shown to be effective in the treatment of inflammatory acne
• Tea tree oil (Melaleuca oil)|Tea Tree Oil (Melaleuca Oil) - has been used with some success, and has been shown to be an effective anti-inflammatory agent in skin infections
• Niacinamide (Vitamin B3) - used topically in the form of a gel, the property of topical niacinamide's benefit in treating acne seems to be it's anti-inflammatory nature
• In some cases, people found bathing in salt water noticed lessened redness and decreased size in their acne.
• There are also certain treatments for acne mentioned in Ayurveda using herbs such as Aloevera, Aruna, Haldi, and Papaya.

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

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. However, 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 Propionibacterium acnes, and has seen some use.

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. Acne scars generally fall into two categories: physical scars and pigmented scars. Physical acne scars are often referred to as "Icepick" scars. This is because the scars tend to cause an indentation in the skins surface. Pigmented scars are usually the result of nodular or cystic acne. 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. The treatment for severe scarring is usually surgical in nature involving plastic surgery and laser therapies.

Acne fulminans

Acne fulminans, also known as Acne Maligna, is a rare severe form of acne.

Baby acne

Baby acne, also known as acne neonatorum, is a condition that affects roughly 20% of newborn babies. Lesions appear at around 2 weeks postpartum and commonly disappear after 3 months. Lesions include small, red, papules, which mainly affect the cheeks, as well as the nasal bridge of infants. Infants usually develop neonatal acne because of stimulation of the baby's sebaceous glands by lingering maternal hormones after delivery. These hormones cross the placenta into the baby and after delivery they cause the oil glands on the skin to form bumps that look like pimples.[1] Baby acne usually clears up within a few weeks, but it can linger for months.

Commonly mistaken for baby acne, tiny bumps on a baby's face after birth that disappear within a few weeks are called milia and are unrelated.

Baby acne has recently been described to be caused by saprophytic yeast of the Malassezia species, which cause a primary skin infection leading to the appearance of acne-like pustules. Initially it was believed to be the common yeast species, Malassezia furfur, which also causes 'cradle-cap' in infants. However, new publications have pointed to another species, Malassezia sympolais. Treatment options are still the same for both species, which includes low dose topical antifungals.

Chloracne

Acne Classification and external resources
File:Viktor Yuschenko.jpg
An example of chloracne on Viktor Yushchenko
ICD-10	L70.8
DiseasesDB	31706
eMedicine	topic/620  (Acneiform Eruptions)

Chloracne is an acne-like eruption of blackheads, cysts, and pustules associated with over-exposure to certain halogenic aromatic hydrocarbons, such as chlorinated dioxins and dibenzofurans. The lesions are most frequently found on the cheeks, behind the ears, in the armpits and groin region.

The condition was first described in German industrial workers in 1897 by Von Bettman, and was initially believed to be caused by exposure to toxic chlorine (hence the name "chloracne"). It was only in the mid-1950s that chloracne was associated with aromatic hydrocarbons. The substances that may cause chloracne are now collectively known as "chloracnegens".

Chloracne is particularly linked to toxic exposure to dioxins (byproducts of many chemical processes, including the manufacture of herbicides such as Agent Orange) — so much so that it is considered a clinical sign of dioxin exposure. The severity and onset of chloracne may follow a typical asymptotic dose response curve.

Etiology and progression

Chloracne normally results from direct skin contact with chloracnegens, although ingestion and inhalation are also possible causative routes.

Chloracnegens are fat-soluble, meaning they persist in the body fat for a very long period following exposure. Chloracne is a chronic inflammatory condition that results from this persistence, in combination with the toxin's chemical properties. It is believed, at least from rodent models, that the toxin activates a series of receptors promoting macrophage proliferation, inducing neutrophilia and leading to a generalised inflammatory response in the skin. This process may also be augmented by induction of excess tumor necrosis factor in the blood serum.

The inflammatory processes lead to the formation of keratinous plugs in skin pores, forming yellowish cysts and dark pustules. The skin lesions occur mainly in the face, but in more severe cases they involve the shoulders and chest, the back, and the abdomen. In advanced cases, the lesions appear also on the arms, thighs, legs, hands and feet.

In some instances, chloracne may not appear for three to four weeks after toxic exposure; however in other cases - particularly in events of massive exposure - the symptoms may appear within days .

Treatment

Once chloracne has been identified, the primary action is to remove the patient and all other individuals from the source of contamination. Further treatment is symptomatic.

Severe or persistent lesions may be treated with oral antibiotics or isotretinoin. However, chloracne may be highly resistant to any treatment.

The course of the disease is highly variable. In some cases the lesions may resolve within two years or so; however, in other cases the lesions may be effectively permanent (mean duration of lesions in one 1984 study was 26 years, with some workers remaining disfigured over three decades after exposure ).

Recent research by groups at University of Cincinnati School of Medicine in Ohio and the University of Western Australia indicated that PCB poisoning, including chloracne symptoms, can be treated with fat substitute olestra.

Related conditions

Chloracne is very often seen in combination with hyperhidrosis (clammy, sweaty skin) and porphyria cutanea tarda (a skin condition of increased pigmentation, hair coarsening and blistering).

Notable cases

• 193 cases of chloracne occurred in Seveso, Italy in 1976 following the Seveso disaster in which several kilograms of TCDD were released into the atmosphere.

• Hundreds of individuals suffered chloracne after chronic exposure to PCBs and PCDFs in central Taiwan in 1979.

• Ukrainian President Viktor Yushchenko suffered from extremely prominent facial chloracne after being diagnosed with dioxin poisoning in late 2004. His diagnosis of chloracne was put forth by prominent toxicologist John Henry.

References

ISBN links support NWE through referral fees

• James W (April 7 2005). Clinical practice. Acne.. N Engl J Med 352 (14): 1463-72. PMID 15814882.
• Webster G (31 August 2002). Acne vulgaris.. BMJ 325 (7362): 475-9. PMID 12202330.

External links

• Directory of rosacea organisations and websites
• National Rosacea Society (U.S.)
• Rosacea Research & Development Instititute (U.S.)

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