Acne Cream 

Acne Cream

Acne vulgaris, also known as acne, is a long-term skin disease that occurs when hair follicles are clogged with dead skin cells and oil from the skin.

Acne is characterized by areas of blackheads or whiteheads, pimples, greasy skin, and possible scarring.

The resulting appearance can lead to anxiety, reduced self-esteem and, in ex...

Acne Cream

Acne vulgaris, also known as acne, is a long-term skin disease that occurs when hair follicles are clogged with dead skin cells and oil from the skin.

Acne is characterized by areas of blackheads or whiteheads, pimples, greasy skin, and possible scarring.

The resulting appearance can lead to anxiety, reduced self-esteem and, in extreme cases, depression or thoughts of suicide.

Genetics is thought to be the cause of acne in 80% of cases.

The role of diet and cigarette smoking is unclear and neither cleanliness nor sunlight appear to be involved.

Acne primarily affects areas of skin with a relatively high number of oil glands, including the face, upper part of the chest, and back.

During puberty, in both sexes, acne is often brought on by an increase in hormones such as testosterone. Excessive growth of the bacterium Propionibacterium acnes, which is normally present on the skin, is often involved.

Many treatment options for acne are available, including lifestyle changes, medications, and medical procedures.

Eating fewer simple carbohydrates (sugar) may help.

Treatments applied directly to the affected skin, such as azelaic acid, benzoyl peroxide, and salicylic acid, are commonly used.

Antibiotics and retinoids are available in formulations that are applied to the skin and taken by mouth for the treatment of acne.

However, resistance to antibiotics may develop as a result of antibiotic therapy. Several types of birth control pills help against acne in women.

Isotretinoin pills are usually reserved for severe acne due to greater potential side effects.

Early and aggressive treatment of acne is advocated by some to lessen the overall long-term impact to individuals.

In 2013, acne was estimated to affect 660 million people globally, making it the 8th most common disease worldwide.

Acne commonly occurs in adolescence and affects an estimated 80–90% of teenagers in the Western world.

Lower rates are reported in some rural societies.

Children and adults may also be affected before and after puberty.

Although acne becomes less common in adulthood, it persists in nearly half of people into their twenties and thirties and a smaller group continue to have difficulties into their forties.

• Classification

Acne severity classification as mild, moderate, or severe helps to determine the appropriate treatment regimen.

Open (blackheads) and closed (whiteheads) clogged skin follicles (comedones) limited to the face with occasional inflammatory lesions classically defines mild acne.

When a higher number of inflammatory papules and pustules occur on the face compared to mild cases of acne and also involve the trunk of the body, this defines moderate severity acne.

Lastly, when nodules (the painful 'bumps' lying under the skin) are the characteristic facial lesions and involvement of the trunk is extensive, severe acne is said to occur.

Large nodules were previously referred to as cysts, and the term nodulocystic has been used in the medical literature to describe severe cases of inflammatory acne.

However, true cysts are rare in those with acne and the term severe nodular acne is now the preferred terminology.

The skin condition hidradenitis suppurativa (HS) is commonly referred to as acne inversa.

Although HS shares certain common features with acne vulgaris, such as a tendency to clog skin follicles with skin cell debris, the condition otherwise lacks the defining features of acne and is therefore considered a distinct skin disorder.

Similarly, rosacea is sometimes referred to as acne rosacea, but is not a true form of acne.

• Signs and symptoms

Typical features of acne include increased secretion of oily sebum by the skin, microcomedones, comedones, papules, nodules (large papules), pustules, and in many cases scarring.

The appearance of acne varies with skin color. It may result in psychological and social problems.

• Scars

Acne scars are caused by inflammation within the dermal layer of skin and are estimated to affect 95% of people with acne vulgaris.

The scar is created by abnormal healing following this dermal inflammation.

Scarring is most likely to take place with severe nodular acne, but may occur with any form of acne vulgaris.

Acne scars are classified based on whether the abnormal healing response following dermal inflammation leads to excess collagen deposition or loss at the site of the acne lesion.

-Atrophic acne scars are the most common type of acne scar and have lost collagen from this healing response.

-Atrophic scars may be further classified as ice-pick scars, boxcar scars, and rolling scars.

-Ice-pick scars are narrow (less than 2 mm across), deep scars that extend into the dermis.

-Boxcar scars are round or ovoid indented scars with sharp borders and vary in size from 1.5–4 mm across.

-Rolling scars are wider than icepick and boxcar scars (4–5 mm across) and have a wave-like pattern of depth in the skin.

-Hypertrophic scars are uncommon, and are characterized by increased collagen content after the abnormal healing response.

They are described as firm and raised from the skin.

Hypertrophic scars remain within the original margins of the wound, whereas keloid scars can form scar tissue outside of these borders.

-Keloid scars from acne occur more often in men and people with darker skin, and usually occur on the trunk of the body.

• Pigmentation

Postinflammatory hyperpigmentation (PIH) is usually the result of nodular acne lesions. These nodular lesions often leave behind an inflamed darkened mark after the original acne lesion has resolved. Inflammation from acne lesions stimulates specialized pigment-producing skin cells (known as melanocytes) to produce more melanin pigment which leads to the skin's darkened appearance with PIH.

People with darker skin color are more frequently affected by this condition. Pigmented scar is a common term used for PIH, but is misleading as it suggests the color change is permanent.

Often, PIH can be prevented by avoiding any aggravation of the nodule, and can fade with time.

However, untreated PIH can last for months, years, or even be permanent if deeper layers of skin are affected. Even minimal skin exposure to the sun's ultraviolet rays can sustain hyperpigmentation. Daily use of SPF 15 or higher sunscreen can minimize acne-associated hyperpigmentation.

Causes

• Genes

The predisposition to acne for specific individuals is likely explained in part by a genetic component, a theory which has been supported by twin studies as well as studies that have looked at rates of acne among first-degree relatives.

Acne susceptibility is likely due to the influence of multiple genes, as the disease does not follow a classic Mendelian inheritance pattern. Multiple gene candidates have been proposed to increase acne susceptibility including certain variations in tumor necrosis factor-alpha (TNF-alpha), IL-1 alpha, and CYP1A1 genes, among others.

The 308 G/A single nucleotide polymorphism variation in the gene for TNF is associated with increased acne risk.

• Hormones

Hormonal activity, such as occurs during menstrual cycles and puberty, may contribute to the formation of acne. During puberty, an increase in sex hormones called androgens causes the skin follicle glands to grow larger and make more oily sebum.

Several hormones have been linked to acne, including the androgens testosterone, dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA), as well as growth hormone (GH) and insulin-like growth factor 1 (IGF-1).

Both androgens and IGF-1 seem to be essential for acne to occur, as acne does not develop in individuals with complete androgen insensitivity syndrome (CAIS) or Laron syndrome (insensitivity to GH, resulting in extremely low IGF-1 levels).

Medical conditions that commonly cause a high-androgen state, such as polycystic ovary syndrome, congenital adrenal hyperplasia, and androgen-secreting tumors, can cause acne in affected individuals.

Conversely, people who lack androgenic hormones or are insensitive to the effects of androgens rarely have acne.

An increase in androgen and oily sebum synthesis may also be seen during pregnancy.

Acne can be a side effect of testosterone replacement therapy or of anabolic steroid use.

Over-the-counter bodybuilding and dietary supplements are commonly found to contain illegally added anabolic steroids.

• Infections

Propionibacterium acnes (P. acnes) is the anaerobic bacterial species that is widely suspected to contribute to the development of acne, but its exact role in this process is not entirely clear.

There are specific sub-strains of P. acnes associated with normal skin and others with moderate or severe inflammatory acne.

It is unclear whether these undesirable strains evolve on-site or are acquired, or possibly both depending on the person. These strains have the capability of either changing, perpetuating, or adapting to the abnormal cycle of inflammation, oil production, and inadequate sloughing of dead skin cells from acne pores. Infection with the parasitic mite Demodex is associated with the development of acne.

However, it is unclear whether eradication of these mites improves acne.

• Diet

The relationship between diet and acne is unclear, as there is no high-quality evidence which establishes any definitive link.

High-glycemic-load diets have been found to have different degrees of effect on acne severity by different studies. Multiple randomized controlled trials and nonrandomized studies have found a lower-glycemic-load diet to be effective in reducing acne.

Additionally, there is weak observational evidence suggesting that dairy milk consumption is positively associated with a higher frequency and severity of acne.

Milk contains whey protein and hormones such as bovine IGF-1 and precursors of dihydrotestosterone. These milk components are hypothesized to promote the effects of insulin and IGF-1 and thereby increase the production of androgen hormones, sebum, and promote the formation of comedones.

Effects from other potentially contributing dietary factors, such as consumption of chocolate or salt, are not supported by the evidence.

Chocolate does contain varying amounts of sugar, which can lead to a high glycemic load, and it can be made with or without milk. Few studies have examined the relationship between obesity and acne. Vitamin B12 may trigger skin outbreaks similar to acne (acneiform eruptions), or worsen existing acne, when taken in doses exceeding the recommended daily intake.

• Smoking

The relationship between cigarette smoking and acne severity is unclear and remains controversial. The observational nature of the evidence between smoking and acne severity has raised concerns that bias and confounding may have influenced the results.

Some reviews have found that cigarette smoking worsens acne whereas others have found unclear effects.

Cigarette smoking is not recommended as an approach to improving the appearance of acne because of its adverse health effects.

• Stress

Overall, few high-quality studies have been performed which demonstrate that stress causes or worsens acne. While the connection between acne and stress has been debated, some research indicates that increased acne severity is associated with high stress levels in certain settings (e.g., in association with the hormonal changes seen in premenstrual syndrome).

• Pathophysiology

Hair follicle anatomy demonstrating a healthy hair follicle, a whitehead or closed comedone, and a blackhead or open comedone.

Acne vulgaris is a chronic skin disease of the pilosebaceous unit and develops due to blockages in the skin's hair follicles. These blockages are thought to occur as a result of the following four abnormal processes: a higher than normal amount of oily sebum production (influenced by androgens), excessive deposition of the protein keratin leading to comedone formation, colonization of the follicle by Propionibacterium acnes (P. acnes) bacteria, and the local release of pro-inflammatory chemicals in the skin.

The earliest pathologic change is the formation of a plug (a microcomedone), which is driven primarily by excessive growth, reproduction, and accumulation of skin cells in the hair follicle.

In normal skin, the skin cells that have died come up to the surface and exit the pore of the hair follicle.

However, increased production of oily sebum in those with acne causes the dead skin cells to stick together.

The accumulation of dead skin cell debris and oily sebum blocks the pore of the hair follicle, thus forming the microcomedone. This is further exacerbated by the biofilm created by P. acnes within the hair follicle.

If the microcomedone is superficial within the hair follicle, the skin pigment melanin is exposed to air, resulting in its oxidation and dark appearance (known as a blackhead or open comedone).

In contrast, if the microcomedone occurs deep within the hair follicle, this causes the formation of a whitehead (known as a closed comedone).

Dihydrotestosterone (DHT) is the main hormonal driver of oily sebum production in the skin. Another androgenic hormone responsible for increased sebaceous gland activity is DHEA-S.

Higher amounts of DHEA-S are secreted during adrenarche (a stage of puberty), and this leads to an increase in sebum production.

In a sebum-rich skin environment, the naturally occurring and largely commensal skin bacterium P. acnes readily grows and can cause inflammation within and around the follicle due to activation of the innate immune system.

P. acnes triggers skin inflammation in acne by increasing the production of several pro-inflammatory chemical signals (such as IL-1α, IL-8, TNF-α, and LTB4); IL-1α is known to be essential to comedone formation.

A major mechanism of acne-related skin inflammation is mediated by P. acnes's ability to bind and activate a class of immune system receptors known as toll-like receptors, especially toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4).

Activation of TLR2 and TLR4 by P. acnes leads to increased secretion of IL-1α, IL-8, and TNF-α.

Release of these inflammatory signals attracts various immune cells to the hair follicle including neutrophils, macrophages, and Th1 cells.

IL-1α stimulates increased skin cell activity and reproduction, which in turn fuels comedone development.

Sebaceous gland cells also produce more antimicrobial peptides, such as HBD1 and HBD2, in response to binding of TLR2 and TLR4.

P. acnes also provokes skin inflammation by altering the fatty composition of oily sebum.

Oxidation of the lipid squalene by P. acnes is of particular importance. Squalene oxidation activates NF-κB and consequently increases IL-1α levels.

Additionally, squalene oxidation leads to increased activity of the 5-lipoxygenase enzyme responsible for conversion of arachidonic acid to leukotriene B4 (LTB4). LTB4 promotes skin inflammation by acting on peroxisome proliferator-activated receptor alpha (PPARα).

PPARα increases activity of activator protein 1 (AP-1) and NF-κB, thereby leading to the recruitment of inflammatory T cells.

The inflammatory properties of P. acnes can be further explained by the bacterium's ability to convert sebum triglycerides to pro-inflammatory free fatty acids via secretion of the enzyme lipase.

These free fatty acids spur production of cathelicidin, HBD1, and HBD2, thus leading to further inflammation.

This inflammatory cascade typically leads to the formation of inflammatory acne lesions, including papules, infected pustules, or nodules. If the inflammatory reaction is severe, the follicle can break into the deeper layers of the dermis and subcutaneous tissue and cause the formation of deep nodules.

Involvement of AP-1 in the aforementioned inflammatory cascade also leads to activation of matrix metalloproteinases, which contribute to local tissue destruction and scar formation.

• Diagnosis

There are many features that may indicate a person's acne vulgaris is sensitive to hormonal influences. Historical and physical clues that may suggest hormone-sensitive acne include onset between ages 20 and 30; worsening the week before a woman's menstrual cycle; acne lesions predominantly over the jawline and chin; and inflammatory/nodular acne lesions.

Several scales exist to grade the severity of acne vulgaris, but no single technique has been universally accepted as the diagnostic standard.

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). This scale was the first to use a standardized photographic protocol to assess acne severity; since its creation in 1979, Cook's grading scale has undergone several revisions.

Leeds acne grading technique counts acne lesions on the face, back, and chest and categorizes them as inflammatory or non-inflammatory. Leeds scores range from 0 (least severe) to 10 (most severe) though modified scales have a maximum score of 12.

The Pillsbury acne grading scale simply classifies the severity of the acne from 1 (least severe) to 4 (most severe).

• Differential diagnosis

Skin conditions which may mimic acne vulgaris include angiofibromas, epidermal cysts, flat warts, folliculitis, keratosis pilaris, milia, perioral dermatitis, and rosacea, among others.

Age is one factor which may help distinguish between these disorders. Skin disorders such as perioral dermatitis and keratosis pilaris can appear similar to acne but tend to occur more frequently in childhood, whereas rosacea tends to occur more frequently in older adults.

Facial redness triggered by heat or the consumption of alcohol or spicy food is suggestive of rosacea. The presence of comedones can also help health professionals differentiate acne from skin disorders that are similar in appearance.

Chloracne, due to exposure to certain chemicals, may look very similar to acne vulgaris.

• Prognosis

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

Permanent physical scarring may occur.

There is good evidence to support the idea that acne has a negative psychological impact, and that it worsens mood, lowers self-esteem, and is associated with a higher risk of anxiety disorders, depression, and suicidal thoughts.

Another psychological complication of acne vulgaris is acne excoriée, which occurs when a person persistently picks and scratches pimples, irrespective of the severity of their acne.

This can lead to significant scarring, changes in the affected person's skin pigmentation, and a cyclic worsening of the affected person's anxiety about their appearance.

• Epidemiology

Globally, acne affects approximately 650 million people, or about 9.4% of the population, as of 2010.

It affects nearly 90% of people in Western societies during their teenage years, and may persist into adulthood.

Acne that first develops between the ages of 21 and 25 is uncommon; however, acne affects 54% of women and 40% of men older than 25 years of age.

Acne vulgaris has a lifetime prevalence of 85%. About 20% of those affected have moderate or severe cases. It is slightly more common in females than males (9.8% versus 9.0%). In those over 40 years old, 1% of males and 5% of females still have problems.

Rates appear to be lower in rural societies.

While some research has found it affects people of all ethnic groups, acne may not occur in the non-Westernized peoples of Papua New Guinea and Paraguay.

Acne affects 40–50 million people in the United States (16%) and approximately 3–5 million in Australia (23%).

In the United States, acne tends to be more severe in Caucasians than in people of African descent.

• Research

Efforts to better understand the mechanisms of sebum production are underway. The aim of this research is to develop medications targeting hormones known to increase sebum production (e.g., IGF-1 and alpha-melanocyte-stimulating hormone).

Additional sebum-lowering medications being researched include topical antiandrogens and peroxisome proliferator-activated receptor modulators.

Another avenue of early-stage research has focused on how to best use laser and light therapy to selectively destroy sebaceous glands in the skin's hair follicles to reduce sebum production and improve acne appearance.