Acne Vulgaris...Dr Ali Ahmad
Acne Vulgaris
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Acne vulgaris (or simply acne) is a chronic skin disease that occurs when hair follicles become blocked with dead skin cells and oil from the skin. Acne is characterized by comedones ( blackheads and whiteheads), pimples, greasy skin, and may lead to scarring.
Acne occurs most commonly during puberty. However, people may also be affected before and after puberty. Although it becomes less common in adulthood than in adolescence, approximately half of people in their twenties and thirties continue to have acne. Around 4% continue to have acne into their forties.
Classification
Acne is commonly classified by severity as mild, moderate, or severe. This type of classification can be an important factor in determining the appropriate treatment regimen.
Mild acne is classically defined as open (blackheads) and closed comedones (whiteheads) limited to the face with occasional inflammatory</u> lesions.
In moderate acne, a higher number of inflammatory papules and pustules occur on the face compared to mild cases of acne and acne lesions also occur on the trunk of the body.
Severe acne is said to occur when nodules and cysts are the characteristic facial lesions and involvement of the trunk is extensive.
Signs and symptoms
Typical features of acne include seborrhea (increased oil secretion), microcomedones, comedones, papules, pustules, nodules (large papules), and possibly scarring.The appearance of acne varies with skin color. It may result in psychological and social problems.
Scars
Acne scars are the consequence of an abnormal type of healing of inflammation within the dermal layer of skin and are estimated to affect 95% of people with acne vulgaris. Scarring is most likely to occur with severe nodulocystic 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 collagen 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 typically described as narrow (less than 2 mm across), deep scars that extend into the dermis. Rolling scars are wider than ice pick scars (45 mm across) and have a wave-like pattern of depth in the skin. Boxcar scars are round or ovoid indented scars with sharp borders and vary in size from 1.54 mm across.
Hypertrophic scars are less common 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 usually occur in men and on the trunk of the body rather than the face.
Pigmentation
Postinflammatory hyperpigmentation (PIH) is usually the result of nodular or cystic acne (the painful 'bumps' lying under the skin). They often leave behind an inflamed red mark after the original acne lesion has resolved. PIH occurs more often in people with darker skin color. Pigmented scar is a common but misleading term, as it suggests the color change is permanent. Often, PIH can be avoided by avoiding aggravation of the nodule or cyst. These scars can fade with time. However, untreated scars can last for months, years, or even be permanent if deeper layers of skin are affected.Daily use of SPF 15 or higher sunscreen can minimize pigmentation associated with acne.
Cause
Genetic
The predisposition for specific individuals to acne is likely explained in part by a genetic component, which has been supported by twin studies as well as studies that have looked at rates of acne among first degree relatives. The genetics of acne susceptibility is likely polygenic, as the disease does not follow classic Mendelian inheritance pattern. There are multiple candidates for genes which are possibly related to acne, including polymorphisms in TNF-alpha, IL-1 alpha, and CYP1A1 among others.The 308 G/A single nucleotide polymorphism in the gene for tumor necrosis factor (TNF) is associated with acne risk, especially in Caucasian individuals.
Hormonal
Hormonal activity, such as menstrual cycles and puberty, may contribute to the formation of acne. During puberty, an increase in sex hormones called androgens cause the follicular glands to grow larger and make more sebum. Several hormones have been linked to acne including the androgens testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone sulfate (DHEAS), as well as insulin-like growth factor 1 (IGF-1) and growth hormone.
Acne can be a side effect of testosterone replacement therapy or anabolic steroid use. Anabolic steroids are commonly found in over-the-counter bodybuilding supplements. A similar increase in androgens occurs during pregnancy, also leading to increased sebum production.
Acne that develops between the ages of 21 and 25 is uncommon.True acne vulgaris in adult women may be due to pregnancy or polycystic ovary syndrome.
Infectious
Propionibacterium acnes (P. acnes) is the anaerobic bacterium 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 either have the capability of changing, perpetuating, or adapting to, the abnormal cycle of inflammation, oil production, and inadequate sloughing of acne pores. One particularly virulent strain has been circulating in Europe for at least 87 years. Infection with the parasitic mite Demodex is associated with the development of acne. However, it is unclear if eradication of these mites improves acne.
Diet
The relationship between diet and acne is unclear as there is no high-quality evidence.The impact of a high glycemic load diet in studies has been mixed. 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 incidence and severity of acne. Other associations such as chocolate and salt are not supported by the evidence. Chocolate does contain a varying amount of sugar that can lead to a high glycemic load and it can be made with or without milk. There may be a relationship between acne and insulin metabolism and one trial found a relationship between acne and obesity. Vitamin B12 may trigger acneiform eruptions, or exacerbate existing acne, when taken in doses exceeding the recommended daily intake.
Smoking
Cigarette smoking is known to increase the risk of developing acne. Additionally, acne severity worsens as the number of cigarettes a person smokes increases.
Psychological
Overall, few high-quality studies have been performed that demonstrate stress causes or worsens acne. While the connection between acne and stress has been debated, some research indicates that increased acne severity in certain settings associated with high stress levels (e.g., in association with the hormonal changes seen in premenstrual syndrome).
Pathophysiology
Acne vulgaris is a chronic skin disease of the pilosebaceous unit and results from 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 sebum production (influenced by androgens), excessive keratin deposition leading to comedone formation, colonization of the follicle by Propionibacterium acnes bacteria, and the local release of pro-inflammatory chemicals in the skin. Severe acne is inflammatory, but acne can also be noninflammatory.
The earliest pathologic change is the formation of a plug (a microcomedone), which is driven primarily by excessive proliferation of keratinocytes 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. 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 (closed comedone). During adrenarche (a stage of puberty), a higher level of the androgen DHEA-S is secreted resulting in enlargement of the sebaceous glands and an increase in sebum production. However, dihydrotestosterone is the main driver of androgen-induced sebum production in the skin.
In a sebum-rich skin environment, the naturally occurring largely commensal skin bacterium Propionibacterium acnes readily grows and can cause inflammation within and around the follicle due to activation of the innate immune system. P. acnes is thought to provoke skin inflammation through multiple mechanisms that lead to increased expression of the pro-inflammatory chemical signal Interleukin-1-alpha (IL-1α), which is known to be crucial to the development of comedones. Activation of toll-like receptors such as toll-like receptor 2 and toll-like receptor 4 by P. acnes as well as oxidation of the fatty compound squalene in sebum (leading to activation of NF-κB) are thought to be major mechanisms responsible for increased IL-1α production. 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 deep to the epidermis and cause the formation of deep nodules and cysts (known as nodulocystic acne).
Diagnosis
There are several features that may indicate that 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/nodulocytic acne lesions.
Differential diagnosis
Skin conditions which may mimic acne vulgaris include rosacea, folliculitis, keratosis pilaris, perioral dermatitis, and angiofibromas among others. Age is one factor that may help a physician 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.
Management
Many different treatments exist for acne including benzoyl peroxide, antibiotics, retinoids, antiseborrheic medications, anti-androgen medications, hormonal treatments, salicylic acid, alpha hydroxy acid, azelaic acid, nicotinamide, and keratolytic soaps. They work in at least four different ways, including the following: normalizing skin cell shedding and sebum production into the pore to prevent blockage, killing P. acnes, anti-inflammatory effects, and hormonal manipulation.
Commonly used medical treatments include topical therapies such as retinoids, antibiotics, and benzoyl peroxide and systemic therapies including oral retinoids, antibiotics, and hormonal agents. Procedures such as light therapy and laser therapy typically have an adjunctive role and are not considered to be first-line treatments because of their high cost and limited evidence of efficacy.
Diet
A low glycemic index/glycemic load diet is recommended as a dietary method of improving acne.[38] As of 2014, evidence is insufficient to recommend milk restriction for this purpose.
Medications
Benzoyl peroxide cream
Benzoyl peroxide is a first-line treatment for mild and moderate acne due to its effectiveness and mild side-effects (mainly irritant dermatitis). It works against P. acnes, helps prevent formation of comedones, and has anti-inflammatory properties. Benzoyl peroxide normally causes dryness of the skin, slight redness, and occasional peeling when side effects occur. This topical does increase sensitivity to the sun as indicated on the package, so sunscreen use is often advised during the treatment to prevent sunburn. Benzoyl peroxide has been found to be nearly as effective as antibiotics with all concentrations being equally effective. Unlike antibiotics, benzoyl peroxide does not appear to generate bacterial resistance. Benzoyl peroxide may be paired with a topical antibiotic or retinoid such as benzoyl peroxide/clindamycin and benzoyl peroxide/adapalene, respectively.
Retinoids
Retinoids are medications that possess anti-inflammatory properties, normalize the follicle cell life cycle, and reduce sebum production. The retinoids appear to influence the cell life cycle in the follicle lining. This helps prevent the hyperkeratinization of these cells that can create a blockage. They are a first-line acne treatment, especially for people with dark colored skin and are known to lead to faster improvement of postinflammatory hyperpigmentation.
This class includes tretinoin, adapalene, and tazarotene. Like isotretinoin, these retinoids are related to vitamin A, but are administered topically and generally have much milder side effects. They can, however, cause significant irritation of the skin. Tretinoin is the least expensive of the topical retinoids and is the most irritating to the skin whereas adapalene is the least irritating to the skin but costs significantly more than other retinoids.Tazarotene is the most effective of the topical retinoids. However, tazarotene is also the most expensive and is not as well-tolerated as other topical retinoids.Retinol is a form of vitamin A that has similar, but milder effects and is used in many over-the-counter moisturizers and other topical products. Topical retinoids often cause an initial flare-up of acne and facial flushing. Generally speaking, retinoids increase skin's sensitivity to sunlight and are therefore recommended for use at night.
Isotretinoin, an oral retinoid, is very effective for severe nodulocystic acne as well as moderate acne refractory to other treatments. Improvement is typically seen after one to two months of use. Acne often resolves completely or gets much milder after a 4-6 month course of oral isotretinoin.After a single course, about 80% of people report an improvement with more than 50% reporting complete remission. About 20% of people require a second course. A number of adverse effects may occur including dry skin and lips, nose bleeds, muscle pains, increased liver enzymes, and increased lipid levels in the blood. There is no clear evidence that use of oral retinoids increases the risk of psychiatric side effects such as depression and suicidality.
u>Antibiotics
Topical antibiotics are frequently used for mild to moderate severe acne. Oral antibiotics are indicated for moderate to severe cases of inflammatory acne and decrease acne due to their anti-inflammatory properties and antimicrobial activity against P. acnes. Oral antibiotics are highly effective against inflammatory acne and produce faster resolution of inflammatory acne lesions than application of topical antibiotics. They are believed to work both by decreasing the number of bacterial and as an anti-inflammatory. With increasing resistance of P. acnes worldwide, they are becoming less effective. Commonly used antibiotics, either applied topically or taken orally, include erythromycin, clindamycin, metronidazole, sulfacetamide, and tetracyclines such as doxycycline and minocycline. It is recommended that oral antibiotics be stopped and topical retinoids be used once the disease has improved. Furthermore, the use of topical antibiotics alone is discouraged due to concerns surrounding antibiotic resistance and are recommended for use with topical benzoyl peroxide. Topical dapsone is not typically used as a first line antibiotic due to its higher cost and lack of clear superiority over other antibiotics.Dapsone is not recommended for use with benzoyl peroxide due to reports of yellow-orange skin discoloration with this combination of medications.
Salicylic acid
Salicylic acid is a topically applied beta-hydroxy acid that possesses bacteriostatic and keratolytic properties. Additionally, salicylic acid opens obstructed skin pores and promotes shedding of epithelial skin cells. Salicylic acid is known to be less effective than retinoid therapy. Dry skin is the most commonly seen side effect with topical application though darkening of the skin has been observed in individuals with darker skin types who use salicylic acid.
Azelaic acid
Azelaic acid has been shown to be effective for mild-to-moderate acne when applied topically at a 20% concentration. Application twice daily for six months is necessary, and treatment is as effective as topical benzoyl peroxide 5%, isotretinoin 0.05%, and erythromycin 2%. Treatment of acne with azelaic acid is less effective and more expensive than treatment with retinoids.Azelaic acid is thought to be an effective acne treatment due to its antibacterial, anti-inflammatory, and antikeratinizing properties. Additionally, azelaic acid has a slight skin-lightening effect due to its ability to inhibit melanin synthesis and is therefore useful in treatment of individuals with acne who are also affected by postinflammatory hyperpigmentation.Azelaic acid may cause skin irritation but is otherwise very safe.
Hormonal
In women, acne can be improved with the use of any combined oral contraceptive. Oral contraceptives decrease the ovaries' production of androgen hormones resulting in lower skin production of sebum and consequently improve acne severity. The combinations that contain third or fourth generation progestins such as desogestrel, norgestimate, or drospirenone may theoretically be more beneficial.A 2014 systematic review and meta-analysis found that oral antibiotics appear to be somewhat more effective than oral contraceptives at decreasing the number of inflammatory acne lesions at three months. However, the two therapies are approximately equal in efficacy at six months for decreasing the number of inflammatory, non-inflammatory, and total acne lesions. The authors of the analysis suggested that oral contraceptives may be a preferred first-line acne treatment over oral antibiotics in certain women due to similar efficacy at six months and a lack of associated antibiotic resistance.
Antiandrogens such as cyproterone acetate and spironolactone have also been used successfully to treat acne, especially in women with signs of excessive androgen production including increased hairiness, baldness, and increased skin production of oily sebum. The aldosterone antagonist spironolactone is an effective treatment for acne in adult women, but unlike combination oral contraceptives, is not approved by the United States' Food and Drug Administration for this purpose. Spironolactone is thought to be a useful acne treatment due to its ability to block the androgen receptor at higher doses. It may be used with or without an oral contraceptive. Hormonal therapies should not be used to treat acne during pregnancy or lactation as they have been associated with certain birth defects such as hypospadias and feminization of the male fetus. Finasteride is also likely to be an effective treatment for acne.
Combination therapy
Combination therapy using medications of different classes together, each with a different mechanism of action, has been demonstrated to be a more efficacious approach to acne treatment than mono therapy. The use of topical benzoyl peroxide and antibiotics together has been shown to be more effective than antibiotics alone. Similarly, using a topical retinoid with an antibiotic clears acne lesions faster than the use of antibiotics alone. Frequently used combinations include the following: antibiotic + benzoyl peroxide, antibiotic + topical retinoid, or topical retinoid + benzoyl peroxide. The pairing of benzoyl peroxide with a retinoid is preferred over the combination of a topical antibiotic with a retinoid since both regimens are effective but benzoyl peroxide does not lead to antibiotic resistance.
Procedures
Comedo extraction may temporarily help those with comedones that do not improve with standard treatment. A procedure for immediate relief is the injection of corticosteroids into the inflamed acne comedone.
Light therapy (also known as photodynamic therapy) is a method that involves delivering intense pulses of light to the area with acne following the application of a sensitizing substance (such as aminolevulinic acid or methyl aminolevulinate).[1][65] This process is thought to kill bacteria and decrease the size and activity of the glands that produce sebum. As of 2012, evidence for light therapy and lasers is insufficient to recommend them for routine use. Disadvantages of light therapy include its cost, the need for multiple visits, and the time required to complete the procedure. Light therapy appears to provide short-term benefit, but data for long-term outcomes and for those with severe acne is sparse. However, light therapy may have a role for individuals whose acne has been resistance to topical medications. Typical side effects of light therapy include skin peeling, temporary reddening of the skin, swelling, and postinflammatory hyperpigmentation.
Dermabrasion is an effective therapeutic procedure for reducing the appearance of superficial atrophic scars of the boxcar and rolling varieties.Ice pick scars do not respond well to treatment with dermabrasion due to their depth. However, the procedure is painful and has many potential side effects such as skin sensitivity to sunlight, redness, and decreased pigmentation of the skin. The procedure has fallen out of favor with the introduction of laser resurfacing. Unlike dermabrasion, there is no evidence that microdermabrasion is an effective treatment for acne.
Laser resurfacing can be used to reduce the scars left behind by acne. Ablative fractional photothermolysis laser resurfacing was found to be more effective for reducing acne scar appearance than non-ablative fractional photothermolysis, but was associated with higher rates of postinflammatory hyperpigmentation (usually about 1-month duration), facial redness (usually for 314 days), and pain during the procedure.
Chemical peels can also be used to reduce the appearance of acne scars. Mild chemical peels include those using glycolic acid, lactic acid, salicylic acid, Jessner's solution, or a lower concentration (20%) of trichloroacetic acid. These peels only affect the epidermal layer of the skin and can be useful in the treatment of superficial acne scars as well as skin pigmentation changes from inflammatory acne.Higher concentrations of trichloroacetic acid (30-40%) are considered to be medium strength peels and affect skin as deep as the papillary dermis. Formulations of trichloroacetic acid concentrated to 50% or more are considered to be deep chemical peels. Medium and deep strength chemical peels are more effective for deeper atrophic scars, but are more likely to cause side effects such as skin pigmentation changes, infection, or milia.
Pregnancy
In general, topically applied medications are considered the first line approach to acne treatment during pregnancy as topical therapies have little systemic absorption and are therefore unlikely to harm a developing fetus. Highly recommended therapies include topically applied benzoyl peroxide (category C) and azelaic acid (category B). Salicylic acid carries a category C safety rating due to higher systemic absorption (9-25%) and an association between the use of anti-inflammatory medications in the third trimester of pregnancy and adverse effects to the developing fetus including oligohydramnios and early closure of the ductus arteriosus. Prolonged use of salicylic acid over significant areas of the skin and under occlusive dressings is not recommended as this increases systemic absorption and the potential for fetal harm. Tretinoin (category C) and adapalene (category C) are very poorly absorbed but certain studies have suggested teratogenic effects in the first trimester. In studies examining the effects of topical retinoids during pregnancy, fetal harm has not been seen in the second and third trimesters. Retinoids contraindicated for use during pregnancy include the topical retinoid tazarotene (category X) and oral retinoids isotretinoin (category X) and acitretin (category X). Spironolactone is relatively contraindicated for use during pregnancy due to its antiandrogen effects.Finasteride is also not recommended for use during pregnancy as it is highly teratogenic.
Topical antibiotics deemed safe during pregnancy include erythromycin (category B), metronidazole (category B), and clindamycin (category B) due to negligible systemic absorption. Nadifloxacin and dapsone (category C) are other topical antibiotics that may be used to treat acne in pregnant women, but have received less extensive study. No adverse fetal events have been reported in association with topical use of dapsone during pregnancy. If retinoids are used during pregnancy, there is a high risk of abnormalities occurring in the developing fetus; therefore, women of childbearing age are required to use effective birth control if retinoids are used to treat acne.
Oral antibiotics considered safe for pregnancy (all category B) include cephalosporins, penicillins, and azithromycin. Tetracyclines (category D) are contraindicated during pregnancy as they are known to deposit in developing fetal teeth resulting in yellow discoloration and thinned tooth enamel. Use of tetracyclines in pregnancy has also been associated with development of acute fatty liver of pregnancy and should therefore be avoided.
Alternative medicine
Numerous natural products have been investigated for treating people with acne.Low-quality evidence suggests topical application of tea tree oil or bee venom may reduce the total number of skin lesions in those with acne. Tea tree oil is thought to be approximately as effective as benzoyl peroxide or salicylic acid but has been associated with cases of allergic contact dermatitis. Proposed mechanisms for tea tree oil's anti-acne effects include antibacterial action against P. acnes and anti-inflammatory properties. Numerous other plant-derived therapies have been observed to have positive effects against acne (e.g., basil oil and oligosaccharides from seaweed); however, few studies have been performed and most have been of lower methodological quality.There is a lack of high-quality evidence for the use of acupuncture, herbal medicine, and cupping therapy for acne.
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 worsens mood, lowers self-esteem, and is associated with a higher risk of anxiety, depression, and suicidal thoughts. Another psychological complication of acne vulgaris is acne excorie, 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.
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Dr Ali Ahmad
Email.
[email protected]
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