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Acne vulgaris (acne) is the formation of comedones, papules, pustules, nodules, and/or cysts as a result of obstruction and inflammation of pilosebaceous units (hair follicles and their accompanying sebaceous gland). It most often affects adolescents. Diagnosis is by examination. Treatment is a variety of topical and systemic agents intended to reduce sebum production, bacterial counts, and inflammation and to normalize keratinization.
Pathophysiology
Acne occurs when pilosebaceous units become obstructed with plugs of sebum and desquamated keratinocytes then colonized with the normal skin anaerobe Propionibacterium acnes. Manifestations differ depending on whether P. acnes stimulates inflammation in the follicle; acne can be noninflammatory or inflammatory.
Comedones, uninfected sebaceous plugs impacted within follicles, are the signature of noninflammatory acne. Comedones are termed open or closed depending on whether the follicle is dilated or closed at the skin surface. Inflammatory acne comprises papules, pustules, nodules, and cysts.
Papules appear when lipases from P. acnes metabolize triglycerides into free fatty acids (FFA), which irritate the follicular wall. Pustules occur when active P. acnes infection causes inflammation within the follicle. Nodules and cysts occur when rupture of follicles due to inflammation, physical manipulation, or harsh scrubbing releases FFAs, bacteria, and keratin into tissues, triggering soft-tissue inflammation.
Etiology
The most common trigger is puberty, when surges in androgen stimulate sebum production and hyperproliferation of keratinocytes. Other triggers include hormonal changes that occur with pregnancy or the menstrual cycle; occlusive cosmetics, cleansers, lotions, and clothing; and high humidity and sweating. Associations between acne exacerbation and diet, inadequate face washing, masturbation, and sex are unfounded. Some studies suggest a possible association with milk products and high-glycemic diets. Acne may abate in summer months because of sunlight's anti-inflammatory effects. Proposed associations between acne and hyperinsulinism require further investigation. Some drugs and chemicals (eg, corticosteroids, lithium, phenytoin, isoniazid) worsen acne or cause acneiform eruptions.
Symptoms and Signs
Cystic acne can be painful; other types cause no physical symptoms but can be a source of significant emotional distress. Lesion types frequently coexist at different stages.
Comedones appear as whiteheads or blackheads. Whiteheads (closed comedones) are flesh-colored or whitish palpable lesions 1 to 3 mm in diameter; blackheads (open comedones) are similar in appearance but with a dark center.
Papules and pustules are red lesions 2 to 5 mm in diameter. In both, the follicular epithelium becomes damaged with accumulation of neutrophils and then lymphocytes. When the epithelium ruptures, the comedone contents elicit an intense inflammatory reaction in the dermis. Relatively deep inflammation produces papules. Pustules are more superficial.
Nodules are larger, deeper, and more solid than papules. Such lesions resemble inflamed epidermoid cysts, although they lack true cystic structure.
Cysts are suppurative nodules. Rarely cysts form deep abscesses. Long-term cystic acne can cause scarring that manifests as tiny, deep pits (icepick scars); larger pits; shallow depressions; or areas of hypertrophic scarring.
Acne conglobata is the most severe form of acne vulgaris, affecting men more than women. Patients have abscesses, draining sinuses, fistulated comedones, and keloidal and atrophic scars. The back and chest are severely involved. The arms, abdomen, buttocks, and even the scalp may be affected.
Acne fulminans is acute, febrile, ulcerative acne, characterized by the sudden appearance of confluent abscesses leading to hemorrhagic necrosis. Leukocytosis and joint pain and swelling may also be present.
Pyoderma faciale (also called rosacea fulminans) occurs suddenly on the midface of young women. It may be analogous to acne fulminans. The eruption consists of erythematous plaques and pustules, involving the chin, cheeks, and forehead.
Diagnosis
Diagnosis is by examination. Differential diagnosis includes rosacea (in which no comedones are seen), corticosteroid-induced acne (which lacks comedones and in which pustules are usually in the same stage of development), perioral dermatitis (usually with a more perioral and periorbital distribution), and acneiform drug eruptions. Acne severity is graded mild, moderate, or severe based on the number and type of lesions; a standardized system is outlined in Table 1: Acne and Related Disorders: Classification of Acne Severity .
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Table 1
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| Classification of Acne Severity |
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Severity
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Definition
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Mild
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< 20 comedones, or < 15 inflammatory lesions, or < 30 total lesions
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Moderate
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20 to 100 comedones, or 15 to 50 inflammatory lesions, or 30 to 125 total lesions
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Severe
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> 5 cysts, or total comedone count > 100, or total inflammatory lesion count > 50, or > 125 total lesions
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Prognosis
Acne of any severity usually remits spontaneously by the early to mid 20s, but a substantial minority of patients, usually women, may have acne into their 40s; options for treatment may be limited because of childbearing. Many adults occasionally develop mild, isolated acne lesions. Noninflammatory and mild inflammatory acne usually heals without scars. Moderate to severe inflammatory acne heals but often leaves scarring. Scarring is not only physical; acne may be a huge emotional stressor for adolescents who may withdraw, using the acne as an excuse to avoid difficult personal adjustments. Supportive counseling for patients and parents may be indicated in severe cases.
Treatment
Treatments are directed at reducing sebum production, comedone formation, inflammation, and bacterial counts (see Fig. 1: Acne and Related Disorders: How various drugs work in treating acne. ). Selection of treatment is generally based on severity; options are summarized in Table 2: Acne and Related Disorders: Drugs Used to Treat Acne. Affected areas should be cleansed daily, but extra washing, use of antibacterial soaps, and scrubbing confer no added benefit. A lower glycemic diet and moderation of milk intake might be considered for treatment-resistant adolescent acne. Peeling agents such as sulfur, salicylic acid, glycolic acid, and resorcinol are useful therapeutic adjuncts.
Treatment should involve educating the patient and tailoring the plan to one that is realistic for the patient. Treatment failure can frequently be attributed to lack of adherence to the plan and also to lack of follow-up. Consultation with a specialist may be necessary.
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Table 2
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| Drugs Used to Treat Acne |
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Drug
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Adverse Effects
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Comments
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Topical antibacterials
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Benzoyl peroxide 2.5%, 5%, and 10% gel, lotion, or wash
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Dry skin
Possible bleaching of clothing and hair
Allergic reactions (rarely)
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Comedolytic and antibacterial with very low to no development of resistance
Should be used in all patients if tolerated
Gel product usually preferred
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Benzoyl peroxide/erythromycin gel
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—
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Must be kept refrigerated
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Benzoyl peroxide/clindamycin gel
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—
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—
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Clindamycin 1% gel or lotion
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Diarrhea (rarely)
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Should be avoided in patients with inflammatory bowel disease
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Erythromycin 1.5 to 2% (multiple vehicles)
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Well-tolerated, but frequent development of bacterial resistance
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Topical comedolytics and exfoliants
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Tretinoin (0.025%, 0.05%, and 0.1% cream; 0.05% liquid; 0.025% and 0.1% gel)
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Skin irritation
Increased sun sensitivity
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Initial strength should be 0.025% and, if ineffective, should be increased; if irritation occurs, strength, frequency, or both should be reduced
When tretinoin is started, apparent worsening of acne, with improvement possibly taking 3 to 4 wk to occur
Requires use of protective clothing and sunscreen
Should be avoided during pregnancy
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Tazarotene 0.05% or 0.1% cream or gel
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Skin irritation
Increased sun sensitivity
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When tazarotene is started, apparent worsening of acne, with improvement possibly taking 3 to 4 wk to occur
Requires use of protective clothing and sunscreen
Should be avoided during pregnancy
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Adapalene 0.1% gel
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Some redness, burning, and increased sun sensitivity
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As effective as tretinoin but less irritating
Requires use of protective clothing and sunscreen
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Azelaic acid 20% cream
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Possible lightening of skin
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Minimally irritating
May be used by itself or with tretinoin
Should be used cautiously in people with darker skin because of skin-lightening effects
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Glycolic acid 5–10%
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Stinging
Mild irritation
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OTC product in cream, lotion, or solution; adjunct therapy
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Oral antibiotics
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Tetracycline 250–500 mg bid
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Increased sun sensitivity
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Inexpensive and safe, but must be taken on an empty stomach
Requires use of protective clothing and sunscreen
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Doxycycline 50–100 mg bid
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Increased sun sensitivity
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Good first-line drug in terms of efficacy and cost
Requires use of protective clothing and sunscreen
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Minocycline 50–100 mg bid
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Headache
Dizziness
Skin discoloration
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Most effective antibiotic but is expensive
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Erythromycin 250–500 mg bid
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Stomach upset
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Frequent development of bacterial resistance
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Oral retinoid
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Isotretinoin 1–2 mg/kg once/day for 16–20 wk
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Possible harm to a developing fetus
Possible effect on blood cells, the liver, and fat (triglyceride and cholesterol) levels
Dry eyes, chapped lips, drying of mucous membranes
Pain or stiffness of large joints and lower back with high dosages
Associated with depression, suicidal thoughts, attempted suicide, and (rarely) completed suicide
Unclear whether associated with new or worsened inflammatory bowel disease (Crohn disease and ulcerative colitis)
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For sexually active women, requires a pregnancy test before the start of therapy with isotretinoin and at monthly intervals during use of the drug plus use of 2 forms of contraception or sexual abstinence, beginning 1 mo before the drug is started, continued during drug use, and for 1 mo after stopping the drug
Requires periodic CBC, liver function tests, fasting glucose, and lipid profile
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Mild acne
Treatment should be continued for 6 wk or until lesions respond. Maintenance treatment may be necessary to maintain control.
Single-agent therapy is generally sufficient for comedonal acne. A mainstay of treatment for comedones is daily topical tretinoin as tolerated. Daily adapalene gel, tazarotene cream or gel, azelaic acid cream, and glycolic or salicylic acid are alternatives for patients who cannot tolerate topical tretinoin. Adverse effects include erythema, burning, stinging, and peeling. Adapalene and tazarotene are retinoids; like tretinoin, they tend to be somewhat irritating and photosensitizing. Azelaic acid has comedolytic and antibacterial properties by an unrelated mechanism and may be synergistic with retinoids.
Mild papulopustular (inflammatory) acne should usually be treated with dual therapy (eg, a combination of tretinoin with benzoyl peroxide, a topical antibiotic, or both). The topical antibiotic is usually erythromycin or clindamycin. Combining benzoyl peroxide with these antibiotics may help limit development of resistance. Glycolic acid may be used instead of or in addition to tretinoin. Treatments have no significant adverse effects other than drying and irritation (and rare allergic reactions to benzoyl peroxide).
Physical extraction of comedones using a comedone extractor is an option for patients unresponsive to topical treatment. Comedone extraction may be done by a physician, nurse, or physician assistant. One end of the comedone extractor is like a blade or bayonet that punctures the closed comedone. The other end exerts pressure to extract the comedone.
Oral antibiotics (eg, tetracycline, minocycline, doxycycline, erythromycin) can be used when wide distribution of lesions makes topical therapy impractical.
Moderate acne
Moderate acne responds best to oral systemic therapy with antibiotics. Antibiotics effective for acne include tetracycline, minocycline, erythromycin, and doxycycline. Full benefit takes ≥ 12 wk. Topical therapy as for mild acne is usually used concomitantly with oral antibiotics.
Tetracycline is usually a good first choice: 250 or 500 mg bid (between meals and at bedtime) for 4 wk or until lesions respond, after which it may be reduced to the lowest effective dose. Rarely, dosage must be increased to 500 mg qid. After control is achieved, it is reasonable to attempt to taper and discontinue the oral antibiotic and continue topical therapy for control. Because relapse often follows short-term treatment, therapy may need to be continued for months to years, although for maintenance tetracycline 250 or 500 mg once/day is often sufficient. Minocycline 50 or 100 mg bid causes fewer GI adverse effects, is easier to take, and is less likely to cause photosensitization, but it is the most costly option. Erythromycin and doxycycline are considered 2nd-line drugs because both can cause GI adverse effects, and doxycycline is a frequent photosensitizer. Subantimicrobial doses of doxycycline have also been proved effective for acne and rosacea.
Long-term use of antibiotics may cause a gram-negative pustular folliculitis around the nose and in the center of the face. This uncommon superinfection may be difficult to clear and is best treated with oral isotretinoin after discontinuing the oral antibiotic. Ampicillin is an alternative treatment for gram-negative folliculitis. In women, prolonged antibiotic use can cause candidal vaginitis; if local and systemic therapy does not eradicate this problem, antibiotic therapy for acne must be stopped.
Severe acne
Oral isotretinoin is the best treatment for patients with moderate acne in whom antibiotics are unsuccessful and for those with severe inflammatory acne. Dosage of isotretinoin is usually 1 mg/kg once/day for 16 to 20 wk, but the dosage may be increased to 2 mg/kg once/day. If adverse effects make this dosage intolerable, it may be reduced to 0.5 mg/kg once/day. After therapy, acne may continue to improve. Most patients do not require a 2nd course of treatment; when needed, it should be resumed only after the drug has been stopped for 4 mo. Retreatment is required more often if the initial dosage is low (0.5 mg/kg). With this dosage (which is very popular in Europe), fewer adverse effects occur, but prolonged therapy is usually required.
Isotretinoin is nearly always effective, but use is limited by adverse effects, including dryness of conjunctivae and mucosae of the genitals, chapped lips, arthralgias, depression, elevated lipid levels, and the risk of birth defects if treatment occurs during pregnancy. Hydration with water followed by petrolatum application usually alleviates mucosal and cutaneous dryness. Arthralgias (mostly of large joints or the lower back) occur in about 15% of patients. Increased risk of depression and suicide is much publicized but probably rare. It is not clear whether risk of new or worsened inflammatory bowel disease (Crohn disease and ulcerative colitis) is increased. CBC; liver function; and fasting glucose, triglyceride, and cholesterol levels should be determined before treatment. Each should be reassessed at 4 wk and, unless abnormalities are noted, need not be repeated until the end of treatment. Triglycerides rarely increase to a level at which the drug should be stopped. Liver function is seldom affected. Because isotretinoin is teratogenic, women of childbearing age are urged to use 2 methods of contraception for 1 mo before treatment, during treatment, and for at least 1 mo after stopping treatment. Pregnancy tests should be done before beginning therapy and monthly until 1 mo after therapy stops.
Intralesional injection of 0.1 mL triamcinolone acetonide suspension 2.5 mg/mL (the 10 mg/mL suspension must be diluted) is indicated for patients with firm (cystic) acne who seek quick clinical improvement with reduced scarring. Local atrophy may occur but is usually transient. For isolated, very boggy lesions, incision and drainage are often beneficial but may result in residual scarring.
Other forms of acne
Pyoderma faciale is treated with oral corticosteroids and isotretinoin. Acne fulminans is treated with oral corticosteroids and systemic antibiotics. Acne conglobata is treated with oral isotretinoin if systemic antibiotics fail. For acne caused by endocrine abnormalities, antiandrogens are indicated. Spironolactone, which has some antiandrogen effects, is sometimes prescribed to treat acne at a dose of 50 to 100 mg po once/day. Cyproterone acetate is used in Europe. When other measures fail, an estrogen/progesterone–containing contraceptive may be tried; therapy ≥ 6 mo is needed to evaluate effect.
Scarring
Small scars can be treated with chemical peels, laser resurfacing, or dermabrasion. Deeper, discrete scars can be excised. Wide, shallow depressions can be treated with subcision or collagen injection. Collagen implants are temporary and must be repeated every few years.
Key Points
Last full review/revision February 2013 by Karen McKoy, MD, MPH
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