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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). Acne develops on the face and upper trunk. It most often affects adolescents. Diagnosis is by examination. Treatment, based on severity, can involve a variety of topical and systemic agents directed at reducing sebum production, comedone formation, inflammation, and bacterial counts and at normalizing keratinization.
Acne is the most common skin disease in the US and affects 80% of the population at some point in life.
Acne occurs through the interplay of 4 major factors:
Acne can be classified as
Comedones are sebaceous plugs impacted within follicles. They are termed open or closed depending on whether the follicle is dilated or closed at the skin surface. Plugs are easily extruded from open comedones but are more difficult to remove from closed comedones. Closed comedones are the precursor lesions to inflammatory acne.
Papules and pustules occur when P. acnes colonizes the closed comedones, breaking down sebum into free fatty acids that irritate the follicular epithelium and eliciting an inflammatory response by neutrophils and then lymphocytes, which further disrupts the epithelium. The inflamed follicle ruptures into the dermis (sometimes precipitated by physical manipulation or harsh scrubbing), where the comedone contents elicit a further local inflammatory reaction, producing papules. If the inflammation is intense, grossly purulent pustules occur.
Nodules and cysts are other manifestations of inflammatory acne. Nodules are deeper lesions that may involve > 1 follicle, and cysts are large fluctuant nodules.
The most common trigger is
During puberty, surges in androgen stimulate sebum production and hyperproliferation of keratinocytes.
Other triggers include
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.
Skin lesions and scarring can be a source of significant emotional distress. Nodules and cysts can be painful. 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. Papules are relatively deep. 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 and 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 of acne vulgaris 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 (see Table: Types of Drug Reactions and Typical Causative Agents). Acne severity is graded mild, moderate, or severe based on the number and type of lesions; a standardized system is outlined in Classification of Acne Severity.
Classification of Acne Severity
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.
It is important to treat acne to reduce the extent of disease, scarring, and psychologic distress.
Treatment of acne involves a variety of topical and systemic agents directed at reducing sebum production, comedone formation, inflammation, and bacterial counts and at normalizing keratinization (see Figure: How various drugs work in treating acne.). Selection of treatment is generally based on severity; options are summarized in 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 can be useful therapeutic adjuncts but are no longer commonly used.
Oral contraceptives are effective in treating inflammatory and noninflammatory acne, and spironolactone (beginning at 50 mg po once/day, increased to 100 mg po once/day after a few mo if needed) is another anti-androgen that is occasionally useful in women. Various light therapies, with and without topical photosensitizers, have been used effectively, mostly for inflammatory acne.
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.
Drugs Used to Treat Acne
Treatment of mild acne 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.
Dual therapy (eg, a combination of tretinoin with benzoyl peroxide, a topical antibiotic, or both) should be used to treat mild papulopustular (inflammatory) acne. 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.
Oral systemic therapy with antibiotics is the best way to treat moderate acne. 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. 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 may have more adverse effects with chronic use, including drug-induced lupus and hyperpigmentation.
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.
If the patient is female and unresponsive to oral antibiotics, a trial of oral antiandrogens (oral contraceptives and/or spironolactone) may be considered.
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 told that they are required 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.
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 (eg, polycystic ovary syndrome, virilizing adrenal tumors in females), 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.
If noninflammatory, acne is characterized by comedones and, if inflammatory, by papules, pustules, nodules, and cysts.
Mild and moderate acne usually heals without scarring by the mid 20s.
Recommend that patients avoid triggers (eg, occlusive cosmetics and clothing, cleansers, lotions, high humidity, some drugs and chemicals, possibly a high intake of milk or a high-glycemic diet).
Consider the psychologic as well as the physical effects of acne.
Prescribe a topical comedolytic (eg, tretinoin) plus, for inflammatory acne, benzoyl peroxide, a topical antibiotic, or both.
Prescribe an oral antibiotic for moderate acne and oral isotretinoin for severe acne.
Treat cystic acne with intralesional triamcinolone.
Drug NameSelect Brand Names
AmpicillinNo US brand name
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