Acne Vulgaris

Treatment

The treatment of acne ( Table I )[1,2,3,4,5,6] is based upon its severity (mild, moderate, severe) and the type(s) of lesion(s) present (noninflammatory, inflammatory, mixed). In general, the treatment of mild acne involves the use of topical agents, whereas the treatment of moderate and severe acne usually involves the use of both topical and systemic therapies or systemic therapy alone.

Mild comedonal (noninflammatory) acne may be treated with once daily application of a topical retinoid such as adapalene (0.1% cream; 0.1% gel; 0.1% solution; 0.1% pledgets), tretinoin (0.025%, 0.05%, 0.1% cream; 0.025%, 0.01%, 0.04%, 0.1% gel; 0.05% liquid), or tazarotene (0.05%, 0.1% cream; 0.05%, 0.1% gel). Topical retinoids act by modifying abnormal follicular keratinization. Other topical agents, such as azelaic acid (20% cream applied b.i.d.), salicylic acid (2%; various nonprescription products), and benzoyl peroxide (2.5%-10% gel applied q.d.), by virtue of their comedolytic or keratolytic activity, may also be effective for mild comedonal acne. Acne surgery, which manually removes comedones, may also be effective for comedonal acne.

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Mild inflammatory acne may be treated with azelaic acid, benzoyl peroxide, topical antibiotics, or a combination of these topical agents. Azelaic acid has anti-inflammatory and antibacterial activities. Azelaic acid also normalizes keratinization, which accounts for its anticomedogenic effect. Benzoyl peroxide has antibacterial activity. Topical antibiotics available for treating acne include clindamycin (1% gel, lotion, solution, or pledgets applied b.i.d.), erythromycin (2% gel, solution, or pledgets applied b.i.d.), and sodium sulfacetamide (10% lotion applied b.i.d.). Sulfur, which has antibacterial, anti-inflammatory, and keratolytic activity, is present in both prescription (5%, combined with sodium sulfacetamide) and over-the-counter (8%, combined with resorcinol) topical acne products. Many topical acne medications are now available as preformulated combinations, which may be applied twice a day. These include benzoyl peroxide plus clindamycin, benzoyl peroxide plus erythromycin, and sodium sulfacetamide plus sulfur.

Mild mixed (inflammatory and noninflammatory) acne may be treated with a topical retinoid (tretinoin, adapalene, or tazarotene) applied daily and azelaic acid, benzoyl peroxide, or topical antibiotics (clindamycin, erythromycin, or sulfacetamide) also applied daily. A retinoid may also be used in conjunction with one of the combination products described above.

Moderate comedonal acne is treated similarly to mild comedonal acne. Topical retinoids, azelaic acid, salicylic acid, and benzoyl peroxide are commonly used. The combination of a retinoid and azelaic acid, salicylic acid, and benzoyl peroxide can also be used, but may be irritating. Acne surgery is also effective.

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Moderate inflammatory and moderate mixed acne are treated with topical agents – similarly to mild inflammatory and mild mixed acne, respectively – though systemic therapy is also indicated. Systemic treatments used for moderate inflammatory and moderate mixed acne include oral antibiotics, oral contraceptives (for women), and nicotinamide. Oral antibiotics generally used in the treatment of acne are doxycycline, erythromycin, minocycline, sulfamethoxazole-trimethoprim, and tetracycline. Antibiotics reduce P. acnes levels. Their anti-inflammatory effects are achieved by reducing sebum free fatty acid levels. Tetracycline must be given on an empty stomach. The use of erythromycin can lead to resistant P. acnes strains. Doxycycline and minocycline may be more effective for acne than tetracycline. Rarely, minocycline can cause hypersensitivity, drug-induced lupus erythematosus, and hyperpigmentation. Doxycycline has a higher incidence of photosensitivity than other antibiotics used for acne. The hematologic status of patients on sulfamethoxazole-trimethoprim must be closely monitored.

Tetracycline is generally prescribed in divided doses of 500-1000 mg/day, although the lower dose can be given once daily. With improvement of acne, the dose may be reduced to 250 mg/day. Tetracycline should not be administered to patients younger than 8 years old.[7] Dosing for erythromycin is similar to tetracycline. Minocycline and doxycycline are prescribed in divided doses of 100-200 mg/day and can be lowered to 50 mg/day with improvement, although the lower dose can be administered once daily. Sulfamethoxazole-trimethoprim is prescribed as one double strength tablet twice daily, lowering to once daily with improvement.

Oral contraceptives (such as norgestimateethinyl estradiol) are effective in treating moderate acne in women unresponsive to topical treatment and/or oral antibiotics who have no contraindications to taking oral contraceptives. They act by reducing free testosterone. Improvement may not occur for up to 4 months following the start of therapy.

A combination of nicotinamide (750 mg), zinc oxide (25 mg), and folic acid (500 µg) is approved for the treatment of acne vulgaris (and rosacea). Both nicotinamide and zinc oxide have anti-inflammatory properties.

Severe comedonal acne is treated somewhat similarly to mild and moderate comedonal acne. Useful treatments include topical retinoids, azelaic acid, salicylic acid, benzoyl peroxide, or a combination of one of these with a retinoid. Acne surgery may also be helpful. Isotretinoin (see below) can be helpful in cases of severe comedonal acne, particularly those cases in which open comedones predominate.

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Severe inflammatory and severe mixed acne are treated similarly to moderate inflammatory acne. In addition to oral antibiotics, oral contraceptives, and nicotinamide, additional systemic therapies for severe inflammatory and severe mixed acne include high-dose tetracycline (1-3 g/day in divided doses), spironolactone, low-dose corticosteroids, isotretinoin, and dapsone.

Spironolactone, an androgen receptor blocker, may be used alone (25-200 mg/day) or in conjunction with other topical or systemic agents when treating women refractory to standard therapies or women with hyperandrogenism. Spironolactone is generally well tolerated, but may cause menstrual irregularities, breast tenderness, or hyperkalemia. Low-dose corticosteroids (such as dexamethasone, 0.125-0.5 mg q.h.s.) may also be effective for acne by suppressing adrenal androgen production.

Isotretinoin, a synthetic oral retinoid, is indicated for severe nodulocystic acne that is unresponsive to oral antibiotics. Isotretinoin is generally prescribed at a dose of 0.5-1 mg/kg daily for 4-5 months and can induce long-term remissions. Second and third courses are sometimes required. Common side effects include xerosis, cheilitis, and flaring of acne. Because of the risk of teratogenicity, women of childbearing age must not become pregnant while exposed to isotretinoin. The mechanism of action of isotretinoin is not completely understood, although it does inhibit sebaceous gland activity.

Dapsone (25-200 mg/day) is a useful treatment for recalcitrant nodulocystic acne. It has both anti-inflammatory and antibacterial effects. Since possible adverse effects include methemoglobinemia, hemolysis, and anemia, patients must have hematologic monitoring. A glucose-6-phosphate dehydrogenase level must be normal before beginning therapy.

Intralesional corticosteroids (such as triamcinolone acetonide, 2.5-10 mg/cc) are frequently effective in treating inflamed acne cysts and nodules. Newer treatments for acne include high-intensity blue light (405-420 nm) sources and a diode laser (1450 nm).

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