Acne vulgaris is caused by obstruction of the sebaceous follicles of the face and the trunk. Acne affects 80 percent of the population at some time between the ages of 11 and 30 years and can cause scarring and permanent disfigurement in some patients. Leyden reviews the pathophysiology of acne and outlines currently available topical and systemic therapies.
Topical therapies have no effect on the production of sebum, so scrubbing with soaps, detergents and astringents, which only remove sebum from the skin surface, does not reduce sebum production. In fact, vigorous scrubbing and the use of abrasive cleaners and mechanical devices can exacerbate acne. Gentle nonabrasive cleaning is best for removing sebum. Diet does not influence sebum production, so dietary restriction is not part of management.
Sebum production can be altered by systemic medications, but noticeable improvement does not occur until two to four months after therapy begins. Since sebaceous glands are androgen-dependent, estrogens and antian-drogens are useful therapies. Because of their feminizing properties, they should be used only in women. The beneficial effects of ethinyl estradiol are most apparent at doses of 50 μg or more. Newer oral contraceptives that contain 35 μg or less of ethinyl estradiol are not as effective, although lower dose oral contraceptives that include a nonandrogenic progesterone such as norgestimate or desogestrel can be effective. Spironolactone may also be effective in reducing sebum production and improving acne, even in doses as low as 25 to 50 mg daily.
Isotretinoin, a natural metabolite of vitamin A, greatly reduces sebum production. A four-to five-month oral course of isotretinoin, 0.1 to 1.0 mg per kg, results in remission in most patients. Remission lasts longer in patients treated with higher doses. Unfortunately, its use is limited by side effects such as arthralgia, stiffness, tendinitis and elevated serum lipid levels. Because it is teratogenic, isotretinoin therapy can only be initiated in women who are proved not pregnant. Effective contraception is essential during isotretinoin use and for at least one month following its discontinuation.
Topical agents, such as tretinoin, isotretinoin and salicylic acid, can be effective in slowing the desquamation of follicular epithelial cells. Tretinoin is available in several concentrations and can be used in combination with topical or systemic antibiotics. The gel formulation is preferred in hot and humid climates and the cream in cold and dry climates. Salicylic acid is weaker but is available over the counter. Azelaic acid is a recently approved agent with some activity against comedogenesis.
Topical antibiotics, when applied once or twice daily, have a beneficial effect as well. Various antibiotics may be used, including formulations of erythromycin, clindamycin, metronidazole, azelaic acid, benzoyl peroxide, and a combination of benzoyl peroxide and erythromycin or glycolic acid. Benzoyl peroxide suppresses the growth of Propionibacterium acnes more effectively than clindamycin and erythromycin alone. However, it causes local irritation and allergic contact dermatitis more often than other topical antibiotics. Topical clindamycin is more effective than topical erythromycin in vivo, but their clinical efficacy is similar. The combination of benzoyl peroxide and erythromycin is probably the most effective topical therapy available.
Systemic antibiotics for acne therapy include tetracycline, erythromycin, minocycline, doxycycline, clindamycin and trimethoprim-sul-famethoxazole. Doxycycline, minocycline and trimethoprim-sulfamethoxazole are generally considered more effective and less potent than tetracycline and erythromycin. All tetracyclines should be avoided until children have their permanent teeth. Absorption of doxycycline and minocycline is not reduced by dairy products and food to the same degree as tetracycline. The dosage can be tapered after four to six weeks once the development of new inflammatory lesions has stopped. Minocycline may cause vertigo-like symptoms. Doxycycline can induce photosensitivity. Erythromycin, although much less expensive than minocycline or doxycycline, causes gastrointestinal upset. Resistance is uncommon.
For most patients, a combination of drugs that addresses the abnormal desquamation and reduces the proliferation of P. acnes is sufficient to control acne, depending on the patient's skin characteristics. Increased sebum production and abnormal desquamation of epithelial cells can occur in children younger than 13 years, but colonization with P. acnes has not yet occurred. Therefore, treatment for this age group includes topical tretinoin, adapalene, azelaic acid or salicylic acid. In young teenagers, a mild form of inflammatory acne develops. Most patients in this age group respond after two to four weeks of twice-daily application of a topical antibiotic, topical benzoyl peroxide or the combination of benzoyl peroxide and erythromycin or other topical antibiotics.
The author concludes that patients with inflammatory acne are best treated with benzoyl peroxide, benzoyl peroxide plus erythromycin, topical clindamycin, topical erythromycin and/or oral antibiotics. Patients with widespread nodular cystic lesions may respond to oral antibiotics but generally require therapy with systemic isotretinoin. Estrogens or antiandrogens are effective alternatives to systemic isotretinoin in women with persistent acne.