Benzoyl peroxide (BP) is an antibacterial agent that kills P. acnes, the predominant organism in sebaceous follicles and comedones. BP releases free radical oxygen species that oxidize bacterial proteins. When included as an adjunct to an antibiotic regimen, control of acne is enhanced. Resolution of acne usually occurs within 4 to 6 weeks. BP is applied as a cream, lotion, or gel once or twice a day and can be left on or washed off. Washing BP off may be better tolerated in patients with sensitive skin.

Topical retinoids such as tretinoin, adapalene, and tazarotene are derivatives of vitamin A and are used for mild to moderate acne that alters keratinization. They are the mainstay of topical therapy because of their comedolytic activities, and they also have antiinflammatory actions. Retinoids alter the intracrine and paracrine mediators of cell differentiation and proliferation, apoptosis, and reproduction, thereby modifying gene expression, subsequent protein synthesis, and epithelial cell growth. Retinoids prevent horny cell cohesion, or keratolysis, and increase epithelial cell turnover. They do not affect microorganisms in acne and sebum production. Topical retinoids are appropriate for all types of acne when used in combination with other antiacne therapy. They also allow maintenance of acne clearance after discontinuing oral antibiotics. Of the retinoids, tazarotene is contraindicated with pregnancy. Retinoids should not be used before or after extended sun exposure or sunburn because they can increase the risk of sunburn and intensify existing sunburn.

Another antiacne topical agent, azelaic acid, has antibacterial, antiinflammatory, and mild comedolytic actions. Azelaic acid is as effective as BP and tretinoin combined. Salicylic acid is also a comedolytic treatment that is available over the counter in various strengths. However, the efficacy of salicylic acid is still unknown. Topical treatments with retinoids, azelaic acid, and salicylic acid can cause burning, pruritus, and erythema after several applications; however, they are less common with azelaic acid.

Moderate to severe acne may require a stronger concentration of BP, and topical antibiotics, such as tetracycline, erythromycin, and clindamycin, may be added to the treatment regimen. Erythromycin and clindamycin are the recommended topical antibiotics for acne therapy; however, erythromycin has reduced efficacy when compared with clindamycin. Topical antibiotics accumulate in the hair follicle and have both antiinflammatory and antibacterial effects. Topical antibiotics as monotherapy are not recommended due to the development of antibiotic resistance. Severe painful acne may be treated with steroid injection.

Isotretinoin, a derivative of vitamin A taken orally, is used for treatment of severe cystic acne that is not responsive to conventional therapy. It decreases sebum formation and secretion and has antiinflammatory and antikeratinizing (keratolytic) effects, decreasing lesions and scars due to acne. Additional benefits of isotretinoin include a decrease in anxiety and depression. The typical patient takes this drug for 4 to 6 months. Adverse reactions may occur that are dose dependent; these include chelitis, dizziness, cephalgia, conjunctivitis, skin irritation, pruritus, epistaxis, myalgia, arthralgia, temporary hair thinning, photosensitivity, depression, and suicidal thoughts. Usually, one course of treatment with isotretinoin is curative of severe acne. Because isotretinoin is a derivative of vitamin A, patients should not take vitamin A concomitantly. Using vitamin A or tetracycline with isotretinoin may increase its adverse effects. Baseline blood tests—liver function tests (LFTs), serum lipid panel, and pregnancy tests among female patients of childbearing age—are required before initiating isotretinoin therapy and at intervals throughout therapy. Isotretinoin must not be used during pregnancy; it is a known teratogen. Additional cautions associated with isotretinoin are to not breastfeed or to give blood during or for 1 month after therapy; patients should not take other medications or herbal products without first consulting their health care provider, drive at night without knowing the effect of isotretinoin on night vision, or have cosmetic procedures to smooth skin. Patient should be instructed to avoid excessively vigorous activity and to contact the health care provider and stop taking isotretinoin if they experience muscle weakness, which may be an indication of serious muscle damage.

Because of isotretinoin’s powerful teratogenicity, a risk-management system to prevent isotretinoin-related teratogenicity was implemented. iPLEDGE is the third risk-management program to prevent exposure to isotretinoin during pregnancy. Prior to starting isotretinoin therapy, both males and females must enroll in the iPLEDGE risk-management program and adhere to it. The program was created to ensure patients who receive isotretinoin use two forms of contraception, that no patient is pregnant when treatment is initiated, and that no patient becomes pregnant while taking the drug or for at least 1 month after completing a course of isotretinoin. This comprehensive program also has rules for the health care provider, patient, pharmacist, and wholesaler. Further information can be found at https://www.ipledgeprogram.com.

Topical corticosteroids are the principal treatment for the majority of patients. Corticosteroids are available in variety of vehicles that are sold over the counter (OTC) or by prescription; differing levels of potency are also available such that the weakest formula (e.g., 1% hydrocortisone) is available OTC, and the strongest (e.g., clobetasol propionate) is by prescription (see Box 45.1). Corticosteroids are classified according to their potency, class 1 to class 7, in which class 1 is the strongest (superpotent). The lower-potency topical steroids are reserved for sensitive skin (e.g., face, intertriginous areas, thin skin areas, in infants and older adults). Patients with thick skin and those with scales or plaques often require the highest-potency steroids. The usual length of treatment for most topical steroids is 4 weeks; otherwise, adverse effects that include cutaneous side effects and systemic absorption may occur. Tapering topical steroids after clinical response is recommended by the AAD. Cutaneous side effects include skin atrophy, telangiectasia, striae distensae, acne, folliculitis, and purpura. Other effects include worsening of existing or preexisting skin conditions (dermatoses) and fungal infections (tineas). Worsening of psoriasis can also occur (rebound effect) with the use of topical corticosteroids. Even though systemic side effects are fewer than cutaneous side effects with topical steroids, these can still occur. Systemic effects usually occur with the highest-potency preparation used over a large surface for a prolonged period. Examples of systemic side effects include Cushing syndrome, cataracts, glaucoma, and suppression of the hypothalamic-pituitary-adrenal (HPA) axis, which can cause growth retardation.

Synthetic vitamin D analogues (e.g., calcipotriene) bind to vitamin D receptors, enhancing the differentiation of keratinocytes while inhibiting their proliferation. Calcipotriene is available in solution, foam, and cream and is usually combined with topical corticosteroids to increase clinical response. Local side effects include burning, pruritus, edema, peeling, dryness, and erythema. Systemic side effects usually occur due to overapplication and include hypercalcemia and suppression of parathyroid hormone. Patients need to be instructed to avoid ultraviolet (UV) light because UVA inactivates calcipotriene.

Topical tazarotene, a retinoid, normalizes abnormal keratinocyte differentiation and decreases hyperproliferation and inflammation. Tazarotene may be used concurrently with moisturizers and topical corticosteroids. Common side effects include local irritation, although tazarotene is a teratogen.