Acne is a common problem in adolescents and young adults. The disorder is caused by abnormal desquamation of follicular epithelium that results in obstruction of the pilosebaceous canal. This obstruction leads to the formation of comedones, which can become inflamed because of overgrowth of Propionibacterium acnes. Topical retinoids such as tretinoin or adapalene are effective in many patients with comedonal acne. Patients with inflammatory lesions benefit from treatment with benzoyl peroxide, azelaic acid or topical antibiotics. Frequently, the use of comedonal and antibacterial agents is required.
Acne and its associated problems with self-esteem and social inhibition represent a figurative “rite of passage” for as many as 80 percent of adolescents and young adults.1,2 Two thirds of affected teenagers wish that they could speak with their physician about acne, but only one third actually do.3 It is important for family physicians to be knowledgeable about the treatment of this common disorder.
Topical preparations constitute the sole treatment in many patients with acne and are part of the therapeutic regimen in almost all patients. This article reviews topical acne preparations and provides information that can help family physicians select agents (or combinations of agents) that are appropriate in various situations.
Benzoyl peroxide, available over the counter and by prescription, has been a mainstay of acne treatment since the 1950s. This agent has bactericidal and comedolytic properties. It is the topical agent most effective against P. acnes, with bacteriostatic activity superior to that of topical antibiotics. It also functions as a mild comedolytic agent by increasing epithelial cell turnover with desquamation.
Benzoyl peroxide can be obtained in various concentrations (2.5 to 10 percent), although little evidence exists that efficacy is dependent on the dose.8 This agent comes in water-based or alcohol-based gels. The water-based formulations are less drying than the alcohol-based preparations. Benzoyl peroxide gels are applied once or twice daily.
Skin irritation is the most common side effect of benzoyl peroxide. This effect occurs more often at higher concentrations and tends to decrease with continued use. Contact allergy occurs in 1 to 2 percent of patients. Patients using benzoyl peroxide formulations for the first time should be instructed to test for allergic dermatitis by applying a small amount of the agent in the antecubital area before using it on the face.
Because benzoyl peroxide is an oxidizing agent, patients should be warned about potential bleaching of clothing and bed linens. This problem can be avoided by applying benzoyl peroxide to a clean, dry face in the morning and putting it on the face again at dinner time, if needed.
Salicylic acid is an ingredient of various over-the-counter preparations. It is available at a concentration of 0.5 or 2 percent in a number of creams and lotions. This agent inhibits comedogenesis by promoting the desquamation of follicular epithelium. It has been shown to be as effective as benzoyl peroxide in the treatment of comedonal acne. Salicylic acid is well tolerated and should be applied once or twice daily.
Sulfur preparations have been used to treat acne since the time of Hippocrates. Sulfur is combined with various other acne medications in many over-the-counter washes and cleansing bars. This agent has been shown to be effective in the treatment of inflammatory acne lesions, most likely as a result of keratolysis. However, efficacy may also be related to an irritative effect.
Preparations containing sulfur can cause some skin discoloration and can have a displeasing odor. Consequently, sulfur medications are now used less often in patients with acne.
The combination of sulfacetamide and sulfur (Novacet, Sulfacet-R) can be effective in the treatment of inflammatory skin lesions without the unpleasant side effects that occur with sulfur preparations alone. One study of sulfacetamide-sulfur lotion showed an 83 percent reduction in inflammatory lesions after 12 weeks of therapy.
Azelaic acid is a decarboxylic acid that was first investigated in the 1970s as a treatment for hyperpigmentation and was coincidentally found to be an effective acne treatment.14 In 1996, the U.S. Food and Drug Administration (FDA) labeled azelaic acid for the treatment of mild to moderate inflammatory acne. Although its exact mechanism of action is unknown, this agent has antibacterial and antikeratinizing activity, and it appears to be as effective as benzoyl peroxide or tretinoin (Retin-A) in the treatment of mild to moderate acne.15
Azelaic acid is available as a 20 percent cream (Azelex), which is applied twice daily to a clean, dry affected area. The agent is fairly well tolerated, with only about 5 percent of patients complaining of transient cutaneous irritation and erythema.16 This rate is lower than the incidence of such complaints reported for benzoyl peroxide and tretinoin. Because azelaic acid decreases pigmentation, it should be used with caution in patients with darker complexions.
Retinoids, which are derivatives of vitamin A, function by slowing the desquamation process, thereby decreasing the number of comedones and microcomedones. Retinoids are the most effective comedolytic agents in use. They have been a mainstay of acne treatment for the past 25 years.
Until recently, tretinoin was the only available topical retinoid. This agent is effective as monotherapy in patients with noninflammatory or mild to moderate inflammatory acne.17
Tretinoin is available as a cream, gel or liquid. The cream has the lowest potency, and the liquid has the highest potency. All tretinoin formulations can cause some skin irritation. The liquid is the most irritating, and the cream is the least irritating. The concentration of the agent also affects the degree of irritation.
Tretinoin should be applied in small amounts to clean, dry skin. Because the irritation associated with tretinoin is compounded by sun exposure, the formulation should be applied to affected areas once daily at bedtime. To assess irritation, a test dose should be applied and then washed off an hour or two later. To minimize irritation, tretinoin should be started at a low concentration, which can then be titrated upward as needed. Skin irritation usually decreases with continued therapy.
Patients should be warned that they may suffer a pustular flare during the first few weeks of tretinoin therapy. Rather than being an indication to stop or alter therapy, this pustular flare is a sign of the accelerated resolution of existing acne.
Because of the known teratogenic effects of oral vitamin A products, the use of tretinoin in pregnancy has been an issue of concern. Tretinoin is listed as a pregnancy category C drug. However, a study of 215 women exposed to tretinoin in the first trimester showed no increase in anomalies compared with control subjects.18 Individual physicians should decide if they are comfortable using this medication in pregnant women.
Tretinoin is now available in a new delivery system (Retin-A Micro) that may minimize its irritative effects. This delivery system works by entrapping the drug in microspheres that bring the medication more directly to the follicle and serve as reservoirs for the medication.19 The 0.1 percent tretinoin microsphere gel has been shown to be less irritating than 0.1 percent tretinoin cream.20
Adapalene (Differin) is a topical retinoid that was labeled by the FDA in 1997. Its mechanism of action is similar to that of tretinoin. Adapalene comes in a 0.1 percent gel or solution for application once daily in the evening.
Studies have shown that 0.1 percent adapalene gel is at least as effective as 0.025 percent tretinoin gel21 and significantly less irritating.22 Adapalene gel has not yet been compared with the newer tretinoin delivery system. Like tretinoin, adapalene may cause skin irritation and initial exacerbation of acne lesions.
Tazarotene (Tazorac) gel is a retinoid product that the FDA has labeled for use in the treatment of psoriasis and mild to moderate acne. It comes in a 0.05 or 0.1 percent gel for once-daily application. Studies comparing tazarotone with vehicle alone have shown that the medication is effective in treating noninflammatory acne lesions.23
Although comparative drug trials have not been performed, tazarotene and the standard form of tretinoin appear to have similar irritation rates. The use of tazarotene in pregnant women is not recommended.
Topical antibiotics work directly by killing P. acnes. Through their bactericidal activity, they also have a mild indirect effect on comedogenesis. These agents are available in a variety of forms and are applied once or twice daily.
Topical erythromycin and clindamycin (Cleocin T) are the most commonly used agents and have similar efficacy in patients with acne. Clindamycin has been shown to be significantly more effective than topical tetracycline.
Almost all topical antibiotics are associated with some minor skin irritation. This adverse effect may be influenced by the vehicle used.