Diagnosis and treatment of acne
American Family Physician, May 1, 2004 by Steven Feldman, Rachel E. Careccia, Kelly L. Barham, John Hancox
Acne is a disease of pilosebaceous units in the skin. It is thought to be caused by the interplay of four factors. Excessive sebum production secondary to sebaceous gland hyperplasia is the first abnormality to occur. (1) Subsequent hyperkeratinization of the hair follicle prevents normal shedding of the follicular keratinocytes, which then obstruct the follicle and form an inapparent microcomedo. (2) Lipids and cellular debris soon accumulate within the blocked follicle. This microenvironment encourages colonization of Propionibacterium acnes, which provokes an immune response through the production of numerous inflammatory mediators. Inflammation is further enhanced by follicular rupture and subsequent leakage of lipids, bacteria, and fatty acids into the dermis.
The diagnosis of acne is based on the history and physical examination. Lesions most commonly develop in areas with the greatest concentration of sebaceous glands, which include the face, neck, chest, upper arms, and back.
Acne vulgaris may be defined as any disorder of the skin whose initial pathology is the microscopic microcomedo. (3) The microcomedo may evolve into visible open comedones ("blackheads") or closed comedones ("whiteheads"). Subsequently, inflammatory papules, pustules, and nodules may develop. Nodulocystic acne consists of pustular lesions larger than 0.5 cm. The presence of excoriations, postinflammatory hyperpigmentation, and scars should be noted.
Acne may be triggered or worsened by external factors such as mechanical obstruction (i.e., helmets, shirt collars), occupational exposures, or medications. Common medications that may cause or affect acne are listed in Table 1. (4) Cosmetics and emollients may occlude follicles and cause an acneiform eruption. Topical corticosteroids may produce perioral dermatitis, a localized erythematous papular or pustular eruption. (5)
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Endocrine causes of acne include Cushing's disease or syndrome, polycystic ovary syndrome, and congenital adrenal hyperplasia. (6) Clinical clues to possible hyperandrogenism in women include dysmenorrhea, virilization (i.e., hirsutism, clitoromegaly, temporal balding), and severe acne.
In 1990, the American Academy of Dermatology developed a classification scheme for primary acne vulgaris. (7) This grading scale delineates three levels of acne: mild, moderate, and severe. Mild acne is characterized by the presence of few to several papules and pustules, but no nodules (Figure 1). Patients with moderate acne have several to many papules and pustules, along with a few to several nodules (Figure 2). With severe acne, patients have numerous or extensive papules and pustules, as well as many nodules (Figure 3).
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Acne also is classified by type of lesion--comedonal, papulopustular, and nodulocystic. Pustules and cysts are considered inflammatory acne.
Selection of topical therapy should be based on the severity and type of acne. Topical retinoids, benzoyl peroxide, and azelaic acid are effective treatments for mild acne. Topical antibiotics and medications with bacteriostatic and anti-inflammatory properties are effective for treating mild to moderate inflammatory acne. The dosage, approximate cost, and side effects of selected topical medications are summarized in Table 2.
Proper selection of topical formulations may decrease side effects and increase patient compliance. Fortunately, most acne medications are available in several forms. Creams and lotions typically are reserved for dry or sensitive skin, whereas gels are prescribed for oil-prone complexions. During treatment with prescribed medications, patients should use bland facial washes and moisturizers.
Retinoids and Retinoid Analogs. Topical tretinoin (Retin-A) is a comedolytic agent that normalizes desquamation of the epithelial lining, thereby preventing obstruction of the pilosebaceous outlet. (8) This agent also appears to have direct anti-inflammatory effects. (9) A derivative of vitamin A, tretinoin is available in cream, gel, and liquid forms. In tretinoin microsphere (Retin-A Micro), tretinoin is encapsulated in a polymer that slowly releases the active medication, resulting in less irritation than with other tretinoin preparations. (10) With all retinoids, visible improvement occurs after eight to 12 weeks of treatment.
Tretinoin is inactivated by ultraviolet (UV) light and oxidized by benzoyl peroxide. It therefore should be applied only at night and never with benzoyl peroxide. Tretinoin may decrease the amount of native UV protection by thinning the stratum corneum; thus, daily use of sunscreen is recommended. Because the irritation caused by tretinoin is dose-dependent, treatment should be initiated in a low dose. Patients only need a pea-sized amount of product per application.
There is no strong evidence for the teratogenicity of tretinoin, which remains pregnancy category C. A study (11) published in 1998 focused on the transdermal absorption of topical tretinoin and found the absorbed concentration to be below endogenous retinoid levels. However, no definitive consensus has been reached on the use of topical tretinoin in pregnancy. It may be wise to avoid use of topical retinoids or retinoid analogs in women who may become pregnant during treatment.
Adapalene (Differin) is a topical synthetic retinoid analog that normalizes differentiation of follicular epithelial cells and demonstrates direct anti-inflammatory properties. Double-blind studies have shown 0.1 percent adapalene gel to be as effective as 0.025 percent tretinoin gel. (12) [Evidence level A, meta-analysis] Adapalene is superior to 0.025 percent tretinoin gel in both tolerability and speed of efficacy, (12) and is equivalent in efficacy to 0.1 percent tretinoin microsphere. (13) [Reference 13--Evidence level A, randomized controlled trial (RCT)] Adapalene is a reasonable choice as a first-line topical retinoid; this agent may be especially useful in patients who are unable to tolerate the irritation caused by tretinoin.
Tazarotene (Tazorac) is available in 0.05 and 0.1 percent gel and cream formulations. It is a pregnancy category X agent. Tazarotene may be more irritating than other retinoids. Dose-related erythema and burning are the most common adverse effects. Studies have indicated that tazarotene gel is a more efficacious keratolytic than tretinoin 0.025 percent gel (14) and tretinoin 0.1 percent microsphere gel. (15) Because tazarotene may increase irritation, it usually is considered a second-line retinoid option in patients who have not responded to topical tretinoin or adapalene therapy.
Topical Antibiotics. These agents are another mainstay of acne treatment. Topical antibiotics commonly are used in conjunction with retinoids or benzoyl peroxide in patients with any degree of inflammatory acne. The most frequently used topical antibiotics are clindamycin and erythromycin. These drugs normally are applied once or twice daily.
Benzoyl Peroxide and Benzoyl Peroxide Combinations. Benzoyl peroxide is inexpensive and available over the counter. It has a stronger effect on papules than tretinoin, but a weaker effect on comedones. (16) Combinations of topical antibiotics and benzoyl peroxide increase efficacy and reduce antibiotic resistance in patients with P. acnes colonization. The preparations are available in gel form, and include 1 percent clindamycin with 5 percent benzoyl peroxide (BenzaClin) and 3 percent erythromycin with 5 percent benzoyl peroxide (Benzamycin). The preparations are equally effective in the treatment of acne. (17) [Evidence level B, single blinded RCT] One study18 comparing combined 1 percent clindamycin and 5 percent benzoyl peroxide with 1 percent clindamycin alone found the combination product to be more efficacious, with less P. acnes resistance. [Evidence level A, RCT]
Azelaic Acid. This agent is a dicarboxylic acid that has bacteriostatic and keratolytic properties. Azelaic acid (Azelex) may be particularly effective in the treatment of acne with postinflammatory hyperpigmentation. (19)
Other Topical Agents. Over-the-counter products may be used as primary or adjunctive treatments. Additional prescription topical agents include sulfacetamide (Klaron) and 10 percent sulfacetamide with 5 percent sulfur (Sulfacet-R). Sulfacetamide products are available in cream, gel, and wash formulations. These products generally are not considered first-line therapies, but they may be used in patients who cannot tolerate other topical agents.
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