US Pharm. 2011;36(11):17-23.
Acne causes untold misery for millions of young people.1 Adolescents become the butt of cruel jokes and endure embarrassment that makes it hard to go to school every day. Parents and their children often ask pharmacists about acne and the utility of nonprescription products.
Prevalence of Acne
Acne is the most common dermatologic condition, affecting 40 to 50 million Americans each year. Up to 80% of those aged between 11 and 30 years have at least a minor version of the condition (acne vulgaris). However, it can occur at any age, and all races are affected.2-4
Epidemiology of Acne
Acne is more common during the teen years, for the reasons described below. However, other
situations worsen acne. Hormonal changes during pregnancy or initiating or ceasing therapy with oral contraceptives may be causal.2 Allowing oils to contact the face can plug pores. This may occur in patients intentionally placing an oil-based cosmetic or other material on the face (acne cosmetica), or in those exposed to atmospheres with oil, such as grill workers in restaurants. Pressure on the skin can also cause acne, as in those wearing bike or football helmets, tight collars, or backpacks (acne mechanica).3
Pathophysiology of Acne
While the exact causes of acne are unknown, it is thought to result from an unfortunate confluence of factors. One is the body changes that occur with puberty. Those changes affect the pilosebaceous unit, an area referred to as “the seat of acne.”2,5,6 The body’s pilosebaceous units contain a hair follicle and the associated sebaceous glands. Pilosebaceous units are lined with stratum corneum tissues, identical to the stratum corneum found in the outer layer of skin. On outer skin, the stratum corneum is constantly shed into the environment. However, inside the pilosebaceous unit, shed cells do not fall out into the environment but surround the hair follicle. Sebum from the sebaceous glands washes the shed cells to the surface of the skin or scalp, where they are removed by cleansers. At puberty, individual sebaceous glands grow into surrounding tissues, a process referred to as multilobulating. They produce more sebum when this occurs. Further, the stratum corneum cells develop an abnormal cohesion, and begin to narrow the lumen of the follicle.2,7 Thus, just at the time the pilosebaceous unit needs to be fully open to allow excessive sebum to escape, the follicular hyperkeratosis gradually shuts off outflow.
The Role of Bacteria
If outflow is sufficiently impeded, a plug can form from the hair, stratum corneum cells, and sebum.3 Bacteria in the plug cause inflammation, leading to its breakdown and resulting in acne lesions. The offending organism is Propionibacterium acnes. It lives on the fatty acids in sebum, producing propionic acid, which is inflammatory to tissues.
The Lesions of Acne
Acne lesions are of two types, noninflammatory and inflammatory.8 The initial acne lesion is a small pimple beneath the surface of the skin known as the whitehead.2,3 As the whitehead continues to grow, the top of the pore opens, exposing the upper layers of material to the air. Oxidation discolors the upper section of the plug to produce a brown to black color, resulting in the familiar blackhead. It is critical to note that the discoloration is not accumulated dirt, as this misconception leads to ill-advised cleaning regimens that can damage the skin. Whiteheads and blackheads are both noninflammatory lesions.9
Inflammatory acne lesions include papules, pustules, and nodules. Papules are small, tender bumps with an erythematous halo. They progress to painful pustules with erythema, but also exhibiting visible pus at the apex. Nodules may appear next, as larger (>5 mm in diameter), painful/tender erythematous solid pimples deep in the skin. Eventually, the patient may develop cysts that are deep, painful, and pus-filled. Once cysts develop, scarring will almost always follow.
Rating Acne Severity
Several scales can be used to rate acne severity. However, the Center for Drug Evaluation and Research recommends the Investigator’s Global Assessment (IGA) scale for the development of acne medications.8 Grade 0 denotes clear skin with no lesions. Grade 1 is skin that is almost clear, with a few noninflammatory lesions but no more than one small inflammatory lesion. Grade 2 acne is of mild severity, with inflammatory lesions, but no more than a few inflamed lesions (papules or pustules only). Grade 3 acne is of moderate severity, with many noninflamed lesions and some inflammatory lesions, but not more than one small nodular lesion. Grade 4 acne is severe, with many noninflamed and inflamed lesions, and a few nodular lesions.
Nonprescription Products for Acne
Nonprescription acne products are not appropriate for the more severe forms of acne. In its final rule on nonprescription topical acne products, the FDA limited OTC labeling to treatment of acne blemishes, pimples, blackheads, and whiteheads.9 The FDA defined blemishes as flaws resulting from acne and pimples as small, prominent, inflamed skin elevations. Thus, labeling appears to contraindicate their use in nodular or cystic acne. Products approved for acne include sulfur, sulfur/resorcinol combinations, salicylic acid, and benzoyl peroxide (see Patient Information).2
FDA’s Final Rule on Acne Product Labeling
Benzoyl peroxide underwent additional scrutiny to assess its safety and efficacy for acne; in the process, the FDA finalized labeling for acne products. Like the other ingredients previously mentioned, benzoyl peroxide was judged to be safe and effective in the original 1982 acne panel deliberations, when used in a 2.5% to 10% concentration.10 The FDA agreed with this conclusion in its 1985 notice of proposed rulemaking (tentative final monograph).11
In 1991, the FDA issued an amendment to the tentative final monograph reclassifying benzoyl peroxide from Category I (safe and effective) to Category III (more data needed) status.12 The agency explained that this unusual move was a response to information it had received since the 1985 report. Two studies indicated that benzoyl peroxide might possess tumor promotion or tumor initiation potential. The FDA evaluated the studies and subsequently concluded that benzoyl peroxide did appear to be a skin tumor promoter in mice and other laboratory animals. The FDA asked for additional studies of 18 to 24 months’ duration in two species (mouse and rat) to determine benzoyl peroxide’s potential for carcinogenicity. The agency promised to consider the wisdom of allowing continued marketing during the time that the carcinogenicity studies were underway.12
In 1995, the FDA proposed additional labeling for benzoyl peroxide to address the safety of continued marketing.13 The agency explained that it would not restrict sales pending a final determination, but explained that the proposed labeling would help ensure safe use. Labeling would warn against unnecessary sun exposure and would also direct patients to use a sunscreen when going outdoors.
The issue of benzoyl peroxide’s carcinogenicity was not settled until 2010.9 In a final rule, the FDA stated that it had examined newly submitted studies and concluded that adequate labeling could minimize the risks associated with benzoyl peroxide while allowing patients to obtain effective acne treatment, in effect reclassifying the ingredient as safe and effective (Category I). In that document, the agency also reconsidered labeling for other acne ingredients (e.g., sulfur, sulfur/resorcinol, salicylic acid) and issued a final revision affecting all safe and effective acne ingredients. The rules became or will become mandatory on March 4, 2011 (benzoyl peroxide products with annual sales ≥$25,000), March 2, 2012 (benzoyl peroxide products with annual sales <$25,000), and March 4, 2015 (sulfur, sulfur/resorcinol, and salicylic acid products).
Warning labels for all acne products will advise patients that dryness is more likely if two products are used at the same time, and to use only one product if irritation occurs. Products containing sulfur will caution patients to use them only on areas affected with acne and will warn against use on large parts of the body or on broken skin. Products containing the combination of resorcinol and sulfur will warn patients to rinse them immediately from the eyes after accidental contact, and to stop use and ask a physician if skin irritation occurs or worsens. Benzoyl peroxide products will warn patients against use if they have sensitive skin, and to avoid contact with the eyes, lips, and mouth. The FDA also required preliminary sun warnings, so that these products will advise against unnecessary sun exposure and recommend the use of sunscreen. Other warnings will state that benzoyl peroxide may bleach hair and dyed fabrics and may cause skin irritation, characterized by redness, burning, itching, peeling, or inflammation, all of which may be eased by using the product less often or in a lower concentration. Finally, benzoyl peroxide products will warn patients to stop use and seek physician assistance if irritation becomes severe.9
Acne Myths
As the pharmacist counsels patients with acne, they may ask about popular myths regarding its causes. For instance, patients often believe that certain foods or drinks cause or worsen acne. They may ask specifically about fried foods, caffeine-containing drinks, potato chips, or chocolate. While it may be advisable to limit intake of all of these foods and drinks, it cannot be said with any degree of certainty that limiting them or eliminating them will improve or stop acne.9 Another myth is that dirty skin leads to acne. Patients should be cautioned to avoid overwashing with harsh sponges or scrubbing with pressure, as either can actually damage the delicate skin and worsen the acne.2,14,15 Rather, oils and dirt on the skin should be removed by gently washing once or twice daily with a nondrying soap or facial cleanser (e.g., Basis, CeraVe, Cetaphil, Dove, Neutrogena).
Acne Tips
Patients should be urged not to scratch, squeeze, pick, or rub their acne lesions. Doing so can lead to infection and scarring. Patients should avoid tight headbands, baseball caps, and other types of hats and helmets whenever possible, to avoid acne due to friction against the skin. They should shampoo the hair daily, especially if they have oily hair. The hair should be combed or pulled back out of the face to minimize oil transfer. Hands and fingers should be kept away from the face. For instance, listening to lectures with the chin cupped in one hand can cause acne in the identical areas touched by the hand. Makeup should be water-based and noncomedogenic, and should be removed at night.15
PATIENT INFORMATION
Nonprescription Products for Acne
If your acne is not too severe, safe and effective nonprescription products can provide relief. None of them will cure acne, but reducing its severity may be enough. You should not combine acne medications, as doing so could worsen dryness and irritation of the skin.
Cleanse the skin by gently washing with a mild soap before applying acne products. The first time you try a new product, apply it sparingly in a thin layer to just a few small areas once daily. Reapply it in the same manner for 2 more days. If you notice that painful burning or irritation occurs, it may be best to try another product. If the substance produces only a mild adverse reaction, you may wish to continue to use it and apply it to all affected areas. Eventually, you can begin to apply it two or three times daily, as directed on the label. You may also choose a product with a higher concentration of active ingredient. If dryness or peeling becomes troublesome, you should reduce application to once daily or once every other day.
Ingredients to look for include benzoyl peroxide, sulfur, sulfur/resorcinol, and salicylic acid. Examples of benzoyl peroxide trade names include Clearasil Daily Clear Acne Treatment Cream, Neutrogena On-the-Spot Acne Treatment, PanOxyl 4, Proactiv, and ZapZyt Gel. If you develop redness, burning, swelling, peeling, or itching, stop using the product. Keep it away from the eyes, mouth, and lips, and stay out of the sun while using it. Benzoyl peroxide can bleach hair or fabric due to its peroxide content.
A product containing a combination of sulfur and resorcinol is Clearasil Daily Clear Adult Treatment Cream. It should not be applied to large areas of the skin or skin that is broken.
Products containing salicylic acid include Clean & Clear Advantage Mark Treatment, Neutrogena Oil-Free Acne Wash, OXY Daily Cleansing Pads, Stridex Daily Care Acne Pads, and ZapZyt Pore Treatment Gel.
Treatments to Avoid
You should be careful when choosing possible treatments for acne. Avoid any OTC products that are not proven safe and effective, such as those labeled “natural” or “ herbal.” Some products are rubbed on the skin, and others may be oral tablets, but none are proven to work. Also avoid products that claim to help acne through harsh and repeated scrubbing with rough sponges or cleaning pads. These can actually damage the skin and worsen the overall situation.
Certain Web sites sell small devices that claim to heal acne by generating light and/or heat. The user is instructed to place the hand-held device over a blemish and hold a button down for about 10 seconds, with the promise that these emissions will reduce or eliminate acne. These devices are of unknown effectiveness in treating acne. In addition, soaps and facial washes containing antibacterials such as triclocarban and triclosan have never been proven to be safe and effective for the treatment of acne.
If your acne is severe and nonprescription products do not effectively control your breakouts, referral to a dermatologist may be necessary.
REFERENCES
1. Dunn LK, O’Neill JL, Feldman SR. Acne in adolescents: quality of life, self-esteem, mood, and psychological disorders. Derm Online J. 2011;17:1.
2. Pray WS. Nonprescription Product Therapeutics. 2nd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006.
3. Acne. National Institute of Arthritis and Musculoskeletal and Skin Diseases. www.niams.nih.gov/Health_Info/
4. Imahiyerobo-Ip JI, Dinulos JG. Changing the topography of acne with topical medications. Curr Opin Ped. 2011;23:121-125.
5. Tzellos T, Zampeli V, Makrantonaki E, Zouboulis CC. Treating acne with antibiotic-resistant bacterial colonization. Expert Opin Pharmacother. 2011;12:1233-1247.
6. Ramos-e-Silva M, Carneiro SC. Acne vulgaris: review and guidelines. Dermatol Nurs. 2009;21:63-68.
7. Degitz K, Ochsendorf F. Pharmacotherapy of acne. Expert Opin Pharmacother. 2008;9:955-971.
8. Guidance for industry. Acne vulgaris: developing drugs for treatment. FDA. September 2005. www.fda.gov/downloads/Drugs/
9. FDA, HHS. Classification of benzoyl peroxide as safe and effective and revision of labeling to drug facts format; topical acne drug products for over-the-counter human use; final rule. Fed Regist. 2010;75:9767-9777.
10. FDA, HHS. Topical acne drug products for over-the-counter human use; establishment of a monograph.
Fed Regist. 1982;47:12430-12477.
11. FDA, HHS. Topical acne drug products for over-the-counter human use; tentative final monograph. Fed Regist. 1985;50:2171-2182.
12. FDA, HHS. Topical acne drug products for over-the-counter human use; amendment of tentative final monograph. Fed Regist. 1991;56:37622-37635.
13. FDA, HHS. Topical drug products containing benzoyl peroxide; required labeling; proposed rule. Fed Regist. 1995;60:9554-9558.
14. Acne. MedlinePlus. www.nlm.nih.gov/medlineplus/
15. Acne: causes. MedlinePlus. www.nlm.nih.gov/medlineplus/
16. Meixner D, Schneider S, Krause M, et al. Acne inversa. J Dtsch Dermatol Ges. 2008;6:189-196.
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