Miriam Weinstein, MD

	<bio>Dr Weinstein is an associate professor of pediatrics and medicine, University of Toronto, Ontario, and staff pediatric dermatologist, Hospital for Sick Children, Toronto. The author has no conflict of interest to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.</>

	<deck>Acne flare-ups in adolescents respond best to treatment when patients and parents understand what acne is, follow their therapy guidelines, and have reasonable expectations about what therapy can achieve. </> 

	Acne is common and often prompts the patient to seek medical advice. It classically starts in the pubertal years, although individuals with an early adrenarche may develop acne in the prepubertal years. When these changes occur markedly before puberty or are accompanied by evidence of true precocious puberty or androgen excess, a workup should be considered. This review focuses on care for the typical adolescent with acne.

	Four key pathophysiologic processes, involving the pilosebaceous unit, lead to the development of acne: 1) abnormal keratinization of the follicle, 2) sebum accumulation in the follicle, 3) active role of 

, and 4) inflammation. The pilosebaceous unit consists of a sebaceous gland attached at its opening to a hair follicle. The hair follicle opens to the surface of the skin (with or without a visible hair); follicular ostia on the face are commonly referred to as “pores.”

	Comedones, the initial lesions in acne, are hair follicles obstructed by keratinocytes and sebum, which is an oily, lipid-containing substance. When the follicular ostia are open, we refer to open comedones or “blackheads;” when the ostia are closed, the lesions are called closed comedones or “whiteheads.”

	Early development of “microcomedones” begins with disrupted shedding of keratinocytes into the follicular lumen.

 These cells are produced more rapidly than normal and are more adherent to one another, thereby blocking the follicular orifice rather than being extruded through that orifice. An increase in androgen levels,  typical during adrenarche, stimulates the sebaceous glands to produce sebum, which is secreted into the hair follicle. This secretion enables trapping of shed skin cells. When pressure builds up, the now larger comedo can rupture, allowing keratin and sebum to leak out, stimulating an inflammatory response with clinically evident papules, pustules, and nodules. Even before rupture of the comedo, inflammation plays a role as increased inflammatory cells and cytokines are evident before the disruption of epithelial turnover (Figure). Finally, 

 a gram-positive rod, inhabits the sebaceous gland and stimulates inflammation and comedo rupture through a variety of pathways.

	Many patients, parents, and physicians believe that dirt, sweat, and surface oils are the cause of acne and therefore that cleansing plays a key role in acne management. As noted above, acne is not a result of poor hygiene, and minimal evidence exists to support cleansing routines as a major intervention.

 Some cleansers have medicinal additives (eg, salicylic acid or benzoyl peroxide [BPO]), and any benefit from these cleansers is likely due to their medicinal properties and not their cleansing role. Given that many acne medications are drying or irritating, it is reasonable to direct patients to mild cleansing products.

	There is often a concern that diet plays a role in acne development. Although a large body of strong evidence is not yet available to substantiate this, some emerging data do indicate that diet may play a role. The dietary culprits include dairy products and foods with a high glycemic index, and several theories as to pathogenesis have been suggested.

 However, there are not enough data yet to suggest specific dietary changes as therapeutic interventions for acne. A well-balanced diet based on national food-selection guides (eg, My Plate, US Department of Agriculture) is the best recommendation at this time.

	Early acne develops at the center of the face (nose, chin, and forehead) in what is commonly known as the T-zone. It may spread from there to involve the cheeks and continue to spread to involve the chest and back. Not everyone develops acne in all areas. Patients also have a varying number of open or closed comedones and inflammatory lesions. Closed comedones can sometimes be difficult to identify, appearing as tiny flesh-colored papules.

	It is important to recognize healing lesions. These can present as fading red papules or macules or hyperpigmented macules (postinflammatory hyperpigmentation). Patients often believe that treatments have failed because they still see marks on their faces. They may in fact have had substantial improvement in their active acne and need to recognize that full healing takes time. It is important to recognize scars, or lesions with the potential to scar, because these indicate the need for more aggressive management options. Scars can be papular, atrophic, or keloidal. Sometimes it is very challenging to differentiate true scarring (a permanent alteration in the skin) from lesions with the potential to scar but that may still resolve. Accurate differentiation may require a referral to a dermatologist.

	Excoriations often suggest that the patient has been “picking.” Excoriating acne lesions is often a bad habit or stress-related activity; it can increase the risk of scarring and delay lesion healing. In addition, the acne will look worse and the excoriations will not necessarily respond to traditional treatments as primary lesions do. This is particularly important to point out to patients who think that they are not healing fast enough or that treatment is failing. When excoriations are extensive, there may be underlying psychological issues that need to be addressed.

	The best management plan starts with patient education. Successful therapy is much more likely when patients and parents understand what contributes to acne development, the natural history of acne, and how to properly use their medications; they also must have reasonable expectations about what therapy can achieve.

	General education should include an explanation that the degree of acne varies not only between people, but also within a patient over time. It is a chronic condition that can wax and wane, often unpredictably. Patients should understand that the goal of therapy is control of acne, not a “cure,” and that even with excellent control, some lesions are likely to appear from time to time. Therapeutic goals include reducing active lesions, preventing new lesions, and limiting scar formation.

	Educating about sun protection is important in acne patients because the retinoids and several of the oral antibiotics prescribed can make patients more sensitive to the effects of ultraviolet radiation. Many people believe that the sun makes their acne better; however, there is no good evidence that sunlight plays a role as a management strategy.

 Furthermore, the risks of such exposure outweigh the benefits.

	Several classes of medications are used for acne treatment, each with many products. The following discussion summarizes the features and roles of the different classes and selection of the correct treatment for different acne presentations.

	Retinoids are comedolytic agents (ie, they debride the plugged follicle); they can have some anti-inflammatory effects and can prevent new comedones from forming. Thus, they play an important role in treating comedonal acne and inflammatory acne, and have a maintenance role in helping to prevent new lesions. Retinoids normalize the process of keratinization and turnover of the epithelium. The 2 main topical retinoids are adapalene and tretinoin, which come in different strengths and vehicles and are available as single agents or as combination products with antibiotics or BPO (Table 1).

	Tazarotene is a potent topical retinoid for more significant acne, and isotretinoin is an oral retinoid indicated for severe or scarring acne. Isotretinoin requires referral to a dermatologist, and its use is not discussed here. Pediatricians should become comfortable using topical retinoids because they form a major part of the therapy for acne. Yentzer and colleagues found that dermatologists prescribed topical retinoids considerably more frequently than pediatricians.

	Topical retinoids are useful for removing comedones and helping to prevent new flareups and also have some anti-inflammatory properties. Because acne is a chronic and recurrent condition, it is reasonable to consider keeping patients on retinoids for longer-term maintenance between flares.

 Retinoids can cause xerosis, irritation of the skin, and even irritant dermatitis. They also make patients more sensitive to the effects of ultraviolet radiation. Patients with dry or atopic skin or those poorly tolerant to the irritating effects would do better with a milder strength or cream rather than a gel-based product.

	Another strategy to improve tolerance is to use retinoids every second or third night, with an increase to nightly use if tolerated. Patients should be advised to refrain from laser therapy, waxing for hair removal, and exfoliating in treated areas because this can increase the risk of irritation or tissue injury. Because retinoids are teratogenic, their use (even topical) should be avoided during pregnancy. Tretinoin can be unstable with ultraviolet radiation exposure and thus should be applied at bedtime. Often a retinoid will cause acne lesions to become more prominent after initiation of therapy, and patients must be advised of this.

	These agents include topical BPO and topical and oral antibiotics. All these products reduce 

 and also directly reduce inflammation. BPO has an advantage because it does not seem to induce bacterial resistance in the way the antibiotics can. Therefore, even if BPO would not be enough as a single therapy for substantial acne, it should be considered as an adjunct when antibiotics are used. Several products on the market combine a topical antibiotic and BPO. BPO is also available as over-the-counter washes and leave-on products that can be incorporated into a management routine. Rarely, patients can develop an allergic contact dermatitis to BPO and therefore should not use it. Patients should be warned that BPO can bleach fabrics.

	Topical antibiotics typically include erythromycin, clindamycin, sodium sulfacetamide, and the newer topical dapsone. These are good treatments for mild-to-moderate inflammatory acne and, as mentioned above, clinicians should strongly consider adding BPO to the regimen either as a combination product or a separate product. Clindamycin and erythromycin are available in combination products with BPO (Table 1). Topical dapsone, used twice daily, is well tolerated and has good clinical efficacy.

 It does not appear to be a problem for patients with G6PD deficiency. Topical dapsone should be applied at a separate time from BPO (and after all BPO is removed) because the 2 products together may lead to a benign but undesirable discoloration of the skin.

	Oral antibiotics are usually reserved for moderate acne, often after a trial of topical therapy has failed (Table 2). The tetracycline-based antibiotics are the classic treatments for acne. Tetracycline works well for acne, but because it cannot be taken with food, this often leads to compliance problems or poor absorption. Minocycline is widely used and sometimes considered superior to other acne treatments; however, this belief is not supported by a recent Cochrane review.

 In addition to showing the same types of adverse effects as are possible with all tetracyclines, such as pseudotumor cerebri, gastrointestinal upset, and photosensitivity, minocycline has been associated with dyspigmentation of the skin and lupus-like reactions in rare cases.

 Doxycycline is also used for acne. Because tetracyclines can stain the teeth, they are usually avoided in children aged younger than 9 years. For younger children requiring oral therapy, the macrolide antibiotics such as erythromycin have been used. A variety of other antibiotics (eg, trimethoprim, azithromycin) have been used to treat the inflammatory components of acne.

 is a concern because antibiotics are often used chronically or repeatedly, and resistance may manifest as treatment failures.

 Of more ominous concern are data suggesting that antibiotics can change the resistance patterns in 

 Because the tetracyclines and trimethoprim, both used for acne, are also used for methicillin-resistant 

, it is important to avoid creating antibiotic resistance to pathogenic organisms while chronically treating acne. Treatment strategies to help prevent this include limiting monotherapy with antibiotics, considering retinoids instead for maintenance therapy, using BPO in therapeutic routines, and avoiding prolonged courses of oral antibiotics.

	Oral contraceptives (OCs) have been used for acne and may be a good choice for females who experience perimenstrual flares or those with features of polycystic ovary syndrome. Estrogen may act by inhibiting androgen production at the gonadal level or by blocking the effects of androgens at the sebaceous glands.

 There is no clear superiority of 1 OC over another, and treatment trials are often needed to assess relative benefits and adverse effects. Therapy must be continued for several months before assessing therapeutic effect. Some OCs are labeled with an indication for acne, but even those not marketed for acne may have some off-label benefit. Patients should receive the standard counseling about the risks and benefits of OC use. Antiandrogen therapies are sometimes used, but are outside the scope of this review and are not typical of adolescent acne management.

	Azelaic acid helps regulate the disordered keratinization of the follicular unit, aiding in comedonal control, and also inhibits 

 thereby reducing some of the inflammation. It is typically applied twice daily.

	Salicylic acid is available in over-the-counter preparations. This agent is comedolytic, can be mildly anti-inflammatory, and acts to “dry up” active lesions. Because it is drying and can cause irritation, caution should be used if retinoids are also prescribed.

	Pediatricians can play an important role in managing mild-to-moderate acne. (Table 3) describes the appropriate first-line therapies.

	Mild acne is usually treated with topical therapy. Topical products are available in various vehicles. Gels and solutions are less likely to have a greasy feeling on the skin but may be too drying or irritating for patients with dry or atopic skin. Creams are more moisturizing and may be good choices for patients with dry skin or those easily irritated, but may feel too greasy for some patients, especially those with very oily skin.

	Patients with primarily comedonal acne benefit from starting with a topical retinoid, although adding an anti-inflammatory product helps reduce the inflammation that may occur during initial retinoid therapy. Patients with mostly inflammatory acne should use topical antibiotics and topical BPO to treat active lesions, but would also benefit from adding a retinoid to this regimen to help with longer-term control of new comedones. Combination products allow expansion of therapy while using only 1 or 2 topical products; however, there is no product that contains all 3 agents: BPO, a retinoid, and an antibiotic. Many patients will be compliant with use of only 1 product per day, and selecting the product that best fits the morphology of their acne would be a good starting place.

	It is important to educate patients on how to apply topical therapy. The medication must be applied to the area or “field” where acne is occurring, and not just on the individual lesions. A thin layer applied to this area is usually sufficient. Patients often need 6 to 12 weeks of continuous therapy before assessing the benefit. This is longer than many patients will continue treatment unless they have physician guidance.

	If a patient’s acne fails to respond to first-line therapy, it is important to ensure that the patient complied with the use of the medication as intended. If the patient was compliant, then a switch to a different product or a different class of medication is warranted. 

	Patients with moderate acne may still benefit from topical therapy and can be offered this choice. However, oral therapy is often needed. Oral antibiotics are a good choice, but it is still useful to add a topical retinoid to address any comedones and help prevent new lesions, and it is suggested to use topical BPO (as a wash or a leave-on product) to reduce bacterial resistance from the oral therapy. Some patients resist using topical therapy while they are also taking oral therapy. Physicians should highlight why multimodal therapy is preferred. Usually 4 to 12 weeks of treatment for moderate acne are needed to assess success. Ideally, the patient would be maintained on topical therapy, and an oral antibiotic would be reinstituted when flare-ups are no longer controlled by topical therapy. This strategy is preferable to chronic, long-term antibiotic use. Some patients may experience flare-ups shortly after discontinuing oral antibiotics and may need them frequently; it might be reasonable to refer these cases to a dermatologist to consider isotretinoin.

	Females with premenstrual flares, those who have failed oral antibiotics, or those who desire OCs for other reasons can consider hormonal therapy. Hormonal therapy can be used in conjunction with topical retinoids, BPO, or even with oral antibiotics. Often a longer course (at least 3 months) is needed to assess the benefits from OCs.

	Patients with unyielding acne or scars, scarring potential, or deep nodulocystic acne should be referred to a dermatologist.

	Chemical peels and intralesional steroids applied to deep lesions are examples of adjunctive therapies sometimes used by dermatologists. A variety of techniques are available to improve scars caused by acne, such as laser treatments, filler injections, and small surgical procedures. Referral to a cosmetic dermatologist or plastic surgeon is suggested.

	Most acne can be well controlled. Patient education is key because success is more likely when patients have a good understanding of why their acne occurs, the natural history of acne, the proper use of medications, and reasonable expectations of therapy. Selecting the correct treatment is an art that must address lesion morphology, extent of acne, patient preference regarding product choice and application, adverse-effect profile, and motivation of the patient to engage in therapy.

	A wide variety of topical and oral therapies exist, so pediatricians can tailor the treatment regimen to the principles of acne therapy and the individual needs of the patient. Reevaluation and reeducation over time, and modifying the treatment if necessary, will ensure the most successful outcomes.

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Acne flare-ups in adolescents respond best to treatment when patients and parents understand what acne is, follow their therapy guidelines, and have reasonable expectations about what therapy can achieve.

Miriam Weinstein, MD

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