Managing Adolescent Acne : A Guide for Pediatricians ...€¦ · 3. Design an appropriate treatment...

DOI: 10.1542/pir.26-7-2502005;26;250Pediatrics in Review

Daniel P. KrowchukManaging Adolescent Acne : A Guide for Pediatricians

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Managing Adolescent Acne:A Guide for PediatriciansDaniel P. Krowchuk, MD*

Author Disclosure

Dr Krowchuk did not

disclose any financial

relationships relevant

to this article.

Objectives After completing this article, readers should be able to:

1. Review the epidemiology and causes of adolescent acne.2. Recognize the types of acne lesions and assess the severity of acne.3. Design an appropriate treatment plan for adolescents who have acne.4. Discuss the indications for use and adverse effects of topical and systemic agents

employed in acne therapy.

IntroductionAcne vulgaris, known simply as “acne,” is a chronic condition that may last for years andcause emotional distress and permanent scarring. Although acne has no cure, medicationscan control the disease and limit or prevent scar formation.

EpidemiologyAcne is the skin disease most commonly treated by physicians. It is estimated that17 million Americans have acne, including 85% of adolescents ages 15 to 17 years. In 2000,the most recent year for which data are available, there were an estimated 14.5 million visitsto physicians made by adolescents for acne treatment.

Adolescent acne correlates best with pubertal stage, although lesions may becomeevident before secondary sexual characteristics appear. Early in puberty, blackheads andwhiteheads predominate, and the midface (midforehead, nose, and chin) typically isinvolved. Later, inflammatory lesions become more prevalent, and the lateral cheeks, lowerjaw, back, and chest are affected.

PathogenesisAcne is a disorder of the pilosebaceous unit, comprised of a follicle or pore, sebaceousgland, and rudimentary or vellus hair. These specialized follicles are concentrated on theface, chest, and back, which explains why acne occurs in these areas. Although thepathogenesis of acne has not been defined, clearly multiple factors contribute (Fig. 1).Designing appropriate treatment requires an understanding of these factors.

Hormones and Sebum ProductionAndrogens play an integral role in causing acne. At age 8 or 9 years, prior to the appearanceof secondary sexual characteristics, adrenarche results in increased adrenal production ofdehydroepiandrosterone sulfate (DHEAS). Rising levels of DHEAS, perhaps after conver-sion to more potent androgens such as testosterone and dihydrotestosterone, causesebaceous glands to enlarge and produce more sebum. Sebum secretion peaks duringadolescence and declines after age 20 years. In general, acne severity correlates with the rateof sebum secretion. Of note, sebum from patients who have acne is deficient in linoleicacid, a factor that may alter the keratinization process and contribute to follicularobstruction.

Despite the importance of androgens in causing acne, most males have normal hor-mone levels. For females, the picture is more complex: Hormone levels usually are normal,but free testosterone and DHEAS concentrations may be elevated, and sex hormone-binding globulin (SHBG) may be reduced.

*Departments of Pediatrics and Dermatology, Wake Forest University School of Medicine and Brenner Children’s Hospital,Winston-Salem, NC.

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250 Pediatrics in Review Vol.26 No.7 July 2005



BacteriaPropionibacterium acnes is an anaerobic, gram-positivediphtheroid that colonizes pilosebaceous follicles follow-ing increases in sebum production. Although P acnes is anormal inhabitant of the skin, its numbers are higher inpatients who have acne than in those who are unaffected.P acnes produces chemoattractant factors that causepolymorphonuclear neutrophils (PMNs) to enter pilose-baceous follicles. As PMNs ingest P acnes, hydrolyticenzymes are released that damage the follicle wall. Fol-licular contents then enter the surrounding tissue, wherethey incite inflammatory reactions that are manifestedclinically as erythematous papules, pustules, or nodules.P acnes also produces lipases that hydrolyze triglyceridesto free fatty acids (FFA), a factor that may contribute tothe inflammatory process and follicular obstruction.

Abnormal KeratinizationIn acne, epithelial cells lining the follicle are not shedproperly and become more cohesive. The result is acollection of cells and sebum that accumulates within thefollicle. Termed “comedogenesis,” this process is centralto the development of acne lesions. Although the triggerfor comedogenesis has not been identified, proliferationor adhesion of keratinocytes, cytokine production, andthe effects of androgens may be responsible.

GeneticsFamilial trends are well recognized in patients who haveacne, but an exact pattern of inheritance has not beendefined. Because the disease is common and modified byexternal factors, it is not possible to predict the severity ofdisease in an individual patient based on family history.

Clinical ManifestationsThe pathologic processes previously described have clin-ical correlates. Patients who have acne may exhibit ob-structive or inflammatory lesions, scars, or cysts.

Obstructive Lesions (Comedones)Obstruction within the follicle initially is microscopic;such lesions are termed microcomedones. As comedonesenlarge, they become apparent clinically as open come-dones (blackheads) or closed comedones (whiteheads).Open comedones represent follicles that have widelydilated orifices (Fig. 2). The black color of these lesionsdoes not represent dirt; rather, it may result from oxida-tion of melanin, interference with transmission of light

Figure 1. Pathogenesis of acne.

Figure 2. Open comedones in the external ear and on the face.Reprinted from Krowchuk DP, Lucky AW. Managing adoles-cent acne. Adolesc Med. 2002;12:355–374 with permissionof Hanley & Belfus.

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Pediatrics in Review Vol.26 No.7 July 2005 251



through compacted epithelial cells, or the presence ofcertain lipids in sebum. Closed comedones are smallwhite papules that have no surrounding erythema (Fig.3). They represent follicles that have become dilated withcellular and lipid debris but possess only a microscopicopening to the skin surface.

Inflammatory LesionsInflammatory acne is characterized by erythematous pap-ules, pustules, or nodules. Papules and pustules are small,measuring less than 5 mm in diameter (Fig. 4). Nodulesmeasure more than 5 mm in diameter and often involvemore than one follicle. As inflammatory lesions resolve,erythematous or hyperpigmented macules may remainfor as long as 12 months; these often are mistaken forscars.

ScarsSome patients who have acne develop scars as inflamma-tory lesions resolve. In general, scarring is most likely inpatients who have large papules or nodules. On the face,acne scars appear as small pits; on the trunk, they usuallyare small hypopigmented spots. Rarely, patients develophypertrophic or keloidal scars. Because scars may beirreversible, their presence should prompt the clinician tobe aggressive in the selection of therapeutic agents activeagainst the inflammatory component of the disease. Truecysts, compressible nodules that lack overlying inflamma-tion, also may be observed in patients who have acne.

EvaluationThe first step in evaluation is to gather a history. Somehelpful questions and their rationale are presented inTable 1. The physical examination should include the

skin of the face, chest, and back. Examination of othersystems is dictated by findings from the history. Tofacilitate later comparison, a diagram of the face (Fig. 5)can be used to record the approximate number of inflam-matory lesions and open and closed comedones. Theclinician also can estimate the numbers and types oflesions present on the back and chest. This process can beaccomplished quickly and provides an objective methodof monitoring the patient’s progress. In addition to thislesion count, it is helpful to make a global assessment ofacne severity (eg, mild [Fig. 6], moderate [Fig. 7], orsevere [Fig. 8]) that represents a synthesis of the number,size, and extent of lesions as well as the presence ofscarring (Table 2).

Differential DiagnosisConditions that may mimic adolescent acne are pre-sented in Table 3.

Figure 3. Closed comedones, small white papules withoutsurrounding erythema, located on the forehead.

Figure 4. Inflammatory papules and pustules located on theback of a patient who has severe acne. Reprinted fromKrowchuk DP, Lucky AW. Managing adolescent acne. AdolescMed. 2001;12:355–374 with permission of Hanley & Belfus.

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Laboratory FindingsLaboratory evaluation (eg, measurement of free testos-terone, DHEAS, 17-hydroxyprogesterone) should bereserved for females who have early- or late-onset acne,acne associated with other evidence of androgen excess(eg, irregular menses, hirsutism, alopecia, or clitoro-megaly), or acne unresponsive to conventional therapy.

ManagementThe successful management of acne depends on an un-derstanding of the types of lesions present, the severity ofdisease, and the mechanism of action and possible ad-verse effects of available medications. Although there isno standardized treatment plan, rational guidelines exist(Table 4). Realistic goals of treatment are to reduce thenumber and severity of lesions and prevent scarring.

Patient EducationThe first step in management is to describe briefly thecauses of acne and attempt to dispel commonly heldmyths:

! Acne is not caused by dirt, and frequent washing willnot improve the condition. In fact, frequent washingor the use of harsh soaps may irritate the skin and limita patient’s tolerance for topical medications. To con-trol oily skin, patients may be advised to wash once ortwice daily using a mild nondrying soap or cleanser.

! For most adolescents, diet plays no role in acne. Occa-sionally, a patient may observe an apparent relationshipbetween a particular food and a flare-up. In such in-stances, common sense dictates limiting the intake ofthis food.

Table 1. Key Elements of the Acne History*Question Rationale

For all patientsHow long has the patient had acne? When did it begin? Early- or late-onset acne may indicate androgen excess.Which medications have been tried? Which medications have been successful; which have not?

Did treatment failures result from improper technique orinsufficient duration of use?

Did adverse effects occur?Is the patient using other products to treat acne? Many nonprescription acne preparations (eg, abrasive soaps) are

irritating and may limit the patient’s ability to tolerate moreeffective therapies.

Is the patient receiving other medications? Topical or oral corticosteroids (including anabolic-androgenicsteroids) may cause acne lesions.

Lithium, isoniazid, hydantoin, and rifampin may worsen acne.Does the patient use cosmetics or hair greases? Cosmetics containing lanolin or oil or hair greases may cause or

worsen acne.Does the patient have recreational or occupational

activities that may worsen acne?Pressure applied by helmets, chin straps, shoulder pads, or tight

occlusive garments may worsen acne.Oils or greases inadvertently applied to the skin as part of one’s

occupation can cause obstructive lesions.Is there a history of other medical problems? Adolescents who have a history of atopic dermatitis or those

who report “sensitive” skin may not tolerate topicalmedications that dry or irritate skin.

For femalesIs the patient menstruating?Are there premenstrual flares?

Premenstrual flares are common in women who have acne.

Is there a history of oligomenorrhea or hirsutism? The presence of oligomenorrhea or hirsutism, coupled with thepresence of acne, may suggest androgen excess caused bypolycystic ovarian disease or late-onset congenital adrenalhyperplasia.

Is the patient sexually active? Patients who are sexually active require effective contraceptionduring treatment with isotretinoin.

Does the patient use hormonal contraception? Certain hormonal contraceptives may worsen acne (see text).Women using oral contraceptives may require a secondary form

of contraception if oral antibiotics are being used to treatacne (see text).

*Adapted from Krowchuk DP, Lucky AW. Managing adolescent acne. Adolesc Med. 2001;12:355–374

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The patient should be counseled about factors thatmay worsen acne. The information contained in Table 1may help guide this discussion:

! Picking at, wearing athletic gear over, or otherwisetraumatizing acne lesions may increase inflammation,prolong resolution of lesions, and increase the likeli-hood of scar formation.

! Cosmetics, sunscreens, and moisturizers, particularlythose containing oils, may worsen acne. Advise theadolescent to select products that are labeled non-comedogenic or nonacnegenic.

! A variant of cosmetic acne, known as pomade acne(Fig. 9), may occur when greases used to style hair areapplied inadvertently to the skin. Pomade acne occursalmost exclusively in African-Americans and is charac-terized by the presence of comedones located on theforehead and temporal areas. To prevent such lesions,patients can be advised to avoid placing hair care prod-ucts on the skin.

! Young women often experience premenstrual exacer-bations that may be caused by androgenic effects ofprogesterone, which is dominant during the secondhalf of the menstrual cycle.

! Environmental factors may exacerbate acne amongyoung people who come into contact with grease atwork. Despite this, patients may be unwilling or unableto alter employment to accommodate concerns aboutacne.

Patients should be advised that acne treatment is along-term process; often 6 to 8 weeks or longer arerequired to see improvement. Additionally, once lesionsresolve, treatment may need to be continued until it isclear that new lesions are not appearing.

Topical TherapiesCommonly employed topical preparations include ben-zoyl peroxide, antibiotics, retinoids, and salicylic acid.

BENZOYL PEROXIDE. Benzoyl peroxide (BP) primarilyhas an antibacterial effect and is useful in controlling

Figure 5. In each region, the physician records the number ofopen comedones (OC), closed comedones (CC), and inflamma-tory lesions (IL). Redrawn with permission from Merck & Co.The original appeared in Lucky AW, et al. A multiratervalidation study to assess the reliability of acne lesion count-ing. J Am Acad Dermatol. 1966;35:559–565 and was usedwith permission of Elsevier Science.

Figure 6. Mild acne. A few small inflammatory lesions arepresent. Reprinted from Krowchuk DP, Lucky AW. Managingadolescent acne. Adolesc Med. 2001;12:355–374 with per-mission of Hanley & Belfus.

Figure 7. Moderate acne. Many inflammatory lesions arepresent. Reprinted from Krowchuk DP, Lucky AW. Managingadolescent acne. Adolesc Med. 2001;12:355–374 with per-mission of Hanley & Belfus.

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inflammatory acne. It also may decrease the formation ofFFA, thereby improving obstructive (comedonal) dis-ease. These two actions make it an excellent drug in themanagement of patients who have mild inflammatory ormixed (eg, inflammatory and comedonal) acne. BecauseBP also prevents the emergence of antibiotic resistanceamong P acnes, it may be used adjunctively for patientsreceiving long-term oral or topical antibiotic therapy.

BP is available with or without a prescription in con-centrations ranging from 2.5% to 10%. Over-the-counterproducts include creams, lotions, washes, and gels. Pre-scription forms generally employ a gel vehicle, a factorthat enhances efficacy. A single daily application of aproduct containing a 5% concentra-tion is adequate for most patients.Increasing the concentration to10% does not enhance the thera-peutic effect greatly, but does in-crease the likelihood of drying, ery-thema, and burning. BP usually isapplied once daily, although twice-daily use may be beneficial for somepatients.

As with all topical medications,BP is applied as a thin coat to allacne-prone areas rather than to in-dividual lesions. When the entireface is to be treated, the patient may

be instructed to dispense an amount the size of a peaonto a finger tip. To distribute the medication, the fingeris touched to each side of the forehead, each cheek, andthe chin. The medication then is spread to cover theentire face, avoiding areas prone to irritation, such as thecorners of the eyes, the alar folds, and the angles of themouth. To treat larger areas, such as the back or chest, aBP wash applied during a bath or shower may be used,although greater efficacy may be achieved by applyingthe gel formulation and allowing it to remain in place forseveral hours (eg, overnight).

Adverse reactions associated with BP use includestinging after application and drying, redness, and peel-ing of the skin. These reactions may be prevented orlimited by selecting an emollient or water-based gel,reducing the concentration of BP, or decreasing thefrequency of application. Contact dermatitis is an un-usual complication characterized by erythema, small pap-ules, and pruritus. Patients should be advised that BPmay bleach clothing and bedding. It is classified as preg-nancy category C by the United States Food and DrugAdministration (FDA), meaning that risk to the fetuscannot be ruled out.

TOPICAL ANTIBIOTICS. Topical antibiotics reduce con-centrations of P acnes, inflammatory mediators, and pos-sibly, FFA. As a result, these agents are most useful intreating mild-to-moderate inflammatory acne. The prac-tical difficulties and cost associated with applying topicalantibiotics to large areas limit their use to patients whohave facial acne. In the United States, products contain-ing clindamycin or erythromycin are available and havecomparable efficacy. However, concerns about antibioticresistance limit their use. Sodium sulfacetamide, with orwithout sulfur, also is available. Topical antibiotics are

Figure 8. Severe acne. Numerous large inflammatory lesionsand scarring are present. Reprinted from Krowchuk DP, LuckyAW. Managing adolescent acne. Adolesc Med. 2001;12:355–374 with permission of Hanley & Belfus.

Table 2. Grading Scale for Severity of Facial Acne*Severity Clinical Characteristics

Mild —About one fourth of the face is involved—There are few to several papules or pustules, but no nodules

or scarringModerate —About one half of the face is involved

—There are several to many papules or pustules and a few toseveral nodules. A few scars may be present

Severe —Three quarters or more of the face is involved—There are many papules and pustules and many nodules.

Scarring often is present

*Adapted from Pochi PE, Shalita AR, Strauss JS, et al. Report of the consensus conference on acneclassification. J Am Acad Dermatol. 1991;24:495–500 and Allen BS, Smith JG. Various parameters forgrading acne vulgaris. Arch Dermatol. 1982;118:23–25.

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available in a variety of vehicles. As with other topicalagents, lotions and creams are less drying than solutionsor gels.

Products that combine agents enhance the therapeu-tic effect. For example, combinations of BP 5% andclindamycin or erythromycin are more effective thaneither drug alone. Beyond this, the inclusion of BP alsoprevents the development of antibiotic resistance. Theprimary disadvantage of combination preparations is thesignificantly greater cost. If cost is an issue, some clini-cians provide separate prescriptions for the generic formsof BP and clindamycin and advise patients to apply themedications simultaneously.

An area of concern related to the use of topical orsystemic antibiotics is the emergence of resistant forms ofP acnes. Between 1991 and 1996, the percent of patientsattending a dermatology clinic in the United Kingdomcarrying antibiotic-resistant organisms rose from 34.5%to 60%. In 1996, 47%, 41%, and 26% of these patientsharbored strains of P acnes that were resistant to eryth-romycin, clindamycin, or tetracycline, respectively. Themajority of strains resistant to erythromycin exhibitedcross-resistance to clindamycin and other macrolide an-tibiotics. Multiple drug resistance was observed in 18% of

isolates. Among propionibacteria resistant to tetracy-clines, the degree of resistance to tetracycline is greaterthan that to doxycycline, which exceeds that to minocy-cline. An association between carriage of erythromycin-resistant propionibacteria and poor clinical response tooral treatment with this agent has been demonstrated.With this issue in mind, some clinicians do not prescribeoral erythromycin for acne or they use it only for previ-ously untreated patients who are unlikely to harbor resis-tant organisms. Similarly, the use of topical erythromycinor clindamycin as monotherapy (ie, not combined withbenzoyl peroxide) may be ineffective due to bacterialresistance.

TOPICAL RETINOIDS. Patients who have numerousblackheads and whiteheads will benefit from a topicalretinoid. These agents normalize the keratinization pro-cess within follicles and reduce obstruction and the riskfor follicular rupture. Tretinoin is the best known topicalretinoid and is available in creams (0.025%, 0.05%,0.1%), gels (0.01%, 0.025%), and a liquid (0.05%). Thevehicle affects efficacy; creams are less potent than gels,which are less potent than the liquid. Newer formula-tions appear to be as effective but less irritating than

Table 3. Some Conditions That May Mimic Adolescent AcneCondition Description Differentiating Features

Adenoma sebaceum Erythematous papules or nodules that appear inthe nasolabial folds or on the cheeks ofindividuals who have tuberous sclerosis.

Lesions often appear during childhood(earlier than the lesions of acne);comedones are absent.

Acne rosacea Erythematous papules, pustules, and scaling thatinvolve the central face.

Typically occurs in adults; comedones areabsent.

Gram-negativefolliculitis

Sudden appearance of papules, pustules, andnodules in a patient being treated with oralantibiotics for acne.

Sudden worsening of acne in a patient whohas been receiving long-term antibiotictreatment for acne vulgaris.

Keratosis pilaris Small, rough-feeling, skin-colored orerythematous papules centered about follicles.A keratin plug emerging from the follicularorifice can be observed or palpated.

The presence of a central keratin plugdifferentiates keratosis pilaris from acne.Lesions also may be located on the upperouter arms, thighs, or buttocks.

Pityrosporumfolliculitis

Erythematous papules and pustules that occuron the chest, shoulders, and upper back.

Lesions spare the face; a potassiumhydroxide preparation performed on apustule roof demonstrates budding yeast.

Steroid acne Dome-shaped erythematous papules appearingon the face and trunk weeks after systemiccorticosteroids have been begun.

Lesions have a monomorphous appearance(eg, only papules without comedones).There is a temporal relationship betweenthe onset or worsening of acne andcorticosteroid therapy.

Steroid rosacea Erythematous papules or pustules that appeararound the mouth and eyes. Often occurs inindividuals who have applied potent topicalcorticosteroids to the face or have usedinhaled corticosteroids.

Lesions are concentrated around the mouth(or eyes), and comedones are absent.

dermatology acne




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traditional varieties. Tretinoin also is available in genericform.

Adolescents who use tretinoin often experience irrita-tion, redness, or dryness. For persons of color, thisinflammation may result in hypo- or hyperpigmentationthat can persist for months. To prevent or limit adverseeffects, therapy often is begun with a low-strength prep-aration (eg, tretinoin cream 0.025%). Patients should beadvised to dispense a small amount (a pea-sized dab issufficient to cover the entire face) and to apply themedication every third night, progressing as toleratedover 2 to 3 weeks to nightly application. Tretinoin maycause an apparent temporary worsening of acne 2 to3 weeks after treatment has begun and increased sensi-tivity to sunlight likely caused by skin irritation.

Because tretinoin is nearly identical in chemical struc-ture to isotretinoin, some have raised concern aboutpotential teratogenicity. However, there have been noreports of malformations occurring in infants born towomen who used tretinoin during pregnancy. Neverthe-less, tretinoin is classified as pregnancy category C, andfor this reason, its use is avoided during pregnancy.Because BP inactivates tretinoin, the two drugs shouldnot be applied simultaneously. Rather, BP may be ap-plied in the morning and tretinoin at night.

Other retinoids also are available. Adapalene in a 0.1%gel formulation has been shown to be as effective astretinoin gel 0.025% but less irritating. It is available as a0.1% alcohol-free gel, cream, and solution or as pledgets.The principles of use and potential adverse effects areanalogous to those of tretinoin. Like tretinoin, it isclassified as pregnancy category C. Tazarotene is formu-lated in 0.05% and 0.1% gels and creams. Althoughproven effective in clinical studies, it is much more ex-pensive and may be more irritating than other retinoids,and due to concerns about teratogenicity, it is contrain-

dicated in pregnancy. For these reasons, it is not pre-scribed widely for the treatment of acne.

SALICYLIC ACID. Salicylic acid reduces the formationof obstructive lesions; it is less effective than topicalretinoids but less irritating. It is useful in the manage-ment of obstructive acne involving the face for patientswho cannot tolerate retinoids or in the treatment ofcomedones on the trunk (where it may be impracticaland too costly to apply a retinoid).

AZELAIC ACID. Azelaic acid 20% is both antibacterialand anticomedonal. It is applied twice daily and appearsto be well tolerated, although some patients experiencepruritus, burning, stinging, tingling, or erythema. Nosystemic toxicity has been reported. In one controlledtrial, azelaic acid was as effective as BP 5%, tretinoin0.05%, or erythromycin 2%. It is an alternative for pa-tients who have mild-to-moderate inflammatory andcomedonal acne or for those who have obstructive le-sions who cannot tolerate tretinoin.

Systemic TherapiesORAL ANTIBIOTICS. Oral antibiotics possess greater

efficacy than topical preparations; thus, they are pre-scribed for patients who have moderate-to-severe acne orinflammatory disease involving the trunk as well as theface. They exert their anti-inflammatory effect by de-creasing bacterial colonization and inhibiting neutrophilchemotaxis; they also reduce the concentration of FFA insebum.

Tetracycline and erythromycin are the oral antibioticsprescribed most often for the treatment of acne; bothhave been proven effective and are inexpensive. How-ever, as discussed previously, bacterial resistance to eryth-romycin may limit its usefulness. Depending on diseaseseverity and the patient’s weight, each is initiated at adose of 250 to 500 mg twice daily, although the higherdose usually is favored. Both are available in liquid formfor patients who cannot swallow pills or capsules. Tetra-cycline may cause gastrointestinal disturbances. To as-sure absorption, it should not be taken with milk or otherdairy products and should be taken on an empty stomach(eg, 30 min before or 2 h after a meal). Tetracyclineshould not be used during pregnancy or for patientsyounger than 9 years of age due to potential discolora-tion of teeth. Because tetracycline occasionally hascaused esophageal ulceration, patients should be advisedto take the medication with a large glass of water and toavoid reclining immediately after ingesting a dose. Otheradverse effects include photosensitivity, vulvovaginal

Figure 9. Pomade acne, characterized by multiple closedcomedones on the forehead

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candidiasis, and uncommonly, pseudotumor cerebri,hyperpigmentation, and onycholysis. The primary ad-verse effect of erythromycin is gastrointestinal upset thatmay be avoided by taking the medication with food.

For those who fail to respond to or cannot toleratetetracycline or erythromycin, doxycycline often is effec-tive. It is begun at a dose of 50 to 100 mg twice daily andcan be taken with food. Unfortunately, doxycycline iseven more likely than tetracycline to induce photosensi-tivity reactions. An alternative to doxycycline is minocy-cline, which is considered highly effective, particularlywhen P acnes resistance is suspected. Minocycline isinitiated at a dose of 50 to 100 mg bid; the latter dose isrecommended when patients are suspected of harboringtetracycline-resistant propionibacteria. It is more expen-sive than other antibiotics and has uncommon but sig-nificant adverse effects, including pigmentation of theskin, teeth, or mucosa or autoimmune syndromes (eg, aserum sickness-like reaction, a hypersensitivity syn-drome, lupus erythematosus-like reaction, and hepatitis).Several other oral antibiotics have been used in thetreatment of acne but have not been studied well, includ-ing ampicillin, amoxicillin, cephalexin, and trimethoprim-sulfamethoxazole.

As with other acne therapies, 6 to 8 weeks often arerequired before oral antibiotics produce a significantclinical effect. Once the appearance of new lesions hasceased or been reduced satisfactorily, the dose may betapered gradually or withdrawn.

Concern often is raised that oral antibiotics may di-minish oral contraceptive efficacy by decreasing entero-hepatic recirculation of contraceptive steroids, enhanc-ing their hepatic degradation, or increasing their renal orfecal excretion. Research fails to support a systematicinteraction between antibiotics used to treat acne (eg,tetracyclines or ampicillin) and oral contraceptives.However, it is possible that occasional oral contraceptiveusers experience declines in plasma ethinyl estradiol andprogestin concentrations during antibiotic treatmentthat could reduce contraceptive efficacy. Although thisrisk is very low, the Council on Scientific Affairs of theAmerican Medical Association concluded that the useof an additional nonhormonal method of contracep-tion or alternate contraceptive method be considered forwomen receiving long-term antibiotic therapy, particu-larly if they experience diarrhea or breakthrough bleed-ing. Clinicians should counsel patients about this con-cern, although the issue may be moot for adolescentsbecause those using hormonal contraception are advisedroutinely to use a condom during all sexual encounters toprotect against sexually transmitted infections.

ISOTRETINOIN. Isotretinoin is an oral analog of vita-min A that is highly effective for the treatment of severerecalcitrant acne. Despite its efficacy, oral isotretinointherapy may be associated with important adverse reac-tions, the most serious of which is teratogenicity. For thisreason, the drug should be prescribed only by physicianswho have experience in its use. Presently, all isotretinoinprescriptions require that a qualification sticker be af-fixed. To obtain these stickers, physicians must have readeducational materials provided by the manufacturer andsigned a letter of understanding regarding isotretinoinuse and its potential adverse effects on a fetus. Informedconsent is required of all patients for whom isotretinoin isbeing prescribed.

Reports to the FDA have raised concern that isotre-tinoin use, through mechanisms unknown, may pre-dispose patients to the development of depression orsuicide. Although an association has not been demon-strated, clinicians caring for patients who are receivingisotretinoin should remain alert to the presence or devel-opment of mental health disorders, including depressionand suicidal ideation.

HORMONAL THERAPY. Combined oral hormonalcontraceptives (OCs), those containing an estrogen andprogestin, may improve acne. Estrogen increases SHBGthat, in turn, decreases biologically active free testoster-one. OCs also suppress gonadotropin secretion, therebyreducing ovarian androgen production. Recent placebo-controlled trials document that OCs containing ethinylestradiol (35 mcg) and the progestin norgestimate orethinyl estradiol (20 mcg) and levonorgestrel improveacne. It is likely, however, that other OCs also have abeneficial impact on acne. Despite this, these agents arenot viewed as primary therapy for acne but as an adjunctto standard medications.

Acne may be exacerbated by endocrine disorders suchas polycystic ovarian syndrome or the metabolic syn-drome (ie, insulin resistance, obesity, hypertension, anddyslipidemia). Use of long-acting progestin implants ordepot medroxyprogesterone acetate may be associatedwith worsening acne.

Complementary and Alternative TherapiesA number of complementary and alternative therapieshave been advocated for the treatment of acne, butefficacy and safety have not been established for most.One agent that has received attention is tea tree oil, amixture of terpenes and related alcohols that has antibi-otic and antifungal properties. In a single-blind trial of124 patients who had mild-to-moderate acne, a 5%

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water-based gel formulation of tea tree oil was as effectiveas BP 5% water-based lotion. Although considered safewhen used topically, it may cause contact dermatitis and,if applied undiluted, may induce comedogenesis. Inyoung children, inadvertent ingestion of small amountsof tea tree oil has produced confusion, ataxia, and drows-iness.

Guggul (derived from the resin of the tree Commi-phora mukul) was compared with tetracycline in patientswho had inflammatory acne. After 3 months of therapy,patients in both groups experienced similar reductions inthe numbers of lesions.

Therapies that have been employed and that are be-lieved to be safe (but of unproven efficacy) include aloevera (for acne scars), witch hazel (used as an astringent),calendula (marigold) tea (used as a compress), and lemonjuice or cider vinegar (used as a face wash).

SynthesisDeciding which medication(s) should be prescribed foran adolescent who has acne is based on a synthesis ofseveral factors, including the types and numbers of le-sions present, the clinician’s impression of the severity ofdisease, the extent of acne, the patient’s experiences withmedications, and personal preferences. Information con-tained in Table 4 is designed to help develop treatmentplans. Beyond this, however, there is an art to treatingacne, and two clinicians may differ in their approach tothe same patient. Therapeutic choices also may be gov-erned by formulary restrictions. In some states, for exam-ple, prescription topical acne medications are not ap-proved for Medicaid reimbursement.

Follow-upA return visit typically is scheduled for 2 months aftertherapy has been initiated. However, patients should beencouraged to contact the office sooner with questions

or concerns regarding the use of their medications orpossible adverse effects. At the follow-up visit, the clini-cian can assess compliance, determine the patient’s im-pression of response to treatment, note the occurrence ofadverse effects, and assess the effect of therapy. Using thisinformation, the clinician can maintain or revise thetherapeutic plan.

SummaryAcne is the most common dermatologic disorder affect-ing adolescents. Although acne has no cure, clinicianscan offer therapy that may limit the emotional conse-quences of the disease and prevent or reduce the likeli-hood of physical scarring.

Suggested ReadingDickinson BD, Altman RD, Nielsen NH, Sterling ML. Drug inter-

actions between oral contraceptives and antibiotics. Obstet Gy-necol. 2001;98:853–860

Gelmetti CC, Krowchuk DP, Lucky AW. Acne. In: Schachner LA,Hansen RC, eds. Pediatric Dermatology. 3rd ed. London,United Kingdom: Harcourt Health Sciences; 2003:589–608

James WD. Acne. N Engl J Med. 2005;352:1463–1472Jick SS, Kremers HM, Vastlakis-Scaramozza C. Isotretinoin use and

risk of depression, psychotic symptoms, suicide, and attemptedsuicide. Arch Dermatol. 2000;136:1231–1236

Leyden JJ. New understandings of the pathogenesis of acne. J AmAcad Dermatol. 1995;32(suppl):S15–S25

Leyden J, Shalita A, Hordinsky M, Swinyer L, Stanczyk FZ, WeberME. Efficacy of a low-dose oral contraceptive containing20 mcg of ethinyl estradiol and 100 mcg of levonorgestrel forthe treatment of moderate acne: a randomized, placebo-controlled trial. J Am Acad Dermatol. 2002;47:399–409

Lucky AW, Henderson TA, Olson WH, et al. Effectiveness ofnorgestimate and ethinyl estradiol in treating moderate acnevulgaris. J Am Acad Dermatol. 1997;37:746–754

Thiboutot DM. Acne. An overview of clinical research findings.Dermatol Clin. 1997;15:97–109

Wysowski DK, Pitts M, Beitz J. An analysis of depression andsuicide in patients treated with isotretinoin. J Am Acad Derma-tol. 2001;45:515–519

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PIR QuizQuiz also available online at www.pedsinreview.org.

13. You are evaluating a 13-year-old boy who has numerous open and closed comedones involving theforehead, cheeks, and chin. There are no lesions on the chest or back. Of the following, the mostappropriate treatment is:

A. Benzoyl peroxide topically.B. Benzoyl peroxide/clindamycin topically.C. Erythromycin topically.D. Tetracycline orally.E. Tretinoin topically.

14. A 16-year-old girl who has mild facial comedonal and inflammatory acne treated effectively with benzoylperoxide 5% and tretinoin cream 0.025% presents with concern about an increase in acne lesions.Examination reveals approximately 20 inflammatory papules and pustules on her face and similar numbersof these lesions on her chest and back. There are rare comedones on the forehead. Of the following, themost appropriate next step in this patient’s management is to:

A. Increase the potency of the topical retinoid.B. Initiate an oral contraceptive.C. Initiate isotretinoin orally.D. Initiate tetracycline orally.E. Substitute benzoyl peroxide/clindamycin topically for benzoyl peroxide.

15. You are counseling a 15-year-old girl about routine skin care for her acne and factors that may worsenthe disease. Of the following, the statement that you are most likely to include in your discussion is that:

A. Eating fried foods will make acne worse.B. The application of oil-based moisturizers may induce acne lesions.C. The menstrual cycle does not affect disease severity.D. The use of an abrasive soap will be beneficial.E. Washing the skin frequently will prevent the appearance of acne lesions.

16. A true statement about acne is that:

A. Adolescent acne correlates best with chronologic age.B. Early in puberty, acne is characterized by inflammatory lesions.C. Genetic influences are unimportant in acne.D. P acnes primarily is responsible for causing follicular obstruction.E. The severity of acne correlates with sebum secretion.

17. An 8-year-old boy who has refractory seizures and severe developmental delay is brought to you fortreatment of acne. In his nasolabial folds and on his cheeks are erythematous papules. There are noblackheads or whiteheads. Of the following, the most likely diagnosis is:

A. Acne vulgaris.B. Adenoma sebaceum.C. Keratosis pilaris.D. Pityrosporum folliculitis.E. Steroid acne.

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DOI: 10.1542/pir.26-7-2502005;26;250Pediatrics in Review

Daniel P. KrowchukManaging Adolescent Acne : A Guide for Pediatricians

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