Improving More Than Superficial Appearances

Michael D. Pleacher, MD; William W. Dexter, MD

Sports Dermatology Series Editor:
William W. Dexter, MD

THE PHYSICIAN AND SPORTSMEDICINE - VOL 33 - NO. 9 - SEPTEMBER 2005

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In Brief: Acne vulgaris is a common skin condition that affects many athletes. Accurate diagnosis of the type and severity of acne lesions will help direct appropriate therapeutic interventions. Medications, including topical retinoids, topical antibiotics, oral antibiotics, and oral retinoids, are effective in treating acne. Side effects of acne therapy are common and generally mild, but athletes may require special counseling to minimize adverse effects of acne therapy. Treating acne may be challenging for both patient and physician, but with patience and perseverance, an appropriate treatment plan can provide dramatic improvements in the skin, emotional well-being, and social and athletic functioning.

Last autumn, during preparticipation physical examinations, a high school linebacker came to our clinic with severe cystic acne affecting his chest, back, and shoulders. The student was otherwise medically fit for play, but he was unable to tolerate wearing shoulder pads because of pressure on the deep cysts. He missed the entire football season while being treated with isotretinoin. This case illustrates the enormous impact acne can have on an athlete.

Acne vulgaris is a skin condition that commonly affects adolescents and young adults, including athletes. Acne rarely precludes athletic participation, except in cases as described above. Athletes using anabolic steroids may develop recalcitrant cystic acne on their backs and shoulders.¹ Occasionally, acne is indicative of systemic illness, such as polycystic ovary syndrome. Most commonly, however, acne is a skin problem resulting in poor cosmetic appearance. Although poor cosmesis may seem of minor importance to the physician, this may be quite devastating to patients.

Identifying the correct subtype and severity of acne will allow the practitioner to tailor a treatment strategy to each patient's specific needs. Physicians have a wide variety of options available for the treatment of acne, and some are more effective for particular acne subtypes than others. Side effects of acne therapy are generally low, although oral antibiotics and isotretinoin carry potentially significant side effects. Appropriate therapy will allow the athlete with acne to continue participating in sports, minimize medication side effects, and improve self confidence as well as the appearance of the skin.

Multifactorial Pathogenesis

Acne vulgaris is a disorder of the pilosebaceous unit, composed of a sebaceous gland and a hair follicle. The development of acne is a multifactorial process triggered by an increase in adrenal androgen production during puberty. In response, sebaceous glands increase in size and activity, producing more sebum.² Abnormal keratinization within the follicle leads to follicular canal obstruction and retention of keratin and sebum. A microcomedo subsequently develops³ and can then be colonized with the anaerobic diphtheroid Propionibacterium acnes.⁴ The body's immune response and the proliferation of P acnes leads to the development of pustules. Rupture of the wall of the pilosebaceous unit and resultant perifollicular inflammation produces deep cysts and nodules.^2,3

Epidemiology and Prevalence

Nearly every adult in Western society has had acneiform lesions at some point during their lives. Studies of younger adolescents^5,6 reveal that the overall prevalence of acne is 78%, with the prevalence rising to 91% to 93% in males and 79% in females 16 to 18 years old. A survey of adults over age 25 found that the overall prevalence of acne declines after adolescence, but up to 3% of adult men and 12% of adult women experience clinically significant acne.⁷ To our knowledge, no studies specifically examining the prevalence of acne in athletes have been reported.

Diagnosis and Classification of Acne

Evaluation of the patient who has acne should begin with a thorough history, including the timing and severity of acne outbreaks. Family history of acne should also be ascertained, because acne is a heritable condition. Detailed information on the patient's medical history and current medications may reveal underlying factors. With athletes, especially, it is essential to inquire about anabolic steroid use.¹ A review of systems should rule out any contributing endocrine abnormality. A thorough review of previous acne treatment should be documented, including responses and side effects experienced.

Often, the emotional and psychological effects of acne are overlooked by primary care physicians, but they are felt quite acutely by the patient. A survey of adolescents⁸ revealed that only 20% of those with acne were "not bothered at all" by their acne. Adolescents with more severe acne were less likely to enjoy participating in social activities. Gauging the impact that acne is having on the patient's emotional well-being and exhibiting empathy for the patient's condition may help create a positive doctor-patient relationship. Fostering such a relationship may encourage the patient to be more compliant with treatment and thereby improve overall outcomes.

The physical examination will usually confirm the diagnosis suggested by the history and allow accurate classification of both the type and severity of the acne lesions. The physician should examine the entirety of the skin, because acne may affect the face, neck, back, shoulders, and thighs. In addition to identifying the dominant type of lesion present and the areas affected, the practitioner should grade the severity of acne. Most general practitioners use a scale of mild (3 to 10 lesions), moderate (10 to 30 lesions), and severe (>30 lesions) to grade acne.

Acne can be broadly subdivided into inflammatory and noninflammatory lesions. Open and closed comedones are noninflammatory lesions. The closed comedo or whitehead is a firm, white papule visible to the naked eye. An open comedo, commonly called a blackhead, is created by dilation of the pore over a previously closed comedo (figure 1).³

Papules, pustules, cysts, and nodules are inflammatory lesions of acne that develop in a closed comedo when colonized by P acnes. The papule or pustule is characterized by a white, conical elevation surrounded by an inflammatory erythema. When the wall of the comedo ruptures and extends into the dermis, an intense inflammatory response results in a deep, erythematous, tender cyst or nodule (figures 2 and 3).³

Differential Diagnosis

Although the diagnosis of acne vulgaris is fairly straightforward, other acneiform disorders must be included in the differential diagnosis. Hot tub folliculitis, Malassezia folliculitis, and rosacea are common disorders that may be confused with acne vulgaris.

Hot tub folliculitis is a self-limited condition caused by colonization of follicles with Pseudomonas aeruginosa. The condition generally develops after the patient sits in a communal hot tub, and it resolves spontaneously within 1 to 2 weeks.

Another type of folliculitis is caused when the yeast Malassezia ovale colonizes the follicles (figure 4). It is characterized by pruritic follicular papules and pustules on the trunk, back, and upper arms. Absence of comedones and response to antifungal creams helps differentiate this condition from acne vulgaris.

Although rosacea is a distinct condition, it is a chronic disorder affecting the face that commonly coexists with acne vulgaris. Early stages of rosacea are characterized by persistent erythema and development of telangiectasia. Later stages of rosacea involve the development of papules and pustules that may be mistaken for the lesions of acne vulgaris.⁹

Initiating Treatment

Effective acne therapy begins with patient education. Myths surrounding etiologic factors are widely believed by adolescents. A survey⁸ of teenagers revealed that many believed that consuming greasy food (64%) or chocolate (50%) was responsible for the development of acne.

Dispelling these widely held misconceptions and instructing the patient on an appropriate gentle cleansing regimen are cornerstones of acne therapy. For most patients, washing twice a day is sufficient. Patients must also be counseled to avoid comedogenic substances found in many cosmetics, whenever possible. An exception to this advice is the use of sunblock for athletes competing in outdoor activities and for patients using oral antibiotics that cause photosensitivity. Some sunblock and sunscreen lotions contain comedogenic substances; in general, an oil-free water-based sunscreen is best.

After educating the patient, the physician may choose to start therapy with medications, including topical retinoids, topical antimicrobials, oral antimicrobials, and oral isotretinoin. These medications are effective in treating acne vulgaris by one or more of four key mechanisms of action: correcting altered follicular keratinization, decreasing sebum production, reducing bacterial colonization, or producing an anti-inflammatory effect.

Topical Retinoids

Topical retinoids, derivatives of vitamin A, treat acne by promoting normal epithelial desquamation. These medications act as keratolytics and reduce comedo formation. Topical retinoids are first-line agents for comedonal acne, and, because comedones are precursors of inflammatory lesions, they are effective adjuncts in the treatment of inflammatory acne. Commonly used topical retinoids are adapalene, tazarotene, and tretinoin (table 1).

TABLE 1. Topical Retinoids Used to Treat Acne Vulgaris Name Formulations Doses/   Day Possible Adverse Effects Pregnancy Class* Adapalene 0.1% cream 0.1% solution 0.1% gel 1 Erythema, irritation, peeling, photosensitivity C Tazarotene   0.05%, 0.1% cream 0.05%, 0.1% gel 1-2 Pruritus, erythema, desquamation, photosensitivity X Tretinoin 0.025%, 0.05%, 0.1% cream   0.01%, 0.025%, 0.1% gel 1 Erythema, peeling, pruritus, photosensitivity C * Pregnancy class C means safety for humans has not been determined. Either human reports and animal studies show some risks or not enough studies have been completed to determine the risks. Class C drugs should only be used if the benefits outweigh the possible risks to the fetus. Pregnancy class X means human reports and animal studies show documented fetal abnormalities. The possible risks are too great to use class X drugs during pregnancy.

Use of the topical retinoids for treatment of both comedonal and inflammatory lesions is supported in the literature. A randomized controlled trial¹⁰ comparing the effectiveness of tazarotene 0.1% and 0.05% gels with a placebo gel noted a 52% reduction in total lesions with tazarotene versus a 33% reduction with placebo for mild to moderate facial acne.

The topical retinoids vary slightly in efficacy when compared with one another. A meta-analysis of five randomized trials involving 900 patients with mild to moderate acne vulgaris revealed that with monotherapy, total lesion counts dropped by 53% with tretinoin 0.025% gel and by 57% with adapalene 0.1% gel.¹¹ Adapalene demonstrated more rapid efficacy and considerably greater local tolerability than tretinoin.

A randomized controlled trial¹² comparing tazarotene 0.1% gel and tretinoin 0.025% gel found a 54% reduction in the number of inflammatory lesions with tazarotene compared with 44% with tretinoin. Another randomized controlled trial¹³ revealed that tazarotene 0.1% gel reduced inflammatory lesions by 70% and noninflammatory lesions by 71%, compared with reductions of 55% and 48% observed with adapalene 0.1% gel. Both treatments were well tolerated, and tazarotene was more cost effective.

Common side effects of topical retinoid therapy include photosensitivity, erythema, dryness, and desquamation. Adapalene 0.1% gel was compared with isotretinoin 0.05% gel and 0.05% tretinoin cream for treatment of inflammatory acne in two recent studies.^14,15 All three preparations significantly reduced inflammatory lesions, but adapalene was associated with significantly fewer side effects. Tazarotene is associated with more local inflammation when compared with adapalene and tretinoin.^12,13

In summary, the topical retinoids have been shown to be effective monotherapeutic agents for comedonal and mild inflammatory acne. The greatest reductions in total lesion counts were observed with tazarotene 0.1% gel. Adapalene 0.1% gel induces fewer adverse effects, which may improve patient compliance and overall outcomes. Because topical retinoids induce photosensitivity, active patients must avoid excessive sun exposure and liberally use sunblock when participating in outdoor venues.

Topical Antimicrobials

Antibiotic therapy aimed at suppression of P acnes is a mainstay of therapy for pustular inflammatory acne lesions. Using topical antimicrobial agents such as benzoyl peroxide, clindamycin phosphate, and erythromycin (table 2) is supported in the literature by numerous studies. Products that combine benzoyl peroxide with an antibiotic or retinoid have also been studied extensively.

TABLE 2. Topical Antibiotics Used to Treat Acne Vulgaris Name Formulations Doses/   Day Possible Adverse Effects Pregnancy Class* Benzoyl peroxide 10% cream 5%, 10% lotion 5%, 10% gel 10% soap 1-2 Erythema, irritation, desquamation C Clindamycin phosphate 1% gel 1% lotion 1% solution 2 Dry skin, pruritus B Erythromycin 0.025%, 0.05%, 0.1% cream   0.01%, 0.025%, 0.1% gel 2 Dry skin B * Pregnancy class B means studies in animals have shown no risks, but not enough human studies have been completed to determine risks. Pregnancy class C means safety for humans has not been determined. Either human reports and animal studies show some risks or not enough studies have been completed to determine the risks. Class C drugs should only be used if the benefits outweigh the possible risks to the fetus.

Erythromycin 2% ointment was compared with placebo for treatment of mild to moderate acne in an early randomized controlled trial.¹⁶ Inflammatory lesions were reduced by 46% in the treatment group versus 19% in the placebo group.

Another randomized controlled trial¹⁷ comparing benzoyl peroxide 5% gel with erythromycin 1.5% lotion demonstrated equal efficacy between the two products in reducing overall acne severity and number of inflammatory lesions. Benzoyl peroxide also significantly reduced the number of noninflamed lesions, but erythromycin did not.

Products that combine benzoyl peroxide with a topical antibiotic are popular choices for treating patients who have inflammatory acne. A combination gel of 3% erythromycin and 5% benzoyl peroxide more effectively reduced inflammatory lesions when compared with a placebo, although improvement was not statistically different when compared with either product alone.¹⁸ The most dramatic effect was on combined inflammatory lesions (ie, papules and pustules).

Another large, well-designed randomized controlled study¹⁹ compared benzoyl peroxide 5% gel, clindamycin 1% gel, clindamycin 1% and benzoyl peroxide 5% combination gel, and a placebo gel. The combination product reduced inflammatory lesions by 61%, compared with 39% for benzoyl peroxide alone, 35% for clindamycin alone, and 5% for the placebo. A similar comparison study²⁰ demonstrated a 53% reduction in inflammatory lesions for clindamycin 1% and benzoyl peroxide 5% combination gel, a statistically significant greater reduction than either component alone or placebo.

Topical antimicrobial therapy remains a mainstay of treatment for mild to moderate pustular acne. The literature supports the use of combination topical antibiotic products containing benzoyl peroxide and clindamycin for the greatest reduction of inflammatory acne lesions.

Oral Antimicrobials

For moderate and severe cases of pustular acne, oral antibiotics with activity against P acnes can be used. The mechanism of action for oral antibiotics is multifaceted. Oral antibiotics reduce the P acnes population within the follicle and decrease the concentration of free fatty acids, which act as local irritants, in the sebum. Also, tetracycline has an inherent anti-inflammatory activity that reduces redness.

Typical treatment regimens use oral antibiotics in conjunction with a topical retinoid, topical benzoyl peroxide, or a topical antibiotic. Commonly used oral agents include erythromycin, minocycline hydrochloride, and tetracycline hydrochloride (table 3). Investigators are currently studying the efficacy of the newer macrolide antibiotics roxithromycin and azithromycin dihydrate in the treatment of acne.

TABLE 3. Oral Antibiotics and Isotretinoin Used to Treat Acne Vulgaris Name Formulations Doses/Day Possible Adverse Effects Pregnancy Class* Tetracycline hydrochloride 250 mg tablets 500 mg tablets 2 1 Photosensitivity, nausea, vomiting, esophagitis, dental staining D Erythromycin 250 mg, 333 mg tablets   500 mg tablets 3 2 Abdominal pain, nausea, vomiting, diarrhea B Minocycline hydrochloride 50 mg, 75 mg, 100 mg capsules 1 Dizziness, vertigo, photosensitivity D Isotretinoin 10 mg, 20 mg, 40 mg capsules 0.5-2 mg/kg/day   for 15-20 wk Dry eyes, dry mouth,joint pain, muscle aches, hyperlipidemia X *Pregnancy class B means studies in animals have shown no risks, but not enough human studies have been completed to determine risks. Pregnancy class D means that studies show there may be some risk to a developing human fetus, but the drug may still be used if the benefits outweigh the possible risks. Pregnancy class X means human reports and animal studies show documented fetal abnormalities. The possible risks are too great to use class X drugs during pregnancy.

Early studies comparing oral tetracycline at low doses (250 mg twice daily) with topical erythromycin 1.5% solution²¹ and topical clindamycin phosphate 1% solution²² revealed greater total lesion reductions with topical rather than oral antibiotics. Two studies^23,24 comparing higher doses of oral tetracycline (500 mg twice daily) with topical 1% clindamycin phosphate solution twice daily showed equivalent efficacy in reducing inflammatory lesions.

Oral tetracycline appears equivalent to oral erythromycin in reducing inflammatory lesions over a 12- week period, with reductions of papules and pustules ranging between 60% and 73%.²⁵ Tetracycline was associated with fewer side effects when compared with erythromycin. Another study²⁶ demonstrated that 94% of patients had improvement in acne severity when treated with both oral and topical tetracycline simultaneously, compared with improvement in only 57% of those treated with oral tetracycline and a topical placebo.

Oral minocycline has been used extensively for pustular acne, despite its relatively greater cost when compared with tetracycline or topical antimicrobials. A Cochrane database systematic review of data from 27 randomized controlled trials examined the efficacy of minocycline in treating acne.²⁷ The review concluded that minocycline was an effective treatment for moderate acne, but found no convincing evidence that it should be employed as a first-line agent in view of its expense.

A randomized controlled trial²⁸ compared five different topical and oral antimicrobial regimens for efficacy in treating mild to moderate inflammatory acne. Differences found between groups in terms of improving acne severity were small and statistically insignificant. Additionally, the cost-effectiveness of each regimen was evaluated. The least expensive regimen (benzoyl peroxide alone) was 12 times more cost-effective than the most expensive regimen (minocycline alone).

Common side effects of oral antibiotic therapy include gastrointestinal disturbances, photosensitivity, and vaginal candidiasis. Widespread and long-term use of oral antibiotics may lead to the development of resistant organisms. Using oral antibiotics may interfere with efficacy of oral contraceptives. Patients must be counseled about these common adverse effects particularly sensitivity to sun exposure. Using an effective sunblock when participating in outdoor activities is recommended.

Oral antimicrobial agents are effective in the treatment of inflammatory acne. When used to treat moderate and severe pustular acne, they are often combined with either a topical antimicrobial or a retinoid for greater effectiveness. Adverse drug reactions are common, and patients must be counseled about these known side effects.

Oral Retinoids

Severe nodular or cystic acne can be successfully treated with oral isotretinoin (13-cis-retinoic acid) (see table 3). A metabolite of vitamin A, isotretinoin inhibits the maturation of sebaceous glands, reduces the production of sebum, and alters the lipid composition of the skin surface. An early randomized controlled trial with isotretinoin²⁹ demonstrated complete acne clearing in 93% of patients. A long-term follow-up study³⁰ demonstrated that daily doses greater than 0.5 mg/kg and cumulative doses greater than 120 mg/kg reduce the rate of relapse. A micronized and more bioavailable formulation of isotretinoin at a dose of 0.4 mg/kg once daily (taken without food) was equivalent in efficacy to standard isotretinoin at doses of 1.0 mg/kg daily (divided in two doses and taken with food).³¹

A meta-analysis determined that the success rate of isotretinoin in treating moderate to severe acne was between 84% and 87%, with a relapse rate of 21%.³² A protocol for a Cochrane systematic review examining the efficacy and safety of oral isotretinoin for acne has been proposed, but results have not yet been published.³³

Adverse effects of treatment with isotretinoin are common but are generally well-tolerated. Almost all patients treated with standard isotretinoin will experience dry mouth, cheilitis, dry skin, and dry eyes. Before beginning treatment, athletes considering isotretinoin therapy should be advised of the potential for the common side effects of muscle and joint pain. More severe effects, including bone density changes, hyperlipidemia, and depression, are also seen in patients treated with isotretinoin, but these are very rare.

Isotretinoin is a powerful teratogen and is classified as a category X drug for use in pregnancy. The US Food and Drug Administration (FDA) requires a female patient to have two consecutive negative pregnancy tests before initiating isotretinoin therapy. Additionally, patients must document monthly negative pregnancy tests while using isotretinoin to remain on the medication, and women are counseled to use two different forms of effective birth control while being treated with isotretinoin. Despite these precautions, a significant number of isotretinoin-exposed pregnancies still occur. A report³⁴ documented 14 isotretinoin-exposed pregnancies in 1999 in California alone. Doctors who prescribe isotretinoin for women should be aware of this risk and should undertake the precautions outlined by the FDA when prescribing isotretinoin.

To prevent exposure to isotretinoin during pregnancy, a strengthened distribution program called iPLEDGE is being implemented by the drug's manufacturers. Doctors, patients, and pharmacies can get more information and register with iPLEDGE beginning August 22, 2005, at http://www.ipledgeprogram.com or by calling 1-866-495-0654. Starting December 31, 2005, all patients and prescribers must register and comply with requirements for office visits, counseling, birth control, and other restrictions.³⁵

Other Therapies

Additional treatments for acne (eg, hormonal therapy, light and laser therapy, herbal preparations) may be effective.

Among female patients, oral contraceptives often improve acne. A recent Cochrane systematic review³⁶ revealed that combination oral contraceptive pills reduce both inflammatory and noninflammatory acne lesions in women. No significant differences in efficacy were noted among different oral contraceptive types.

Phototherapy, with either natural sunlight or lamp-generated ultraviolet A and ultraviolet B radiation, is generally accepted as a modestly effective therapy, but the inconvenience of repeated visits and the risk of carcinogenicity limit its clinical utility.³⁷ Studies involving pulsed-dye lasers have produced conflicting results, and therefore require greater study before widespread use can be endorsed.^38,39

Acne Mechanica

Initiated by mechanical stresses on the skin, acne mechanica is a superficial folliculitis with acneiform lesions and an inflammatory appearance. The affected body areas are those subjected to repetitive mechanical forces of pressure, friction, rubbing, squeezing, or stretching.⁴⁰ Among athletes, areas covered by shoulder pads, chin straps, and helmets are commonly affected, as are the back, shoulders, and axilla of weight lifters. This condition can arise in patients who have no history of acne vulgaris.⁴¹

In one study,⁴² at least 15% of high school football players had nuchal acne mechanica, but prevalence among collegiate football players was only 1.2%. Rarely, acne mechanica can be associated with a more chronic condition termed acne keloidalis nuchae. In many cases, however, acne keloidalis nuchae occurs without acne mechanica. Acne keloidalis nuchae is characterized by firm, keloid-like nodules that may exceed several millimeters in diameter. This condition occurs exclusively in African-American athletes but is not associated with any personal or family history of keloid formation.⁴²

Resolution of acne mechanica routinely follows removal of the inciting mechanical stress. For most athletes, this condition resolves after completing their season. Acne mechanica may be prevented with thorough regular cleansing of the involved skin. A clean cotton t-shirt worn under athletic pads may also help prevent the development of acne mechanica. Treatments for acne vulgaris are not routinely helpful in treating acne mechanica.

Coordinated Efforts for Care

The process of diagnosing and treating acne in athletes is not substantially different from other populations of patients. However, since most athletes spend a portion of time training outdoors, care must be taken to prevent sun-induced damage to photosensitive skin in athletes treated with topical retinoids and oral antibiotics. Certain patient history items, such as the possibility of steroid use or mechanical forces as contributing factors, deserve special attention in the athlete.

Accurate recognition of various acne lesions and grades of severity will allow the physician to appropriately prescribe treatment. A successful treatment plan hinges on educating the patient and coordinating efforts between the patient and physician to find a medication regimen that maximizes reduction of lesions and minimizes adverse effects.

References

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Dr Pleacher is a sports medicine physician with Intermountain Health Care in Layton, Utah, and Dr Dexter is the director of the Sports Medicine Program at Maine Medical Center in Portland, Maine. Address correspondence to Michael D. Pleacher, MD, 245 West 1350 North, Centerville, UT 84014; e-mail to pleacherm@hotmail.com.

Disclosure information: Drs Pleacher and Dexter disclose no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use.