Acne treatment: Easy ways to improve your care

CASE Janis S, an otherwise healthy 19-year-old, is in your office, seeking treatment for acne. She reports she has tried various over-the-counter (OTC) creams in recent months, but has seen little improvement. The acne first appeared about 5 years ago, and her pediatrician prescribed topical adapalene and doxycycline. The treatment helped, but she says her face never fully cleared up; over the past year, the acne has gotten worse.

On examination, you find several nodules and comedones on the patient’s face, chest, and back. Ms. S confides in you that the acne—particularly on her face—kept her from going to the senior prom.

More than 80% of adolescents and adults develop acne vulgaris at some point in their lives, and in at least 15% to 20% of cases, the acne is moderate to severe.¹ Although acne typically starts in early puberty, it can continue well into adulthood.² Females typically develop acne at an earlier age than males. There are no other sex or racial differences.³

Regardless of the age at which acne develops, it has substantial psychological effects, including embarrassment, shame, depression, anxiety, social isolation—and in extreme cases, suicidal ideation.⁴ This evidence-based update will better prepare you to provide optimal medical therapy—and alleviate patients’ emotional distress—without delay.

The pathophysiology of acne vulgaris

The American Academy of Dermatology (AAD) defines acne as a “chronic inflammatory dermatosis which is notable for open and/or closed comedones (blackheads and whiteheads) and inflammatory lesions, including papules, pustules, and nodules….”⁵ The underlying etiology is best described as a cascade of events involving the pilosebaceous unit.

Normally, single keratinocytes are shed into the follicular lumen for excretion. In acne, this process is disrupted and the keratinocytes accumulate, becoming interwoven with monofilaments and lipid droplets. The lipids, cellular debris, and excessive sebum, as well as the overgrowth of Propionibacterium acnes, block the follicles;⁶ the bacterial overgrowth can generate inflammation, as well.⁷ Areas rich in sebaceous glands, such as the face, neck, chest, upper arms, and back, are the sites at which acne is most likely to develop.

Clockwise, from top: closed comedones; open comedones; pustules; and scarring.

Androgen receptors play a role
For many years, the underlying pathophysiology of acne vulgaris was thought to be lesion progression, with microcomedone formation leading to both closed and open comedones. Emerging evidence has led to a deeper understanding of acne development. Sebum is now known to have androgen receptors (nuclear transcription factor Fox O1), which are modulated by insulinlike-growth factor 1 (IGF-1) and insulin.^8,9 Research to determine whether these receptors can be influenced by diet and melanocortins is ongoing.^8,10

Evidence has also shown that inflammation around the follicles and follicular differentiation precede bacterial overgrowth,⁷ and that P acnes overgrowth exacerbates the blockage and inflammation by creating a biofilm that plugs the follicles. Inflammation is one of the main complications of acne, causing hyperpigmentation and scarring.

These factors increase the risk
There are numerous risk factors for acne, ranging from genetics to stress to certain medications (TABLE 1).¹¹ Although the exact genetic penetrance is unknown, acne often affects multiple family members;^1,12 genetics is also associated with an increase in androgens, such as that found in patients with Cushing syndrome, polycystic ovary syndrome (PCOS), and congenital adrenal hyperplasia.¹³

Emotional and physical stress can increase the risk for acne,¹⁴ with the latter often related to excessive friction on the skin caused by sweat bands or helmet strips. Cosmetics that plug the follicles are a risk factor for acne, as well.

TABLE 1
Drugs that are potential acne triggers

The patient has acne, but how severe? 

Because acne is often diagnosed clinically, there is often no need for routine testing. Nor is a bacterial culture for P acnes necessary.

If the patient has signs and symptoms suggestive of an endocrine disorder, however—eg, infertility, PCOS, or hirsutism—consider checking free testosterone, dehydroepiandrosterone sulfate (DHEA), luteinizing/follicle-stimulating hormones (LH/FSH), 17-alpha-progesterone, adrenocorticotropic hormone (ACTH), and/or dexamethasone suppression. Other indicators of a need for endocrine testing include male or female pattern balding, an abnormal menstrual cycle, acanthosis nigricans, and truncal obesity.^5,6

Numerous acne classification systems have been developed; some are based on the type of lesions (ie, comedonal, papulopustular, nodulocystic), while others also consider the number of each type of lesion and areas affected.¹⁵ In 2002, the US Food and Drug Administration (FDA) defined the components of a Global Acne Severity Scale as having 6 grades (0-5), with 0 for normal skin and 5 representing a predominance of highly inflammatory lesions with a variable number of papules/pustules and nodulocystic lesions.¹⁶

The AAD’S classification system has only 3 grades—mild, moderate, and severe—and is one of the easiest to use:

• Mild cases have few to several papules and pustules, but no nodules
• Moderate cases have more papules and pustules, with a few nodules
• Severe cases have numerous papules, pustules, and nodules.⁵

CASE Ms. S is in obvious emotional distress, and her acne needs to be treated aggressively. Because of the emotional impact and the fact that she has lesions on several body parts, her case is classified as severe (and would be even if her face had only a few lesions).

Treatment: Prevention of new lesions is paramount

Preventing new formations is a key focus of acne therapy, and patients should be advised that it may take weeks for results to be seen. Nonetheless, aggressive treatment of inflammatory lesions is necessary to prevent scarring. Because most patients have both inflammatory and bacterial lesions, it is important to use combined therapies, including topical or oral antibiotics, to treat P acnes and inflammation (TABLE 2).^13,17-23

TABLE 2
Acne classification helps guide treatment decisions^13,17-23

Topicals are the cornerstone of treatment
Retinoids and benzoyl peroxide topicals are the foundation of therapy for both comedonal and inflammatory acne,¹⁷ regardless of severity. Both are recommended by the AAD. But evidence suggests that only 55% of dermatologists and 10% of primary care providers recommend them.^19,20

Retinoids inhibit microcomedone formation and regulate follicular keratinocytes, which have anti-inflammatory properties and help to prevent the formation of new lesions. Patients should be warned that topical retinoids can cause irritation, erythema, desquamation, pruritus, and burning. To reduce the adverse effects, advise patients to start retinoid therapy slowly, at a reduced frequency (eg, every other day or every third day) and shorter contact (washing it off after one to 4 hours for a week, then increasing the contact time). When it is clear that the medication is well tolerated, the frequency and amount can be increased. Use of the topical, as tolerated, should continue as long as the potential acne problem remains.

There are 3 retinoid formulations on the market—adapalene, tretinoin, and tazarotene—all of which have been shown to be effective. Adapalene is the least irritating and the most stable, and can be safely combined with benzoyl peroxide and topical antibiotics. If tretinoin and benzoyl peroxide are used concurrently, tretinoin should be applied at night and benzoyl peroxide during the day. To reduce the risk of inactivating the topical agents, advise patients not to use other skin products in conjunction with topical therapy.

Benzoyl peroxide, which is available as a cleanser, gel, or wash, affects keratinocyte dysmaturation, P acnes, and inflammation.¹¹ The antibacterial activity is due to its oxidation. Benzoyl peroxide is available both OTC and by prescription, with concentrations ranging from 2% to 10%. Salicylic acid (2%-3%), a well-tolerated keratolytic agent, is often used with benzoyl peroxide, as well. Azelaic acid, sodium sulfacetamide, and dapsone are other topicals that have been found to be effective in treating acne.

Topical antibiotics, most commonly clindamycin 1% or sodium sulfacetamide, also affect both P acnes and inflammation,²⁴ although the exact mechanism is unknown. Available in solution or as a gel or lotion, topical antibiotics can be combined with benzoyl peroxide. Use of topical erythromycin has declined in recent years because it has a higher rate of bacterial resistance.^9,21

When to add oral antibiotics
When topical treatment does not produce the desired result or cannot be tolerated, oral antibiotics may be introduced, either as an addition or replacement. Like topicals, oral antibiotics have both antimicrobial and anti-inflammatory properties.

Tetracycline antibiotics (ie, doxycycline and minocycline) are first-line oral therapy.²¹ Minocycline has been found to be the most potent agent in this drug class; tetracycline is the least.²² Tetracyclines can cause tooth discoloration and inhibit skeletal growth, and are contraindicated for children younger than 10 years and pregnant women.

Photosensitivity is an adverse effect of tetracycline antibiotics, so patients should be advised to cover up and avoid sun exposure. Other adverse effects, particularly of minocycline, include dizziness, lupus-like syndrome, pseudotumor cerebri, skin and mucosal pigmentation, serum sickness, and hepatitis. If the patient is taking an oral contraceptive pill (OCP) concurrently for family planning, she should be advised that oral antibiotics have the potential to reduce the efficacy of the OCP.

Other oral antibiotics sometimes used to treat acne include erythromycin, trimethoprim-sulfamethoxazole, amoxicillin, and azithromycin, but data on their efficacy are limited. Erythromycin has similar potency to tetracycline, but may need to be taken 2 to 4 times a day and may cause more gastrointestinal disturbances. Cephalosporins, fluoroquinolones, aminoglycosides, chloramphenicol, sulfonamides/sulfur, and gyrase inhibitors should not be used for acne because of a lack of efficacy.⁶

Diagnostic challenge: Is it acne?

No, it isn’t. Pustules on the face, like those on the patient pictured here, are a common manifestation of acne. But facial lesions alone are not sufficient for a definitive diagnosis. In fact, the pustules that this 59-year-old woman sought treatment for were correctly diagnosed as perioral dermatitis. The tip-off? The lack of comedones and the distribution of the lesions, which were concentrated around the mouth.

Regardless of the type of oral antibiotic prescribed, it should be tried for about 3 months (8-16 weeks) and discontinued once improvement occurs. If no improvement is seen within 3 months, consider changing antibiotics due to resistance or adding antifungal therapy for Pityrosporum and Malassezia species.⁶

Initiating isotretinoin therapy: An evidence-based approach

Oral isotretinoin is the only potential cure for acne vulgaris. The cure rate is about 30% to 40% (with about 20% of patients developing a recurrence that requires retreatment within one to 3 years).²⁵

Isotretinoin is FDA approved for severe nodulocystic acne, but several organizations, including the AAD and the Global Alliance to Improve Outcomes in Acne, recommend its use for milder cases.^25,26 It is also an excellent treatment for other forms of severe acne, such as acne fulminans and acne conglobata. Accutane is no longer available, but 5 other formulations of isotretinoin are on the market.

Because isotretinoin is a category X teratogen, all providers and patients must register with iPLEDGE (www.ipledgeprogram.com), an FDA-approved mandatory risk management program. Before starting to take isotretinoin, females of childbearing age are required to undergo 2 pregnancy tests; they must also agree to use 2 forms of program-approved birth control and submit to monthly pregnancy tests.

Patients on isotretinoin also need to be monitored for depression.²⁷ Other potential adverse effects include hepatitis, hypertriglyceridemia, arthralgia, myalgias, and inflammatory bowel disease.^28,29 Dry skin and mucosa are the most common adverse effects, and patients should be advised to use moisturizers regularly.

A better dosing regimen?
The standard starting dose of isotretinoin is 0.25 to 1 mg/kg/d, divided and taken twice a day, then titrated upward monthly to a maximum daily dose of 2 mg/kg. The goal is for the total intake of isotretinoin to be 120 to 150 mg/kg. So, for example, the goal for a patient weighing 60 kg might be a cumulative intake of 7200 mg (120 mg/kg × 60 kg), taken in doses of 20 mg BID (40 mg/d) for 180 days.

The medication should be taken with food (especially with fatty food) for better absorption. Treatment duration has typically been 16 to 32 weeks, with an average of 20 weeks, with the daily dose lowered in patients requiring treatment for a longer period of time. Continuous use of isotretinoin is more effective than taking it intermittently.²⁶

Lower dosages? While that standard regimen has been adequate in the management of acne vulgaris, emerging evidence suggests that dosages of isotretinoin as low as 5 mg/d are equally effective and have significantly fewer adverse effects.³⁰ Relapse continues to be a problem. Risk factors for relapse include a macrocomedonal pattern of acne, smoking, and age, with patients <14 years and >25 years at higher risk.³⁰ While lower dosing was previously thought to be associated with greater risk of relapse, this appears to be related less to the cumulative dose of 120 to 150 mg/kg and more to the duration of sebaceous gland suppression.³⁰

Based on the latest evidence, important changes in isotretinoin administration are called for—specifically, using a much lower dose (0.25-0.5 mg/kg, divided into 2 daily doses) for a longer period of time.³⁰ While the traditional dosing generally requires a 3- to 5-month course of treatment, the lower dosing can take 6 to 8 months.

Who's a candidate for hormonal therapy?

Any hormone that has antiandrogenic properties can have a beneficial effect on acne.

The most common hormonal therapy is an estrogen-progestin combination OCP.^23,31 Progesterone-only OCPs should not be used as they can worsen acne.

In theory, any OCP that contains estrogen can work because of its androgenic properties. The estrogen appears to suppress sebaceous gland activity. OCPs with FDA approval for the treatment of acne include Estrostep Fe (norethindrone/ethinyl estradiol [EE]), Ortho Tricyclen (norgestimate/EE), and Yasmin and Beyaz (drospirenone/EE). With any OCP, the effect is gradual, and it can take 3 to 4 months for patients to see an improvement. OCPs are an excellent choice for women with moderate-to-severe acne or those suffering from hirsutism and seborrhea.

Other hormonal therapies—which are not FDA approved for acne treatment—include spironolactone, cyproterone, and flutamide.²⁴ There is no evidence to support the use of finasteride or cyproterone.

Spironolactone is the most studied and has modest benefits at 100 to 150 mg/d.²² Caution is needed when using spironolactone, as gynecomastia, hyperkalemia, and agranulocytosis are potential adverse effects. It is important to closely monitor the blood pressure, chemistry, and cell count of patients taking spironolactone.

CASE Because Ms. S is sexually active and does not wish to become pregnant, she is a candidate for an OCP. You prescribe a pill containing norgestimate and EE, add a topical retinoid to her regimen, and schedule a return visit in 3 months to evaluate the effectiveness of therapy. If there is little improvement, you will recommend isotretinoin at that time.

Talk to patients about lifestyle modifications

Although the role of lifestyle changes in acne treatment is controversial, there is some evidence to suggest that these modifications are worth considering:

Glycemic load. In Western society, where the typical diet includes foods with a high glycemic index, there appears to be a higher prevalence of acne compared with regions where foods with a low glycemic index (≤55-60) are the mainstay. A low glycemic load appears to reduce both the occurrence and severity of acne.¹⁷ Thus, patients who are willing to make dietary changes should be advised to consume foods with a lower glycemic index, such as peanuts and green vegetables.

Dairy. Milk is believed to have an androgenic effect, and dairy products in general have a positive correlation with acne. Thus, a reduction in milk intake has been found to improve acne.^18,32 Stress the importance of calcium supplementation for patients whose dairy consumption is reduced or eliminated.

Fish oil. Omega-6 fatty acid, found in fish oil, has anti-inflammatory properties, and an increase in foods rich in omega-3 fatty acid (eg, salmon, sardines, walnuts) has been associated with improvement of acne.¹⁷

Probiotics. There is limited evidence for probiotics as a therapy for acne. They do appear to regulate inflammatory cytokines within the skin and to upregulate the IGF-1, both of which influence the formation of acne.^10,33

Other treatment options to consider

Injections, chemical peels, and/or laser treatments may be considered as adjunctive therapy or when standard therapies fail.

Steroid injections. This treatment regimen centers around a midpotency steroid that is diluted with normal saline and is introduced into each lesion until the lesion is distended and/or blanched. There are limited data on the use of corticosteroid injections for acne, however, and these injections are reserved for severe cases to reduce inflammation. Potential adverse effects include hyperglycemia, obesity, and Cushing traits.

Chemical peels are used to decrease both inflammatory and noninflammatory lesions, and are typically well tolerated. In one study, more than 95% of patients were satisfied with the results.^11,34

Various chemicals have been used, including alpha-hydroxyl acid (glycolic acid), beta-hydroxyl acid (salicylic acid), and Jessner’s solution, with equal efficacy.^35-38 Chemical peels can be used on patients with darker skin, but caution is required to avoid dyschromia.³⁹ Other adverse effects include dry skin, crusting, and facial erythema. More adverse effects have been reported with glycolic acid vs salicylic acid.³⁷

Laser therapies include photodynamic therapy—blue light with amino-luvanic acid—and phototherapy (blue light alone).^40-42P acnes accumulate photosensitizing porphyrins in the comedones; when the laser therapy is applied, the porphyrins absorb the light source and destroy the bacteria.

Laser treatment can also be used for scarring. Ablative laser resurfacing significantly improves acne scars; nonablative and fractional CO₂ laser modalities can also be used, with minimal downtime and no serious complications.⁴³

Other complementary therapies, including aloe vera, pyridoxine, kampo, tea tree extract, and fruit-based acids, have little or no data regarding their efficacy.

The importance of maintenance therapy

With the exception of patients whose acne was cured or who achieved remission with isotretinoin, maintenance is required once the desired appearance is reached. Without it, recurrence is likely—possibly within as little as 4 weeks.

For most patients, a topical retinoid is the only medication that should be continued. Tell patients to apply it nightly and to call for an appointment if an acne flare-up occurs.

CASE When Ms. S comes in for a follow-up visit, her acne is cleared except for a couple of lesions on her back and she is happy with the results. You advise her to continue on the OCP to avoid a recurrence but caution her that in a small percentage of cases, the acne may worsen even in women who continue to take OCPs and topicals. You agree to initiate isotretinoin if this occurs.

CORRESPONDENCE
Tam T. Nguyen, MD, San Joaquin General Hospital, 500 West Hospital Road, Suite 1103, French Camp, CA 95231; ttnguyen@sjgh.org

CASE Janis S, an otherwise healthy 19-year-old, is in your office, seeking treatment for acne. She reports she has tried various over-the-counter (OTC) creams in recent months, but has seen little improvement. The acne first appeared about 5 years ago, and her pediatrician prescribed topical adapalene and doxycycline. The treatment helped, but she says her face never fully cleared up; over the past year, the acne has gotten worse.

On examination, you find several nodules and comedones on the patient’s face, chest, and back. Ms. S confides in you that the acne—particularly on her face—kept her from going to the senior prom.

More than 80% of adolescents and adults develop acne vulgaris at some point in their lives, and in at least 15% to 20% of cases, the acne is moderate to severe.¹ Although acne typically starts in early puberty, it can continue well into adulthood.² Females typically develop acne at an earlier age than males. There are no other sex or racial differences.³

Regardless of the age at which acne develops, it has substantial psychological effects, including embarrassment, shame, depression, anxiety, social isolation—and in extreme cases, suicidal ideation.⁴ This evidence-based update will better prepare you to provide optimal medical therapy—and alleviate patients’ emotional distress—without delay.

The pathophysiology of acne vulgaris

The American Academy of Dermatology (AAD) defines acne as a “chronic inflammatory dermatosis which is notable for open and/or closed comedones (blackheads and whiteheads) and inflammatory lesions, including papules, pustules, and nodules….”⁵ The underlying etiology is best described as a cascade of events involving the pilosebaceous unit.

Normally, single keratinocytes are shed into the follicular lumen for excretion. In acne, this process is disrupted and the keratinocytes accumulate, becoming interwoven with monofilaments and lipid droplets. The lipids, cellular debris, and excessive sebum, as well as the overgrowth of Propionibacterium acnes, block the follicles;⁶ the bacterial overgrowth can generate inflammation, as well.⁷ Areas rich in sebaceous glands, such as the face, neck, chest, upper arms, and back, are the sites at which acne is most likely to develop.

Clockwise, from top: closed comedones; open comedones; pustules; and scarring.

Androgen receptors play a role
For many years, the underlying pathophysiology of acne vulgaris was thought to be lesion progression, with microcomedone formation leading to both closed and open comedones. Emerging evidence has led to a deeper understanding of acne development. Sebum is now known to have androgen receptors (nuclear transcription factor Fox O1), which are modulated by insulinlike-growth factor 1 (IGF-1) and insulin.^8,9 Research to determine whether these receptors can be influenced by diet and melanocortins is ongoing.^8,10

Evidence has also shown that inflammation around the follicles and follicular differentiation precede bacterial overgrowth,⁷ and that P acnes overgrowth exacerbates the blockage and inflammation by creating a biofilm that plugs the follicles. Inflammation is one of the main complications of acne, causing hyperpigmentation and scarring.

These factors increase the risk
There are numerous risk factors for acne, ranging from genetics to stress to certain medications (TABLE 1).¹¹ Although the exact genetic penetrance is unknown, acne often affects multiple family members;^1,12 genetics is also associated with an increase in androgens, such as that found in patients with Cushing syndrome, polycystic ovary syndrome (PCOS), and congenital adrenal hyperplasia.¹³

Emotional and physical stress can increase the risk for acne,¹⁴ with the latter often related to excessive friction on the skin caused by sweat bands or helmet strips. Cosmetics that plug the follicles are a risk factor for acne, as well.

TABLE 1
Drugs that are potential acne triggers

The patient has acne, but how severe? 

Because acne is often diagnosed clinically, there is often no need for routine testing. Nor is a bacterial culture for P acnes necessary.

If the patient has signs and symptoms suggestive of an endocrine disorder, however—eg, infertility, PCOS, or hirsutism—consider checking free testosterone, dehydroepiandrosterone sulfate (DHEA), luteinizing/follicle-stimulating hormones (LH/FSH), 17-alpha-progesterone, adrenocorticotropic hormone (ACTH), and/or dexamethasone suppression. Other indicators of a need for endocrine testing include male or female pattern balding, an abnormal menstrual cycle, acanthosis nigricans, and truncal obesity.^5,6

Numerous acne classification systems have been developed; some are based on the type of lesions (ie, comedonal, papulopustular, nodulocystic), while others also consider the number of each type of lesion and areas affected.¹⁵ In 2002, the US Food and Drug Administration (FDA) defined the components of a Global Acne Severity Scale as having 6 grades (0-5), with 0 for normal skin and 5 representing a predominance of highly inflammatory lesions with a variable number of papules/pustules and nodulocystic lesions.¹⁶

The AAD’S classification system has only 3 grades—mild, moderate, and severe—and is one of the easiest to use:

• Mild cases have few to several papules and pustules, but no nodules
• Moderate cases have more papules and pustules, with a few nodules
• Severe cases have numerous papules, pustules, and nodules.⁵

CASE Ms. S is in obvious emotional distress, and her acne needs to be treated aggressively. Because of the emotional impact and the fact that she has lesions on several body parts, her case is classified as severe (and would be even if her face had only a few lesions).

Treatment: Prevention of new lesions is paramount

Preventing new formations is a key focus of acne therapy, and patients should be advised that it may take weeks for results to be seen. Nonetheless, aggressive treatment of inflammatory lesions is necessary to prevent scarring. Because most patients have both inflammatory and bacterial lesions, it is important to use combined therapies, including topical or oral antibiotics, to treat P acnes and inflammation (TABLE 2).^13,17-23

TABLE 2
Acne classification helps guide treatment decisions^13,17-23

Topicals are the cornerstone of treatment
Retinoids and benzoyl peroxide topicals are the foundation of therapy for both comedonal and inflammatory acne,¹⁷ regardless of severity. Both are recommended by the AAD. But evidence suggests that only 55% of dermatologists and 10% of primary care providers recommend them.^19,20

Retinoids inhibit microcomedone formation and regulate follicular keratinocytes, which have anti-inflammatory properties and help to prevent the formation of new lesions. Patients should be warned that topical retinoids can cause irritation, erythema, desquamation, pruritus, and burning. To reduce the adverse effects, advise patients to start retinoid therapy slowly, at a reduced frequency (eg, every other day or every third day) and shorter contact (washing it off after one to 4 hours for a week, then increasing the contact time). When it is clear that the medication is well tolerated, the frequency and amount can be increased. Use of the topical, as tolerated, should continue as long as the potential acne problem remains.

There are 3 retinoid formulations on the market—adapalene, tretinoin, and tazarotene—all of which have been shown to be effective. Adapalene is the least irritating and the most stable, and can be safely combined with benzoyl peroxide and topical antibiotics. If tretinoin and benzoyl peroxide are used concurrently, tretinoin should be applied at night and benzoyl peroxide during the day. To reduce the risk of inactivating the topical agents, advise patients not to use other skin products in conjunction with topical therapy.

Benzoyl peroxide, which is available as a cleanser, gel, or wash, affects keratinocyte dysmaturation, P acnes, and inflammation.¹¹ The antibacterial activity is due to its oxidation. Benzoyl peroxide is available both OTC and by prescription, with concentrations ranging from 2% to 10%. Salicylic acid (2%-3%), a well-tolerated keratolytic agent, is often used with benzoyl peroxide, as well. Azelaic acid, sodium sulfacetamide, and dapsone are other topicals that have been found to be effective in treating acne.

Topical antibiotics, most commonly clindamycin 1% or sodium sulfacetamide, also affect both P acnes and inflammation,²⁴ although the exact mechanism is unknown. Available in solution or as a gel or lotion, topical antibiotics can be combined with benzoyl peroxide. Use of topical erythromycin has declined in recent years because it has a higher rate of bacterial resistance.^9,21

When to add oral antibiotics
When topical treatment does not produce the desired result or cannot be tolerated, oral antibiotics may be introduced, either as an addition or replacement. Like topicals, oral antibiotics have both antimicrobial and anti-inflammatory properties.

Tetracycline antibiotics (ie, doxycycline and minocycline) are first-line oral therapy.²¹ Minocycline has been found to be the most potent agent in this drug class; tetracycline is the least.²² Tetracyclines can cause tooth discoloration and inhibit skeletal growth, and are contraindicated for children younger than 10 years and pregnant women.

Photosensitivity is an adverse effect of tetracycline antibiotics, so patients should be advised to cover up and avoid sun exposure. Other adverse effects, particularly of minocycline, include dizziness, lupus-like syndrome, pseudotumor cerebri, skin and mucosal pigmentation, serum sickness, and hepatitis. If the patient is taking an oral contraceptive pill (OCP) concurrently for family planning, she should be advised that oral antibiotics have the potential to reduce the efficacy of the OCP.

Other oral antibiotics sometimes used to treat acne include erythromycin, trimethoprim-sulfamethoxazole, amoxicillin, and azithromycin, but data on their efficacy are limited. Erythromycin has similar potency to tetracycline, but may need to be taken 2 to 4 times a day and may cause more gastrointestinal disturbances. Cephalosporins, fluoroquinolones, aminoglycosides, chloramphenicol, sulfonamides/sulfur, and gyrase inhibitors should not be used for acne because of a lack of efficacy.⁶

Diagnostic challenge: Is it acne?

No, it isn’t. Pustules on the face, like those on the patient pictured here, are a common manifestation of acne. But facial lesions alone are not sufficient for a definitive diagnosis. In fact, the pustules that this 59-year-old woman sought treatment for were correctly diagnosed as perioral dermatitis. The tip-off? The lack of comedones and the distribution of the lesions, which were concentrated around the mouth.

Regardless of the type of oral antibiotic prescribed, it should be tried for about 3 months (8-16 weeks) and discontinued once improvement occurs. If no improvement is seen within 3 months, consider changing antibiotics due to resistance or adding antifungal therapy for Pityrosporum and Malassezia species.⁶

Initiating isotretinoin therapy: An evidence-based approach

Oral isotretinoin is the only potential cure for acne vulgaris. The cure rate is about 30% to 40% (with about 20% of patients developing a recurrence that requires retreatment within one to 3 years).²⁵

Isotretinoin is FDA approved for severe nodulocystic acne, but several organizations, including the AAD and the Global Alliance to Improve Outcomes in Acne, recommend its use for milder cases.^25,26 It is also an excellent treatment for other forms of severe acne, such as acne fulminans and acne conglobata. Accutane is no longer available, but 5 other formulations of isotretinoin are on the market.

Because isotretinoin is a category X teratogen, all providers and patients must register with iPLEDGE (www.ipledgeprogram.com), an FDA-approved mandatory risk management program. Before starting to take isotretinoin, females of childbearing age are required to undergo 2 pregnancy tests; they must also agree to use 2 forms of program-approved birth control and submit to monthly pregnancy tests.

Patients on isotretinoin also need to be monitored for depression.²⁷ Other potential adverse effects include hepatitis, hypertriglyceridemia, arthralgia, myalgias, and inflammatory bowel disease.^28,29 Dry skin and mucosa are the most common adverse effects, and patients should be advised to use moisturizers regularly.

A better dosing regimen?
The standard starting dose of isotretinoin is 0.25 to 1 mg/kg/d, divided and taken twice a day, then titrated upward monthly to a maximum daily dose of 2 mg/kg. The goal is for the total intake of isotretinoin to be 120 to 150 mg/kg. So, for example, the goal for a patient weighing 60 kg might be a cumulative intake of 7200 mg (120 mg/kg × 60 kg), taken in doses of 20 mg BID (40 mg/d) for 180 days.

The medication should be taken with food (especially with fatty food) for better absorption. Treatment duration has typically been 16 to 32 weeks, with an average of 20 weeks, with the daily dose lowered in patients requiring treatment for a longer period of time. Continuous use of isotretinoin is more effective than taking it intermittently.²⁶

Lower dosages? While that standard regimen has been adequate in the management of acne vulgaris, emerging evidence suggests that dosages of isotretinoin as low as 5 mg/d are equally effective and have significantly fewer adverse effects.³⁰ Relapse continues to be a problem. Risk factors for relapse include a macrocomedonal pattern of acne, smoking, and age, with patients <14 years and >25 years at higher risk.³⁰ While lower dosing was previously thought to be associated with greater risk of relapse, this appears to be related less to the cumulative dose of 120 to 150 mg/kg and more to the duration of sebaceous gland suppression.³⁰

Based on the latest evidence, important changes in isotretinoin administration are called for—specifically, using a much lower dose (0.25-0.5 mg/kg, divided into 2 daily doses) for a longer period of time.³⁰ While the traditional dosing generally requires a 3- to 5-month course of treatment, the lower dosing can take 6 to 8 months.

Who's a candidate for hormonal therapy?

Any hormone that has antiandrogenic properties can have a beneficial effect on acne.

The most common hormonal therapy is an estrogen-progestin combination OCP.^23,31 Progesterone-only OCPs should not be used as they can worsen acne.

In theory, any OCP that contains estrogen can work because of its androgenic properties. The estrogen appears to suppress sebaceous gland activity. OCPs with FDA approval for the treatment of acne include Estrostep Fe (norethindrone/ethinyl estradiol [EE]), Ortho Tricyclen (norgestimate/EE), and Yasmin and Beyaz (drospirenone/EE). With any OCP, the effect is gradual, and it can take 3 to 4 months for patients to see an improvement. OCPs are an excellent choice for women with moderate-to-severe acne or those suffering from hirsutism and seborrhea.

Other hormonal therapies—which are not FDA approved for acne treatment—include spironolactone, cyproterone, and flutamide.²⁴ There is no evidence to support the use of finasteride or cyproterone.

Spironolactone is the most studied and has modest benefits at 100 to 150 mg/d.²² Caution is needed when using spironolactone, as gynecomastia, hyperkalemia, and agranulocytosis are potential adverse effects. It is important to closely monitor the blood pressure, chemistry, and cell count of patients taking spironolactone.

CASE Because Ms. S is sexually active and does not wish to become pregnant, she is a candidate for an OCP. You prescribe a pill containing norgestimate and EE, add a topical retinoid to her regimen, and schedule a return visit in 3 months to evaluate the effectiveness of therapy. If there is little improvement, you will recommend isotretinoin at that time.

Talk to patients about lifestyle modifications

Although the role of lifestyle changes in acne treatment is controversial, there is some evidence to suggest that these modifications are worth considering:

Glycemic load. In Western society, where the typical diet includes foods with a high glycemic index, there appears to be a higher prevalence of acne compared with regions where foods with a low glycemic index (≤55-60) are the mainstay. A low glycemic load appears to reduce both the occurrence and severity of acne.¹⁷ Thus, patients who are willing to make dietary changes should be advised to consume foods with a lower glycemic index, such as peanuts and green vegetables.

Dairy. Milk is believed to have an androgenic effect, and dairy products in general have a positive correlation with acne. Thus, a reduction in milk intake has been found to improve acne.^18,32 Stress the importance of calcium supplementation for patients whose dairy consumption is reduced or eliminated.

Fish oil. Omega-6 fatty acid, found in fish oil, has anti-inflammatory properties, and an increase in foods rich in omega-3 fatty acid (eg, salmon, sardines, walnuts) has been associated with improvement of acne.¹⁷

Probiotics. There is limited evidence for probiotics as a therapy for acne. They do appear to regulate inflammatory cytokines within the skin and to upregulate the IGF-1, both of which influence the formation of acne.^10,33

Other treatment options to consider

Injections, chemical peels, and/or laser treatments may be considered as adjunctive therapy or when standard therapies fail.

Steroid injections. This treatment regimen centers around a midpotency steroid that is diluted with normal saline and is introduced into each lesion until the lesion is distended and/or blanched. There are limited data on the use of corticosteroid injections for acne, however, and these injections are reserved for severe cases to reduce inflammation. Potential adverse effects include hyperglycemia, obesity, and Cushing traits.

Chemical peels are used to decrease both inflammatory and noninflammatory lesions, and are typically well tolerated. In one study, more than 95% of patients were satisfied with the results.^11,34

Various chemicals have been used, including alpha-hydroxyl acid (glycolic acid), beta-hydroxyl acid (salicylic acid), and Jessner’s solution, with equal efficacy.^35-38 Chemical peels can be used on patients with darker skin, but caution is required to avoid dyschromia.³⁹ Other adverse effects include dry skin, crusting, and facial erythema. More adverse effects have been reported with glycolic acid vs salicylic acid.³⁷

Laser therapies include photodynamic therapy—blue light with amino-luvanic acid—and phototherapy (blue light alone).^40-42P acnes accumulate photosensitizing porphyrins in the comedones; when the laser therapy is applied, the porphyrins absorb the light source and destroy the bacteria.

Laser treatment can also be used for scarring. Ablative laser resurfacing significantly improves acne scars; nonablative and fractional CO₂ laser modalities can also be used, with minimal downtime and no serious complications.⁴³

Other complementary therapies, including aloe vera, pyridoxine, kampo, tea tree extract, and fruit-based acids, have little or no data regarding their efficacy.

The importance of maintenance therapy

With the exception of patients whose acne was cured or who achieved remission with isotretinoin, maintenance is required once the desired appearance is reached. Without it, recurrence is likely—possibly within as little as 4 weeks.

For most patients, a topical retinoid is the only medication that should be continued. Tell patients to apply it nightly and to call for an appointment if an acne flare-up occurs.

CASE When Ms. S comes in for a follow-up visit, her acne is cleared except for a couple of lesions on her back and she is happy with the results. You advise her to continue on the OCP to avoid a recurrence but caution her that in a small percentage of cases, the acne may worsen even in women who continue to take OCPs and topicals. You agree to initiate isotretinoin if this occurs.

CORRESPONDENCE
Tam T. Nguyen, MD, San Joaquin General Hospital, 500 West Hospital Road, Suite 1103, French Camp, CA 95231; ttnguyen@sjgh.org

CASE Janis S, an otherwise healthy 19-year-old, is in your office, seeking treatment for acne. She reports she has tried various over-the-counter (OTC) creams in recent months, but has seen little improvement. The acne first appeared about 5 years ago, and her pediatrician prescribed topical adapalene and doxycycline. The treatment helped, but she says her face never fully cleared up; over the past year, the acne has gotten worse.

On examination, you find several nodules and comedones on the patient’s face, chest, and back. Ms. S confides in you that the acne—particularly on her face—kept her from going to the senior prom.

More than 80% of adolescents and adults develop acne vulgaris at some point in their lives, and in at least 15% to 20% of cases, the acne is moderate to severe.¹ Although acne typically starts in early puberty, it can continue well into adulthood.² Females typically develop acne at an earlier age than males. There are no other sex or racial differences.³

Regardless of the age at which acne develops, it has substantial psychological effects, including embarrassment, shame, depression, anxiety, social isolation—and in extreme cases, suicidal ideation.⁴ This evidence-based update will better prepare you to provide optimal medical therapy—and alleviate patients’ emotional distress—without delay.

The pathophysiology of acne vulgaris

The American Academy of Dermatology (AAD) defines acne as a “chronic inflammatory dermatosis which is notable for open and/or closed comedones (blackheads and whiteheads) and inflammatory lesions, including papules, pustules, and nodules….”⁵ The underlying etiology is best described as a cascade of events involving the pilosebaceous unit.

Normally, single keratinocytes are shed into the follicular lumen for excretion. In acne, this process is disrupted and the keratinocytes accumulate, becoming interwoven with monofilaments and lipid droplets. The lipids, cellular debris, and excessive sebum, as well as the overgrowth of Propionibacterium acnes, block the follicles;⁶ the bacterial overgrowth can generate inflammation, as well.⁷ Areas rich in sebaceous glands, such as the face, neck, chest, upper arms, and back, are the sites at which acne is most likely to develop.

Clockwise, from top: closed comedones; open comedones; pustules; and scarring.

Androgen receptors play a role
For many years, the underlying pathophysiology of acne vulgaris was thought to be lesion progression, with microcomedone formation leading to both closed and open comedones. Emerging evidence has led to a deeper understanding of acne development. Sebum is now known to have androgen receptors (nuclear transcription factor Fox O1), which are modulated by insulinlike-growth factor 1 (IGF-1) and insulin.^8,9 Research to determine whether these receptors can be influenced by diet and melanocortins is ongoing.^8,10

Evidence has also shown that inflammation around the follicles and follicular differentiation precede bacterial overgrowth,⁷ and that P acnes overgrowth exacerbates the blockage and inflammation by creating a biofilm that plugs the follicles. Inflammation is one of the main complications of acne, causing hyperpigmentation and scarring.

These factors increase the risk
There are numerous risk factors for acne, ranging from genetics to stress to certain medications (TABLE 1).¹¹ Although the exact genetic penetrance is unknown, acne often affects multiple family members;^1,12 genetics is also associated with an increase in androgens, such as that found in patients with Cushing syndrome, polycystic ovary syndrome (PCOS), and congenital adrenal hyperplasia.¹³

Emotional and physical stress can increase the risk for acne,¹⁴ with the latter often related to excessive friction on the skin caused by sweat bands or helmet strips. Cosmetics that plug the follicles are a risk factor for acne, as well.

TABLE 1
Drugs that are potential acne triggers

The patient has acne, but how severe? 

Because acne is often diagnosed clinically, there is often no need for routine testing. Nor is a bacterial culture for P acnes necessary.

If the patient has signs and symptoms suggestive of an endocrine disorder, however—eg, infertility, PCOS, or hirsutism—consider checking free testosterone, dehydroepiandrosterone sulfate (DHEA), luteinizing/follicle-stimulating hormones (LH/FSH), 17-alpha-progesterone, adrenocorticotropic hormone (ACTH), and/or dexamethasone suppression. Other indicators of a need for endocrine testing include male or female pattern balding, an abnormal menstrual cycle, acanthosis nigricans, and truncal obesity.^5,6

Numerous acne classification systems have been developed; some are based on the type of lesions (ie, comedonal, papulopustular, nodulocystic), while others also consider the number of each type of lesion and areas affected.¹⁵ In 2002, the US Food and Drug Administration (FDA) defined the components of a Global Acne Severity Scale as having 6 grades (0-5), with 0 for normal skin and 5 representing a predominance of highly inflammatory lesions with a variable number of papules/pustules and nodulocystic lesions.¹⁶

The AAD’S classification system has only 3 grades—mild, moderate, and severe—and is one of the easiest to use:

• Mild cases have few to several papules and pustules, but no nodules
• Moderate cases have more papules and pustules, with a few nodules
• Severe cases have numerous papules, pustules, and nodules.⁵

CASE Ms. S is in obvious emotional distress, and her acne needs to be treated aggressively. Because of the emotional impact and the fact that she has lesions on several body parts, her case is classified as severe (and would be even if her face had only a few lesions).

Treatment: Prevention of new lesions is paramount

Preventing new formations is a key focus of acne therapy, and patients should be advised that it may take weeks for results to be seen. Nonetheless, aggressive treatment of inflammatory lesions is necessary to prevent scarring. Because most patients have both inflammatory and bacterial lesions, it is important to use combined therapies, including topical or oral antibiotics, to treat P acnes and inflammation (TABLE 2).^13,17-23

TABLE 2
Acne classification helps guide treatment decisions^13,17-23

Topicals are the cornerstone of treatment
Retinoids and benzoyl peroxide topicals are the foundation of therapy for both comedonal and inflammatory acne,¹⁷ regardless of severity. Both are recommended by the AAD. But evidence suggests that only 55% of dermatologists and 10% of primary care providers recommend them.^19,20

Retinoids inhibit microcomedone formation and regulate follicular keratinocytes, which have anti-inflammatory properties and help to prevent the formation of new lesions. Patients should be warned that topical retinoids can cause irritation, erythema, desquamation, pruritus, and burning. To reduce the adverse effects, advise patients to start retinoid therapy slowly, at a reduced frequency (eg, every other day or every third day) and shorter contact (washing it off after one to 4 hours for a week, then increasing the contact time). When it is clear that the medication is well tolerated, the frequency and amount can be increased. Use of the topical, as tolerated, should continue as long as the potential acne problem remains.

There are 3 retinoid formulations on the market—adapalene, tretinoin, and tazarotene—all of which have been shown to be effective. Adapalene is the least irritating and the most stable, and can be safely combined with benzoyl peroxide and topical antibiotics. If tretinoin and benzoyl peroxide are used concurrently, tretinoin should be applied at night and benzoyl peroxide during the day. To reduce the risk of inactivating the topical agents, advise patients not to use other skin products in conjunction with topical therapy.

Benzoyl peroxide, which is available as a cleanser, gel, or wash, affects keratinocyte dysmaturation, P acnes, and inflammation.¹¹ The antibacterial activity is due to its oxidation. Benzoyl peroxide is available both OTC and by prescription, with concentrations ranging from 2% to 10%. Salicylic acid (2%-3%), a well-tolerated keratolytic agent, is often used with benzoyl peroxide, as well. Azelaic acid, sodium sulfacetamide, and dapsone are other topicals that have been found to be effective in treating acne.

Topical antibiotics, most commonly clindamycin 1% or sodium sulfacetamide, also affect both P acnes and inflammation,²⁴ although the exact mechanism is unknown. Available in solution or as a gel or lotion, topical antibiotics can be combined with benzoyl peroxide. Use of topical erythromycin has declined in recent years because it has a higher rate of bacterial resistance.^9,21

When to add oral antibiotics
When topical treatment does not produce the desired result or cannot be tolerated, oral antibiotics may be introduced, either as an addition or replacement. Like topicals, oral antibiotics have both antimicrobial and anti-inflammatory properties.

Tetracycline antibiotics (ie, doxycycline and minocycline) are first-line oral therapy.²¹ Minocycline has been found to be the most potent agent in this drug class; tetracycline is the least.²² Tetracyclines can cause tooth discoloration and inhibit skeletal growth, and are contraindicated for children younger than 10 years and pregnant women.

Photosensitivity is an adverse effect of tetracycline antibiotics, so patients should be advised to cover up and avoid sun exposure. Other adverse effects, particularly of minocycline, include dizziness, lupus-like syndrome, pseudotumor cerebri, skin and mucosal pigmentation, serum sickness, and hepatitis. If the patient is taking an oral contraceptive pill (OCP) concurrently for family planning, she should be advised that oral antibiotics have the potential to reduce the efficacy of the OCP.

Other oral antibiotics sometimes used to treat acne include erythromycin, trimethoprim-sulfamethoxazole, amoxicillin, and azithromycin, but data on their efficacy are limited. Erythromycin has similar potency to tetracycline, but may need to be taken 2 to 4 times a day and may cause more gastrointestinal disturbances. Cephalosporins, fluoroquinolones, aminoglycosides, chloramphenicol, sulfonamides/sulfur, and gyrase inhibitors should not be used for acne because of a lack of efficacy.⁶

Diagnostic challenge: Is it acne?

No, it isn’t. Pustules on the face, like those on the patient pictured here, are a common manifestation of acne. But facial lesions alone are not sufficient for a definitive diagnosis. In fact, the pustules that this 59-year-old woman sought treatment for were correctly diagnosed as perioral dermatitis. The tip-off? The lack of comedones and the distribution of the lesions, which were concentrated around the mouth.

Regardless of the type of oral antibiotic prescribed, it should be tried for about 3 months (8-16 weeks) and discontinued once improvement occurs. If no improvement is seen within 3 months, consider changing antibiotics due to resistance or adding antifungal therapy for Pityrosporum and Malassezia species.⁶

Initiating isotretinoin therapy: An evidence-based approach

Oral isotretinoin is the only potential cure for acne vulgaris. The cure rate is about 30% to 40% (with about 20% of patients developing a recurrence that requires retreatment within one to 3 years).²⁵

Isotretinoin is FDA approved for severe nodulocystic acne, but several organizations, including the AAD and the Global Alliance to Improve Outcomes in Acne, recommend its use for milder cases.^25,26 It is also an excellent treatment for other forms of severe acne, such as acne fulminans and acne conglobata. Accutane is no longer available, but 5 other formulations of isotretinoin are on the market.

Because isotretinoin is a category X teratogen, all providers and patients must register with iPLEDGE (www.ipledgeprogram.com), an FDA-approved mandatory risk management program. Before starting to take isotretinoin, females of childbearing age are required to undergo 2 pregnancy tests; they must also agree to use 2 forms of program-approved birth control and submit to monthly pregnancy tests.

Patients on isotretinoin also need to be monitored for depression.²⁷ Other potential adverse effects include hepatitis, hypertriglyceridemia, arthralgia, myalgias, and inflammatory bowel disease.^28,29 Dry skin and mucosa are the most common adverse effects, and patients should be advised to use moisturizers regularly.

A better dosing regimen?
The standard starting dose of isotretinoin is 0.25 to 1 mg/kg/d, divided and taken twice a day, then titrated upward monthly to a maximum daily dose of 2 mg/kg. The goal is for the total intake of isotretinoin to be 120 to 150 mg/kg. So, for example, the goal for a patient weighing 60 kg might be a cumulative intake of 7200 mg (120 mg/kg × 60 kg), taken in doses of 20 mg BID (40 mg/d) for 180 days.

The medication should be taken with food (especially with fatty food) for better absorption. Treatment duration has typically been 16 to 32 weeks, with an average of 20 weeks, with the daily dose lowered in patients requiring treatment for a longer period of time. Continuous use of isotretinoin is more effective than taking it intermittently.²⁶

Lower dosages? While that standard regimen has been adequate in the management of acne vulgaris, emerging evidence suggests that dosages of isotretinoin as low as 5 mg/d are equally effective and have significantly fewer adverse effects.³⁰ Relapse continues to be a problem. Risk factors for relapse include a macrocomedonal pattern of acne, smoking, and age, with patients <14 years and >25 years at higher risk.³⁰ While lower dosing was previously thought to be associated with greater risk of relapse, this appears to be related less to the cumulative dose of 120 to 150 mg/kg and more to the duration of sebaceous gland suppression.³⁰

Based on the latest evidence, important changes in isotretinoin administration are called for—specifically, using a much lower dose (0.25-0.5 mg/kg, divided into 2 daily doses) for a longer period of time.³⁰ While the traditional dosing generally requires a 3- to 5-month course of treatment, the lower dosing can take 6 to 8 months.

Who's a candidate for hormonal therapy?

Any hormone that has antiandrogenic properties can have a beneficial effect on acne.

The most common hormonal therapy is an estrogen-progestin combination OCP.^23,31 Progesterone-only OCPs should not be used as they can worsen acne.

In theory, any OCP that contains estrogen can work because of its androgenic properties. The estrogen appears to suppress sebaceous gland activity. OCPs with FDA approval for the treatment of acne include Estrostep Fe (norethindrone/ethinyl estradiol [EE]), Ortho Tricyclen (norgestimate/EE), and Yasmin and Beyaz (drospirenone/EE). With any OCP, the effect is gradual, and it can take 3 to 4 months for patients to see an improvement. OCPs are an excellent choice for women with moderate-to-severe acne or those suffering from hirsutism and seborrhea.

Other hormonal therapies—which are not FDA approved for acne treatment—include spironolactone, cyproterone, and flutamide.²⁴ There is no evidence to support the use of finasteride or cyproterone.

Spironolactone is the most studied and has modest benefits at 100 to 150 mg/d.²² Caution is needed when using spironolactone, as gynecomastia, hyperkalemia, and agranulocytosis are potential adverse effects. It is important to closely monitor the blood pressure, chemistry, and cell count of patients taking spironolactone.

CASE Because Ms. S is sexually active and does not wish to become pregnant, she is a candidate for an OCP. You prescribe a pill containing norgestimate and EE, add a topical retinoid to her regimen, and schedule a return visit in 3 months to evaluate the effectiveness of therapy. If there is little improvement, you will recommend isotretinoin at that time.

Talk to patients about lifestyle modifications

Although the role of lifestyle changes in acne treatment is controversial, there is some evidence to suggest that these modifications are worth considering:

Glycemic load. In Western society, where the typical diet includes foods with a high glycemic index, there appears to be a higher prevalence of acne compared with regions where foods with a low glycemic index (≤55-60) are the mainstay. A low glycemic load appears to reduce both the occurrence and severity of acne.¹⁷ Thus, patients who are willing to make dietary changes should be advised to consume foods with a lower glycemic index, such as peanuts and green vegetables.

Dairy. Milk is believed to have an androgenic effect, and dairy products in general have a positive correlation with acne. Thus, a reduction in milk intake has been found to improve acne.^18,32 Stress the importance of calcium supplementation for patients whose dairy consumption is reduced or eliminated.

Fish oil. Omega-6 fatty acid, found in fish oil, has anti-inflammatory properties, and an increase in foods rich in omega-3 fatty acid (eg, salmon, sardines, walnuts) has been associated with improvement of acne.¹⁷

Probiotics. There is limited evidence for probiotics as a therapy for acne. They do appear to regulate inflammatory cytokines within the skin and to upregulate the IGF-1, both of which influence the formation of acne.^10,33

Other treatment options to consider

Injections, chemical peels, and/or laser treatments may be considered as adjunctive therapy or when standard therapies fail.

Steroid injections. This treatment regimen centers around a midpotency steroid that is diluted with normal saline and is introduced into each lesion until the lesion is distended and/or blanched. There are limited data on the use of corticosteroid injections for acne, however, and these injections are reserved for severe cases to reduce inflammation. Potential adverse effects include hyperglycemia, obesity, and Cushing traits.

Chemical peels are used to decrease both inflammatory and noninflammatory lesions, and are typically well tolerated. In one study, more than 95% of patients were satisfied with the results.^11,34

Various chemicals have been used, including alpha-hydroxyl acid (glycolic acid), beta-hydroxyl acid (salicylic acid), and Jessner’s solution, with equal efficacy.^35-38 Chemical peels can be used on patients with darker skin, but caution is required to avoid dyschromia.³⁹ Other adverse effects include dry skin, crusting, and facial erythema. More adverse effects have been reported with glycolic acid vs salicylic acid.³⁷

Laser therapies include photodynamic therapy—blue light with amino-luvanic acid—and phototherapy (blue light alone).^40-42P acnes accumulate photosensitizing porphyrins in the comedones; when the laser therapy is applied, the porphyrins absorb the light source and destroy the bacteria.

Laser treatment can also be used for scarring. Ablative laser resurfacing significantly improves acne scars; nonablative and fractional CO₂ laser modalities can also be used, with minimal downtime and no serious complications.⁴³

Other complementary therapies, including aloe vera, pyridoxine, kampo, tea tree extract, and fruit-based acids, have little or no data regarding their efficacy.

The importance of maintenance therapy

With the exception of patients whose acne was cured or who achieved remission with isotretinoin, maintenance is required once the desired appearance is reached. Without it, recurrence is likely—possibly within as little as 4 weeks.

For most patients, a topical retinoid is the only medication that should be continued. Tell patients to apply it nightly and to call for an appointment if an acne flare-up occurs.

CASE When Ms. S comes in for a follow-up visit, her acne is cleared except for a couple of lesions on her back and she is happy with the results. You advise her to continue on the OCP to avoid a recurrence but caution her that in a small percentage of cases, the acne may worsen even in women who continue to take OCPs and topicals. You agree to initiate isotretinoin if this occurs.

CORRESPONDENCE
Tam T. Nguyen, MD, San Joaquin General Hospital, 500 West Hospital Road, Suite 1103, French Camp, CA 95231; ttnguyen@sjgh.org