Chapter 112. Acne Vulgaris

A 16-year-old boy (Figure 112-1) with severe nodulocystic acne and scarring presents for treatment. After trying oral antibiotics, topical retinoids, and topical benzyl peroxide with no significant benefit, the patient and his mother request isotretinoin (Accutane). After 4 months of isotretinoin, the nodules and cysts cleared and there remained only a few papules (Figure 112-2). He is much happier and more confident about his appearance. The skin cleared fully after the last month of isotretinoin.

Acne is an obstructive and inflammatory disease of the pilosebaceous unit predominantly found on the face of adolescents. However, it can occur at any age and often involves the trunk in addition to the face.

Acne vulgaris affects more than 80% of teenagers, and persists beyond the age of 25 years in 3% of men and 12% of women.1

The four most important steps in acne pathogenesis:

1. Sebum overproduction related to androgenic hormones and genetics.

2. Abnormal desquamation of the follicular epithelium (keratin plugging).

3. Propionibacterium acnes proliferation.

4. Follicular obstruction, which can lead to inflammation and follicular disruption.

Neonatal acne is thought to be related to maternal hormones and is temporary (Figure 112-3).

Acne can be precipitated by mechanical pressure as with a helmet strap (Figure 112-4) and medications such as phenytoin and lithium (Figure 112-5).

There are some studies that suggest that consumption of large quantities of milk (especially skim milk) increase the risk for acne in teenagers.2

Clinical Features

Morphology of acne includes comedones, papules, pustules, nodules, and cysts.

• Obstructive acne = comedonal acne = noninflammatory acne and consists of only comedones (Figure 112-6).
• Open comedones are blackheads and closed comedones are called whiteheads and look like small papules.
• Inflammatory acne has papules, pustules, nodules, and cysts in addition to comedones (Figure 112-5).

Typical Distribution

Face, back, chest, and neck.

Laboratory Studies

None unless you suspect androgen excess and/or polycystic ovarian syndrome (PCOS).3 SOR A Obtain testosterone and DHEA-S levels if you suspect androgen excess and/or PCOS.

Consider follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels if you suspect PCOS.

• Acne conglobata is an uncommon and unusually severe form of acne characterized by multiple comedones, cysts, sinus tracks, and abscesses. The inflammatory lesions and scars can lead to significant disfigurement.4 Sinus tracks can form with multiple openings that drain foul-smelling purulent material (Figures 112-7, 112-8 and 112-9). The comedones and nodules are usually found on the chest, the shoulders, the back, the buttocks, and the face. In some cases acne conglobata is part of a follicular occlusion triad including hidradenitis and dissecting cellulitis of the scalp (Figure 112-9).
• Acne fulminans is characterized by sudden onset ulcerative crusting cystic acne, mostly on the chest and back (Figures 112-10 and 112-11).5 Fever, malaise, nausea, arthralgia, myalgia, and weight loss are common. Leukocytosis and elevated erythrocyte sedimentation rate are usually found. There may also be focal osteolytic lesions. The term acne fulminans may also be used in cases of severe aggravation of acne without systemic features.5
• Rosacea can resemble acne by having papules and pustules on the face. It is usually seen in older adults with prominent erythema and telangiectasias. Rosacea does not include comedones and may have ocular or nasal manifestations (Chapter 113, Rosacea). Rosacea fulminans or pyoderma faciale has features of severe acne and rosacea (Figure 112-12).
• Folliculitis on the back may be confused with acne. Look for hairs centrally located in the inflammatory papules of folliculitis to help distinguish it from acne. Acne on the back usually accompanies acne on the face as well (Chapter 117, Folliculitis).
• Acne keloidalis nuchae consists of papules, pustules, nodules, and keloidal tissue found at the posterior hairline. It is most often seen in men of color after shaving the hair at the nape of the neck (Chapter 114, Pseudofolliculitis and Acne Keloidalis Nuchae).
• Actinic comedones (blackheads) are related to sun exposure and are seen later in life (Figure 112-13).

Treatment is based on type of acne and severity. Categories to choose from are topical retinoids, topical antimicrobials, systemic antimicrobials, hormonal therapy, oral isotretinoin, and injection therapy.

Medications for Acne Therapy

In a review of 250 comparisons, the Agency for Healthcare Research and Quality found 14 had evidence of level A.6 These comparisons demonstrated the efficacy over vehicle or placebo control of topical clindamycin, topical erythromycin, benzoyl peroxide, topical tretinoin, oral tetracycline, and norgestimate/ethinyl estradiol.4 Level A conclusions demonstrating equivalence include: Benzoyl peroxide at various strengths was equally efficacious in mild/moderate acne; adapalene and tretinoin were equally efficacious.6 SOR A

Topical

• Benzoyl peroxide—Antimicrobial effect (gel, cream, lotion) (2.5%, 5%, 10%) 10% causes more irritation and is not more effective.1 SOR A
• Topical antibiotics—Clindamycin and erythromycin are the mainstays of treatment.
• Erythromycin—Solution, gel.3 SOR A
• Clindamycin—Solution, gel, lotion.3 SOR A
• Benzamycin gel—Erythromycin 3%, benzoyl peroxide 5%.3 SOR A
• BenzaClin gel—Clindamycin 1%, benzoyl peroxide 5%.3 SOR A
• Dapsone 5% gel.7 SOR B

Retinoids:

• Tretinoin (Retin-A) gel, cream, liquid, micronized.1 SOR A
• Adapalene gel—Less irritating than tretinoin.1 SOR A
• Tazarotene—Strongest topical retinoid with greatest risk of irritation.8 SOR A

Topical retinoids will often result in skin irritation during the first 2 to 3 months of treatment, but new systematic reviews do not demonstrate that they worsen acne lesion counts during the initial period of use.2

• Azelaic acid—Useful to treat spotty hyperpigmentation and acne (Figure 112-14).3 SOR B

Systemic

• Oral antibiotics.
  • Tetracycline 500 mg qd-bid—Inexpensive, absorbed best on an empty stomach.3 SOR A
  • Doxycycline 40 to 100 mg qd bid—Inexpensive, well tolerated, can take with food and increases sun sensitivity.3 SOR A
  • Minocycline 50 to 100 mg qd bid—Expensive, not proven to be better than other systemic antibiotics including tetracycline.3,9 SOR A
  • Erythromycin 250 to 500 mg bid—Inexpensive, frequent gastrointestinal (GI) disturbance but can be used in pregnancy.3 SOR A
  • Trimethoprim/sulfamethoxazole DS bid—Effective but risk of Stevens-Johnson syndrome is real. Reserve for short courses in particularly severe and resistant cases.3 SOR A

Oral azithromycin has been prescribed in pulse dosing for acne in a number of small poorly done studies and has not been found to be better than oral doxycyline.10

• Isotretinoin (Accutane) is the most powerful treatment for acne. It is especially useful for cystic and scarring acne that has not responded to other therapies.3 SOR A Dosed at approximately 1 mg/kg per day for 5 months. Women of childbearing age must use two forms of contraception. Monitor for depression.
• The U.S. Food and Drug Administration requires that prescribers of isotretinoin, patients who take isotretinoin, and pharmacists who dispense isotretinoin all must register with the iPLEDGE system (www.ipledgeprogram.com).
• Hormonal treatments:
  • Oral contraceptives only for females—Choose ones with low androgenic effect.3 SOR A FDA-approved oral contraceptives are Ortho Tri-Cyclen, Yaz, and Estrostep. Other oral contraceptives with similar formulations also help acne in women even though these have not received FDA approval for this indication. Note Yaz and Yasmin have progestin drospirenone, which is derived from 17α-spirolactone. It shares an antiandrogenic effect with spironolactone.
  • Spironolactone may be used for adult women when other therapies fail.3,11,12 This may be especially useful if the patient has hirsutism. Standard dosing is 50 to 200 mg/day. May start with 25 mg bid and monitor for hyperkalemia. The risk of hyperkalemia increases with a higher dose. Titrate up as needed and tolerated.3 SOR B A recent systematic review failed to show a benefit for spironolactone in acne even though it was found to decrease hirsutism.13
  • One small prospective study of 27 women with severe papular and nodulocystic acne used a combination of EE/DRSP (Yasmin) and spironolactone 100 mg daily. Eighty-five percent of subjects were entirely clear of acne lesions or had excellent improvement and there was no significant elevation of serum potassium.14

Complementary and Alternative Therapy

Tea tree oil 5% gel.15 SOR B

• Steroid injection therapy
• For painful nodules and cysts. SOR C Be careful to avoid producing skin atrophy.

• Dilute 0.1 cc of 10 mg/cc triamcinolone acetonide (Kenalog) with 0.4 cc of sterile saline for a 2 mg/cc suspension.
• Inject 0.1 cc with a 1-cc tuberculin syringe into each nodule using a 30-gauge needle (Figure 112-15).

Acne Therapy by Severity

Comedonal acne (Figure 112-6).

• Topical retinoid or azelaic acid.
• No need for antibiotics or antimicrobials—Do not need to kill P. acnes.

Mild papulopustular

• Topical antibiotics and benzoyl peroxide.
• Topical retinoid or azelaic acid.
• May add oral antibiotics if topical agents are not working.

Papulopustular or nodulocystic acne—moderate to severe—inflammatory

• Topical antibiotic, benzoyl peroxide, and oral antibiotic.
• Oral antibiotics are often essential at this stage.
• Topical retinoid or azelaic acid.
• Steroid injection therapy—For painful nodules and cysts.

Severe cystic or scarring acne

• Isotretinoin if there are no contraindications.
• Steroid injection therapy—For painful nodules and cysts.

Acne fulminans (Figures 112-9, 112-10, 112-11)

• Start with systemic steroids (prednisone 40 to 60 mg/day—approximately 1 mg/kg per day).16 SOR C
• Systemic steroid treatment rapidly controls the skin lesions and systemic symptoms. The duration of steroid treatment in one Finnish series was 2 to 4 months to avoid relapses.16 SOR C
• Therapy with isotretinoin, antibiotics, or both was often combined with steroids, but the role of these agents is still uncertain.16 SOR C
• One British series used oral prednisolone 0.5 to 1 mg/kg daily for 4 to 6 weeks (thereafter slowly reduced to zero).17 SOR C
• Oral isotretinoin was added to the regimen at the fourth week, initially at 0.5 mg/kg daily and gradually increased to achieve complete clearance.17 SOR C
• Consider introducing isotretinoin at approximately 4 weeks into the oral prednisone if there are no contraindications. SOR C

Acne conglobata and pyoderma faciale may be treated like acne fulminans but the course of oral prednisone does not need to be as long. SOR C

Combination Therapies

• Combination therapy with multiple topical agents can be more effective than single agents.3 SOR B
• Topical retinoids and topical antibiotics are more effective when used in combination than when either are used alone.3 SOR B
• Benzoyl peroxide and topical antibiotics used in combination are effective treatment for acne by helping to minimize antibiotic resistance.3 SOR B
• The adjunctive use of clindamycin/benzoyl peroxide gel with tazarotene cream promotes greater efficacy and may also enhance tolerability.18
• Combination therapy with topical retinoids and oral antibiotics can be helpful at the start of acne therapy. However, maintenance therapy with combination tazarotene and minocycline therapy showed a trend for greater efficacy but no statistical significance vs. tazarotene alone.19

Medication Cost

The most affordable medications for acne include topical benzoyl peroxide, erythromycin, clindamycin, and oral tetracycline and doxycycline. The most expensive acne medications are the newest brand-name combination products of existing topical medication. These medications are convenient for those with insurance that covers them (Epiduo contains benzoyl peroxide and adapalene; Ziana contains clindamycin and tretinoin).

Newer Expensive Modes of Therapy

Intense pulsed light and photodynamic therapy (PDT) use lasers, special lights, and topical chemicals to treat acne.20-22 These therapies are very expensive and the data do not suggest that these should be first-line therapies at this time. Light and laser treatments have been shown to be of short-term benefit if patients can afford therapy and tolerate some discomfort. These therapies have not been shown to be better than simple topical treatments.2

One comparative trial demonstrated that PDT was less effective than topical adapalene in the short-term reduction of inflammatory lesions.2

Isotretinoin requires monthly follow-up visits but other therapies can be monitored every few months at first and then once to twice a year. Keep in mind that many treatments for acne take months to work, so quick follow-up visits may be disappointing.

Adherence with medication regimens is crucial to the success of the therapy. Adequate face washing twice a day is sufficient. Do not scrub the face with abrasive physical or chemical agents. If benzoyl peroxide is not being used as a leave-on product, it can be purchased to use for face washing.

Patient Resources

• PubMed Health has a good patient education information—http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001876/.

Provider Resources

• Usatine R, Pfenninger J, Stulberg D, Small R. Dermatologic and Cosmetic Procedures in Office Practice. Philadelphia: Elsevier; 2012—Covers how to do acne surgery, steroid injections for acne, chemical peels, PDT and laser treatment for acne. It is also available as an app: www.usatinemedia.com.