US Pharm. 2006;31(9):HS-3-HS-5.

Acne vulgaris is the severe form of a common skin disorder characterized by noninflammatory follicular papules, or comedones, and by inflammatory follicular papules and nodules. It affects areas containing the largest oil glands, including the face, the upper part of the chest, and the back. In the United States, acne affects 85% to 100% of people at some point in their lives. Some adult women experience mild to moderate acne due to hormonal changes associated with pregnancy, their menstrual cycle, or starting or stopping birth control pills.1

The pathogenesis of acne is multifactorial. It is caused by a disorder of the oil glands that results in clogged pores and outbreaks of lesions commonly known as pimples. It tends to last longer in young females than in males, and it generally disappears by age 30. Although it is not a serious health threat, severe acne can be painful and may cause permanent scarring, which can be upsetting for young adult patients. An estimated $100 million is spent annually on OTC products to treat acne and reduce the pain, scarring, and associated emotional distress.2 A study of British teenagers indicated that 39% of those with acne claimed that they avoided going to school because of embarrassment, 55% stated that acne prevented them from having a boyfriend or girlfriend, and 32% indicated that acne kept them from making friends.3 Fortunately, with proper treatment, acne can be controlled, causing less scarring.

Various Types of Acne Lesions
There are several types of lesions associated with acne. Microcomedones are enlarged hair follicles plugged with oil and bacteria. They are the smallest type of lesion and cannot be seen by the naked eye. Whiteheads or closed comedones are clogged follicles that stay beneath the skin. Whiteheads usually appear as round, white bumps that are roughly 1 to 2 mm in diameter. Blackhead comedones are plugged follicles that reach the surface of the skin and are dark in appearance. Papules are inflamed lesions that appear as small, pink bumps on the skin. Pimples, which are inflamed, pus-filled lesions, are red at the base. Finally, cysts and nodules are large, inflamed, pus-filled lesions that are deeply lodged and capable of draining, causing pain and scarring.2

Underlying Causes
Acne is a disorder of the skin's oil glands, and an external cause is seldom identifiable. Oil glands make a substance called sebum, which normally rises up through a hair follicle and empties onto the skin surface. The precise cause of acne in newborns is not known, but some researchers speculate that it may be due to the transfer of hormones from the mother through the placenta or a result of acne-causing medication (see below) that the mother may have been taking. During adolescence, hormones called androgens become active and stimulate oil glands in the skin, increasing oil production. This, in turn, clogs pores, causing pimples and blackheads. Hormonal changes that occur during a menstrual period or when starting or stopping birth control pills can also cause an acne flare-up, although certain birth control pills may be prescribed as a treatment for acne. If the comedones remain intact and do not rupture, they can progress into open comedones (whiteheads) or closed comedones (blackheads). When comedones rupture, an inflammatory reaction occurs and can spread into the surrounding tissue. Papules, pustules, cysts, and nodules are all forms of inflammatory lesions.4

Risk Factors
Risk factors for acne include:
• Heredity or genetic factors;
• Hormonal changes associated with adolescence, pregnancy, or menstruation (acne tends
to flare up two to seven days before menstruation begins);

• Certain medications, such as corticosteroids, androgens, oral contraceptives, lithium, isoniazid, phenytoin, and phenobarbital;
• Congenital adrenal hyperplasia and polycystic ovary syndrome;
• Some cosmetic agents and hair pomades;
• Sweating and friction, such as from headbands, back packs, bicycle helmets, or tight collars; and
• Squeezing and picking at comedones.

Diagnosis
Four key factors are responsible for the development of an acne lesion. These factors are follicular epidermal hyperproliferation, excess sebum, the presence and activity of Propionibacterium acnes (the bacterial strain associated with acne), and inflammation. General practitioners and pediatricians do not have difficulty diagnosing acne, due to its particular appearance. Upon careful examination of the face and body, the practitioner looks for lesions and scars, assesses the size of the pimples, and determines whether pimples are inflamed. Mild and moderate forms of acne can be treated by general practitioners or pediatricians, but severe cases of acne require referral to a dermatologist or a skin disease specialist. Clinicians normally ask for a complete medical history, including skin care, cosmetic use, factors that trigger flare-ups, medication use, occupational and environmental exposures, and prior treatment.5

Treatment Options
There are three important considerations in the treatment of acne: preventing scarring, reducing the number of painful lesions, and minimizing the emotional distress related to the condition. One aspect of treatment is skin care, which involves washing the affected area no more than one to two times per day with a mild, nondrying soap. The first-choice agent for acne treatment is generally either benzoyl peroxide or a class of drugs known as retinoids. These are designed to wear away the top layer of skin as well as to reduce abnormal clumping of cells in the follicles, oil and bacteria production, and inflammation. Alternative remedies for mild acne, such as herbs and homeopathy, are popular with many patients. Regardless of whether medications or alternative remedies are used, it typically takes six to eight weeks of treatment before improvement is noticeable.4,5

Topical Medications: Available by prescription and OTC, topical medications (e.g., gels, lotions, creams, soaps, pads) include benzoyl peroxide, retinoids, and antibiotics. They all work by killing bacteria, reducing inflammation, and unclogging pores. Benzoyl peroxide should not be combined with retinoids and has to be applied to small areas of the skin before it is applied to the face safely. It should be used once or twice a day to prevent allergic contact dermatitis.

Retinoids, such as tretinoin, are comedolytic and anti-inflammatory, and they should be used in patients with significant numbers of both open and closed comedones, as well as papules and pustules. Their side effects include redness, peeling, and photosensitivity. Most retinoids are applied at night and should not be applied at the same time as benzoyl peroxide. Topical retinoids should not be used during pregnancy, as they may harm the fetus.

Available by prescription, topical antibiotics, such as clindamycin or erythromycin, may be used to treat mild to moderate acne. Many patients have had success with combinations of topical medications, such as benzoyl peroxide and clindamycin.

Oral Medications: Oral antibiotics either alone or in addition to topical medications are the mainstay of treatment for moderate to severe acne. Commonly prescribed oral antibiotics include doxycycline, minocycline, and tetracycline. Oral antibiotics should not be used during pregnancy or by those younger than 9 years.

An oral retinoid, isotretinoin reduces the size of oil glands and lowers sebum production by 70%. It is usually prescribed for patients with severe inflammatory acne that does not improve with other medications. Isotretinoin is taken twice a day for 20 weeks at a dose of 0.5 mg/kg/day until a cumulative dose of 120 to 150 mg/kg is reached. Iso­tretinoin is in category X and must not be used during pregnancy.6 To reduce the risk of birth defects, the iPledge program was launched in March 2006, based on the recommendation of an FDA advisory committee. This program is designed to protect patients from harm, but it is controversial, as many dermatologists believe that it reduces access to the drug.

Certain oral contraceptives used in addition to acne medications have worked well in treating acne.

 

Surgical Care

To improve the appearance of the skin in patients with severe acne scars, surgical procedures may be required. Skin-resurfacing techniques, such as dermabrasion (a procedure that uses a rapidly rotating brush to remove acne scars or pits), chemical peeling (a chemical solution is applied to the skin, causing it to blister and eventually peel off), punch grafting (a method in which the surgeon punches a hole in the skin, removes the scar, and replaces it with a small plug of new skin), and collagen implantation have been used by dermatologic surgeons to correct deep acne scars.

Phototherapy and Laser Therapy
Phototherapy using red light or blue light and photodynamic therapy are being assessed.7 The utility of some laser treatments in the management of acne is also being evaluated. New research shows that the laser is a safe and effective treatment for facial inflammatory acne. It reduces inflammatory facial acne lesions, has few side effects, and appears to work even for patients with dark skin.8

Nutrition and Acne
People with acne may complain that certain drinks and foods (particularly nuts) worsen their symptoms. Although it is not yet scientifically proved that there is a connection between diet and acne, people with this skin condition should avoid foods that appear to aggravate their symptoms.

Zinc is a trace mineral recommended frequently for acne treatment. It helps with wound healing and is essential for cell division and growth. It assists in proper functioning of the hormone insulin and the formation of cellular DNA. This mineral also has a role in more than 300 enzymes in the body. It synthesizes protein and protects the body from free radicals. It also triggers the birth of new white blood cells. Certain topical medications, including erythromycin ointment, may contain zinc oxide. It is possible that the zinc contained in the ointment may contribute to the product's effectiveness.9

Some herbs, such as calendula, German chamomile, witch hazel, licorice root, and flaxseed, have anti-inflammatory properties that may be helpful in the treatment of skin conditions, including acne. In addition, turmeric, basil, and neem have been reported to be extremely effective in treating acne, eczema, and other skin diseases. Plant products such as tea tree oil (Melaleuca alternifolia) contain antimicrobial substances that may help eliminate P. acnes, thereby potentially reducing inflammation associated with the skin condition.10 One study compared the effectiveness of tea tree oil gel with benzoyl peroxide lotion in 119 people with mild to moderate acne. Patients in both treatment groups showed a significant reduction in the number of inflamed and noninflamed lesions over a three-month period. Seventy-nine percent of the benzoyl peroxide group compared to 44% of the tea tree oil group reported side effects, including stinging, itching, burning, and dryness. A laboratory study also found that tea tree oil, as well as some of its individual components, effectively slows the growth of P. acnes.11

Biofeedback and Cognitive Therapy
Because emotional stress, particularly in young adults, can worsen acne, it is possible that relaxation therapies such as biofeedback, together with cognitive therapy, improve acne symptoms. Techniques such as biofeedback can give an individual control over certain internal bodily processes that normally occur involuntarily, such as heart rate and muscle tension. During biofeedback training and cognitive therapy, an individual can visualize and understand the bodily changes that occur when he or she relaxes. Experimental research has shown that this process, in addition to other treatments, will speed the healing of acne and other skin diseases.

Pregnancy
Treating acne during pregnancy is a challenge. Pregnant women should avoid all retinoids (oral and topical), including iso­tretinoin, and the antibiotics tetracycline, minocycline, and doxycycline, because they can be harmful to the fetus. Benzoyl peroxide should be avoided during pregnancy if other options are available. The antibiotic erythromycin (in both topical and oral forms) is safe to use during pregnancy.

References

1. Krowchuk DP. Treating acne: a practical guide. Med Clin North Am. 2000;84:811-828.

2. American Academy of Dermatology (AAD). Acne. 1987. Available at:  www.aad.org. Accessed October 12, 2001.

3. Jancin B. Teens with acne cite shame, embarrassment about skin. Skin and Allergy News. January 2004: 28.

4. Shaw JC, White LE. Persistent acne in adult women. Arch Dermatol. 2001;137:1252-1253.

5. Zouboulis CC. Is acne vulgaris a genuine inflammatory disease? Dermatology. 2001;203:277-279.

6. Jick SS, Kremers HM, Vasilakis-Scaramozza C. Isotretinoin use and risk of depression, psychotic symptoms, suicide, and attempted suicide. Arch Dermatol. 2000;136:1231-1236.

7. Papageorgiou P, Katsambas A, Chu A. Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris. Br J Dermatol. 2000;142:973-978.

8. Cunliffe WJ, Goulden V. Phototherapy and acne vulgaris. Br J Dermatol.2000;142:855-856.

9. Meynadier J. Efficacy and safety study of two zinc gluconate regimens in the treatment of inflammatory acne. Eur J Dermatol. 2000;10:269-273.

10. Ernst E, Huntley A. Tea tree oil: a systematic review of randomized clinical trials. Forsch Komplementärmed Klass Naturheilkd. 2000;7:17-20.

11. Bassett IB, Pannowitz DL, Barnetson RS. A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne. Med J Aust. 1990;153:455-458.

To comment on this article, contact editor@uspharmacist.com.