US Pharm. 2006;4:34-42.      

Acne vulgaris is the most common skin disease, affecting about 17 million Americans in all age-groups and ethnic backgrounds.1 Although the condition can occur at any age, it affects primarily teenagers and young adults between the ages of 12 and 24; nearly 85% of people in this age-group get acne. While most cases resolve by age 30, for some people, the condition persists into middle age. 1

Characterized by noninflammatory follicular papules and, in its more severe forms, by inflammatory papules, pustules, and nodules, acne occurs when the pores of the skin become clogged with oil, dead skin cells, and bacteria. The condition typically affects the areas of skin with the densest population of sebaceous follicles, including the face, upper chest, and back. Although not curable, early treatment and regular preventive skin care can minimize mild to moderate cases, and prescription medications can effectively treat acne in even its most severe forms.

The Skin
The skin is the largest organ of the body, forming a protective barrier against harmful agents in the environment. Functions of the skin include helping to maintain proper body temperature through the evaporation of sweat and the insulation of fat in the subcutaneous tissue, gathering sensory information from the environment, and facilitating calcium homeostasis through vitamin D synthesis.2 Melanin, a pigment produced in the skin, protects cell nuclear structures from damage by ultraviolet radiation.2

The skin comprises three layers: the epidermis, the dermis, and subcutaneous tissue (figure 1). The epidermis consists of multiple layers known as the stratified epithelium and renews itself continuously by cell division in its deepest layer, the basal layer. Cells produced by cell division undergo a process called keratinization, which deposits the fibrous protein keratin and causes the cells on the surface of the skin to form a horny layer called the stratum corneum, the outermost layer of the epidermis. The stratum corneum consists of flattened keratinized cells devoid of nucleic and cytoplasmic organelles. Adjacent cells overlap at their margins, causing cells to lock together with intercellular lipid and to form a very effective barrier that helps prevent the rapid loss of water. While the thickness of the stratum corneum varies from region to region of the body depending upon the amount of friction from contact with other surfaces, the thickest areas are found over the palms of the hands and the soles of the feet.2




The dermis, located below the epidermis, contains small blood vessels that provide nutrition to skin cells and nerves involved in sensory transmission and to specialized structures, such as hair follicles, sebaceous glands, and sweat glands.2 Sebaceous glands are attached to the follicles and are found on all areas of the skin except the palms of the hands and soles and dorsa of the feet. Most sebaceous glands open into hair follicles, known as the pilosebaceous units , while others open directly to the skin surface on the eyelids, prepuce, female
genitalia, and areola.2


The subcutaneous layer is below the dermis and contains larger nerves and blood vessels that regulate body temperature by conducting heat from the internal organs of the body to the surface of the skin. Maximal vasodilatation of all skin blood vessels can increase blood flow to the skin up to seven times the normal volume. The skin's circulatory system serves as a large blood reservoir, representing 5% to 10% of the body's total blood volume. Under circumstances of circulatory stress (e.g., hemorrhage), vasoconstriction forces this blood into the general circulation. This layer also contains subcutaneous fat that facilitates thermoregulation by insulating tissues beneath the skin.2

Pathophysiology of Acne
Acne is described as a disease of the pilosebaceous units (figure 2), which are most numerous on the face, upper back, and chest. Sebaceous glands produce an oily substance called sebum that normally empties onto the surface of the skin through the opening of a follicle known as a pore. Keratin-producing cells called keratinocytes line the follicle.1 When acne occurs, the hair, sebum, and keratinocytes that line the pilosebaceous unit form a plug that does not allow sebum to flow to the surface. These plugs allow Propionibacterium acnes, bacteria that normally live on the surface of the skin, to grow in the plugged follicles. The presence of P. acnes attracts white bloods cells and causes inflammation, characterized by swelling, redness, heat, and pain. Inflammation leads to a variety of lesions known as pimples (figure 3).1




An enlarged, plugged follicle forms the basic acne lesion, known as a comedo. If the plugged follicle or comedo stays beneath the skin, it produces a white bump called a whitehead , or a closed comedo. A comedo that reaches the surface of the skin is called an open comedo or a blackhead, because the sebum turns black when exposed to air.




Other acne lesions include papules, pustules, macules, nodules, and cysts.1 A papule is formed by a cellular reaction to the process of comedo formation. A papule is a small (5 mm or less), solid lesion slightly elevated above the surface of the skin. Papules may be so small that they are almost invisible, but may give the skin a "sandpaper" feel.3 A dome-shaped, fragile lesion containing pus is called a pustule. Pus is a combination of white blood cells, dead skin cells, and bacteria. Pustules can heal without leaving scars or can progress to cystic forms. A macule is a temporary flat, red spot left by a healed acne lesion. Macules can persist for days or weeks and contribute to the inflamed appearance of acne. A nodule is a solid, dome-shaped, or irregularly shaped lesion that can be painful. Unlike pustules, nodules are characterized by inflammation, extend into the deeper layers of the skin, and may cause tissue destruction resulting in scarring. 3 Cysts are sac-like lesions containing liquid or semiliquid material of dead cells, white blood cells, and bacteria. Cysts are larger than pustules, extend into the deeper layers of the skin, and can be very painful and often cause scarring. Cysts are a severe form of acne that is resistant to most treatment.3

Factors Contributing to Acne
While the exact cause of acne is unknown, contributing factors have been identified. Fluctuations in hormones are known to worsen acne. Increased levels of androgens during puberty in males and females cause sebaceous glands to enlarge and produce more sebum. In females, hormonal changes before menstruation or during pregnancy can worsen the condition, and initiating or discontinuing the use of birth control pills can also contribute. Additionally, a family history of acne increases the likelihood of acne.4

A number of prescription medications, including anticonvulsants, anti-inflammatory corticosteroids, and immunosuppressants are known to cause or worsen acne (table 1). Pressure on the skin from athletic equipment, backpacks, or tight clothing can make acne worse. Greasy cosmetics or grease from the work environment (e.g., from cooking or working on machinery) can also aggravate the condition, and environmental irritants, such as pollution and high humidity, are associated with acne flare-ups. Although not considered a cause of acne, stress can exacerbate acne. In addition, hard scrubbing irritates the skin and triggers inflammation, while squeezing or picking blemishes pushes bacteria from the surface of the skin into the pilosebaceous units and contributes to comedo formation.1




There are many misconceptions about causes of acne. Although chocolate and greasy foods are often blamed for causing acne, there is little evidence that foods have much effect on the condition. Another common misconception is that dirty skin causes acne. Dirt does not contribute to lesion formation.1

Acne Treatment
Over-the-counter (OTC) and prescription medications are used both topically and orally to treat acne. Treatment goals include healing existing lesions, preventing scarring and the formation of new lesions, and minimizing psychological stress and embarrassment. Different factors that contribute to lesion formation are targeted to reduce sebum production, inflammation, and abnormal clumping of cells in follicles involved in plug formation and to control bacterial growth. 5
OTC medications: Topical OTC products are often used for mild to moderate acne. Benzoyl peroxide, which kills P. acnes and may reduce sebum production, has been the mainstay of acne prevention for years. Benzoyl peroxide is available in strengths ranging from 2.5% to 10% and in a variety of preparations, including creams, gels, solutions, lotions, pads, and cleansers. Before applying benzoyl peroxide, patients should wash the affected area with mild, nonmedicated soap or skin cleanser and allow the skin to dry completely to reduce skin irritation. The skin should not be rubbed, but rather patted dry with a soft towel. Patients should apply enough medication to completely cover the affected areas and rub in gently while avoiding sensitive areas, such as those around the eyes, lips, in and around the nose, and areas of the neck.

When treatment with benzoyl peroxide is initiated, skin may feel irritated and acne may worsen. If acne does not improve within four to six weeks or if skin irritation is severe, patients should discontinue benzoyl peroxide products and consult a physician. 5 Pharmacists should instruct patients to not apply benzoyl peroxide to open wounds or windburned or sunburned skin and to not use other irritating products (e.g., peeling agents, hair removal products, agents containing large amounts of alcohol, abrasives, or drying agents) unless directed by a physician.5

Other OTC topical products used to treat acne contain resorcinol, salicylic acid, and/or sulfur. These products help break down plugs in lesions and decrease shedding of cells lining the hair follicles.1

Prescription medications: Moderate to severe acne may be treated with prescription oral and topical medications alone or in combination. Prescription topical medications include anti­ biotics, benzoyl peroxide, sodium sulfacetamide/sulfur combinations, azelaic acid, and vitamin A derivatives (retinoids). Retinoids work by unplugging existing comedones and decreasing the formation of new comedones and include such agents as tretinoin, adapalene (Differin/Galderma Laboratories), and tazarotene (Tazorac/Allergan).1

Prescription topical medications may cause minor side effects, such as stinging, burning, redness, peeling, scaling, or discoloration of the skin. Patients should notify their physician if side effects are severe or do not disappear. Prescription topical medications may not have an immediate effect, and it may take four to eight weeks before signs of improvement are visible. In addition, a patient's condition may worsen before it improves.

Oral and topical antibiotics control bacterial growth and reduce inflammation and are often used in combination. Commonly used oral antibiotics include tetracycline, minocycline, and doxycycline; oral antibiotics less commonly used are clindamycin, erythromycin, and sulfonamides. Side effects from oral antibiotics can include upset stomach, dizziness, changes in skin color, and increased tendency to sunburn. Since tetracyclines can affect tooth and bone formation in fetuses and young children, they are not used in pregnant women or in patients younger than 14 years.1

Severe cystic acne should be treated by a dermatologist, as it is often resistant to the treatments mentioned above. Cystic acne usually requires treatment with isotretinoin (Accutane/Roche), a retinoid that reduces the size of sebum-producing glands, to decrease oil production. Isotretinoin is taken orally once or twice daily for 15 to 20 weeks. Acne completely or almost completely disappears after 15 to 20 weeks of treatment with isotretinoin. If acne recurs, it can be treated with isotretinoin again or with other medications.

Since isotretinoin causes birth defects in developing fetuses, it is very important that women of childbearing age are not pregnant or do not become pregnant during treatment. Women must use two forms of birth control at the same time for a minimum of one month before treatment, during treatment, and for at least one month after treatment. In addition, pharmacists must register to prescribe and dispense iso­ tretinoin to ensure that it is not given during pregnancy. Both male and female patients who are prescribed isotretinoin must be registered to fill their prescriptions. Prescriptions must contain an authorization number, which is acquired by the physician when registering a patient; the number is then reported to the manufacturer by the pharmacist when the medication is dispensed.

Other possible side effects of isotretinoin include dry eyes, lips, nose, and skin, itching, nosebleeds, muscle aches, sensitivity to sunlight, poor night vision, increased blood triglycerides and cholesterol, and changes in liver function. Side effects usually resolve after treatment is completed.1

In some women, increased levels of androgens cause acne. This type of acne can be treated with oral contraceptives, low-dose corticosteroids, or spironolactone. Oral contraceptives and corticosteroids reduce androgen production by the ovaries and adrenal glands, respectively. Spironolactone has antiadrenergic properties. Spironolactone is a 17-lactone steroid that binds to androgen steroid receptors, thus blocking the effects of these androgens. Side effects of antiadrenergic medications include breast tenderness, irregular menstruation, headaches, and fatigue.1

Psychological Impact of Acne

Although acne is a minor medical condition that rarely has significant physical health consequences, the condition can have serious negative effects on psychiatric health, psychological well-being, and quality of life. Factors that contribute to the condition's psychological impact include its prevalence in adolescents, distribution of visible lesions on the face, back, chest, and upper arms, misconceptions regarding its causes, and social emphasis on appearance. Adolescence is a period of physical, emotional, and social development, and adolescents with acne may experience psychosocial complications. In addition, almost 30% of the American population believes that poor skin hygiene is a cause of acne.6 Such beliefs can cause patients to feel embarrassment, guilt, and shame. It is not surprising that when patients with acne were asked what bothers them the most about the condition, the most common response was appearance.7

Acne has been identified as a contributing factor of psychiatric disorders, including clinical depression, social phobias, and anxiety disorders.8,9 Acne can also negatively affect psychosocial functioning. Studies have identified significant impairment of self-esteem, self-image, well-being, and satisfaction with appearance in patients with acne, which inhibit social interaction.8-11 In addition, the condition has been shown to significantly affect quality of life.7 One study showed that 74% of patients with acne waited more than one year before seeking medical attention.6 This is an important concern because delaying treatment increases the likelihood of permanent scarring and allows time for patients to develop negative feelings about themselves. A study examining 111 patients before and after a variety of acne treatment modalities showed substantial improvements in quality of life and self- esteem with acne treatment.12

Such potentially serious psychosocial consequences must be considered when treating acne. Pharmacists can have a vital role in the effective treatment of acne, which can yield tremendous positive results in the self-esteem, self-image, and quality of life of patients. Patients should be encouraged to seek early treatment to minimize the chance of permanent physical scarring and negative psychological effects (table 2). Pharmacists should strive to be accessible, informed, and positive when counseling patients with acne.






Conclusion
Acne is a common dermatological problem that affects about 17 million Americans. The condition affects both men and women primarily during adolescence and can have significant negative psychological and psychosocial effects. Mild to moderate cases of acne can be minimized with early treatment and regular preventive skin care; in its most severe forms, acne can be effectively treated with prescription medications. Pharmacists can have a vital role in the effective treatment of acne, which can have a tremendous positive impact on a patient's self-esteem, self-image, and quality of life. To treat the entire person and not just the skin condition, the nondermatological effects of acne must be addressed.

REFERENCES

1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Questions and Answers About Acne. Available at: www.niams.nih.gov/hi/topics/acne/acne.htm. Accessed March 11, 2006.
2. Kamel MN. The Electronic Textbook of Dermatology. Anatomy of the Skin. Available at: www.telemedicine.org/stamford.htm. Accessed March 11, 2006.
3. American Academy of Dermatology. What is Acne? Available at: www.skincare physicians.com/acnenet/acne.html. Accessed March 11, 2006.
4. Acne.com. Pharmacological Triggers. Available at: www.acne.com/prevention/ medications.php. Accessed March 13, 2006.
5. MedlinePlus Health Information. Benzoyl Peroxide Topical. Available at: www.nlm.nih. gov/medlineplus/druginfo/uspdi/202086.html. Accessed March 13, 2006.
6. Tan JK, Vasey K, Fung KY. Beliefs and perceptions of patients with acne. J Am Acad Dermatol . 2001;44:439-445.
7. Lasek RJ, Chren MM. Acne vulgaris and the quality of life of adult dermatology patients. Arch Dermatol. 1998;134:454-458.
8. Kellett SC, Gawkrodger DJ. The psychological and emotional impact of acne and the effect of treatment with isotretinoin. Br J Dermatol. 1999;140:273-282.
9. Koo JY, Smith LL. Psychologic aspects of acne. Pediatr Dermatol. 1991;8:185-188.
10. Van der Meeren HL, van der Schaar WW, van den Hurk CM. The psychological impact of severe acne. Cutis. 1985;36:84-86.
11. Krowchuk DP, Stancin T, Keskinen R, et al. The psychosocial effects of acne on adolescents. Pediatr Dermatol. 1991;8:332-338.
12. Newton JN, Mallon E, Klassen A, et al. The effectiveness of acne treatment: an assessment by patients of the outcome of therapy. Br J Dermatol. 1997;137: 563-567.
13. Acne.org. Clear Skin Regimen. Available at: www.acne.org/regimen-instructions.html. Accessed March 13, 2006.

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