Severe Acne: An Update on Traditional Approaches

If one describes acne as a minor medical condition with insignificant consequences, affected teenagers will execute the adolescent eye roll. A scourge for 85% of young people - but a problem for all age groups and ethnicities - acne vulgaris affects 17 million Americans. Acne's visible lesions complicate rapid adolescent physical, emotional, and social development and may cause embarrassment, guilt, and shame at any age.^{1 A few cases persist past age 30.}2 Severe acne may contribute to clinical depression, social phobias or inhibition, and anxiety disorders.^{3-6 Successful treatment improves quality of life and self-esteem.}7Pathogenesis

Acne occurs when oil, dead cells, and bacteria clog pores and create noninflammatory follicular papules, especially on skin with dense sebaceous follicle concentration (the face, upper chest, and back). Severe forms are complicated by inflammatory papules, pustules, and nodules. Early intervention and preventive skin care can ameliorate mild-to-moderate cases.2,3All acne lesions begin as microcomedos in the pilosebaceous unit, which includes sebaceous glands and sebum, the hair follicle, the keratinocyte-lined follicle opening (pore), and a single hair. Normally, oily sebum is secreted via the pore.2 Should the unit malfunction, impeding sebum flow, bacteria that normally live on the skin's surface, Propionibacterium acnes, can flourish and attract white blood cells. Swelling, redness, heat, and pain lead to assorted lesions (Table 1).2,8Four primary factors contribute to acne lesion development: (1) abnormal keratinocyte desquamation, (2) increased sebum production, (3) P acnes proliferation, and (4) inflammation.Predisposing Factors

Familial history increases the likelihood of acne. Hormone fluctuations - especially elevated androgens beginning as early as 7 years of age^{9,10 and during puberty in either gender - enlarge sebaceous glands and increase sebum production. In girls and women, natural (premenstrual or pregnancy-related) or artificial (oral contraceptives) hormonal changes can affect acne.}11Many anticonvulsants, cortico steroids, and immunosuppressants can cause or worsen acne. Pressure points from athletic equipment or clothing, environmental or cosmetic grease, pollution, high humidity, and stress can aggravate acne. Scrubbing, squeezing, or picking lesions forces surface bacteria into pilosebaceous units and contributes to comedo formation.^{2 Chocolate, poor hygiene, and greasy foods do not affect acne.}2,12Treatment

Topical OTC benzoyl peroxide (BPO), a bactericidal that may reduce sebum production, has been the cornerstone of prevention. Other OTC topical products containing resorcinol, salicylic acid, and/or sulfur often are helpful.13Moderate-to-severe acne usually requires prescription-strength intervention. The recently released guidelines of the Global Alliance to Improve Outcomes in Acne (Table 2^{14,15) have updated traditional approaches. They recommend retinoids - tretinoin, adapalene, tazarotene (reserved in the past for patients with predominantly comedonal acne) - initially and for maintenance. Retinoids target microcomedos and decrease new comedone formation.}2 Topical and oral antibiotics, BPO, sodium sulfacetamide/ sulfur combinations, and azelaic acid also are used.Prescription topical medications may cause stinging, burning, redness, peeling, scaling, or skin discoloration. Patients should notify their physician if side effects are severe or if they persist. Improvement may take 4 to 8 weeks. In addition, acne may worsen before it improves.13Adjunctive Agents

Adjunctive oral minocycline and doxycycline - and other antibiotics to a lesser extent - control P acnes growth and have intrinsic anti-inflammatory properties. Side effects can include gastrointestinal distress, dizziness, skin color changes, and photosensitivity. Pregnant women and patients younger than 14 years must avoid tetracyclines because they affect tooth and bone formation.2Often stubbornly resistant, severe cystic acne usually requires treatment with isotretinoin - an oral retinoid that reduces sebum-producing gland size and oil production - once or twice daily for 15 to 20 weeks. Frequently, acne completely or almost completely disappears. If it recurs, it can be re-treated with isotretinoin or other medications.16The FDA has required increasingly strenuous risk management programs to prevent fetal exposure to isotretinoin, a known teratogen.^{17,18 Mandatory since March 1, 2006, the iPLEDGE program is the most rigorous risk management program in history for a widely prescribed drug19 (US pharmacists dispense more than 1.4 million isotretinoin prescriptions annually, 20 about half of them to girls and women of reproductive potential}18,21). Women of childbearing age must use redundant birth control beginning 1 month before and until 1 month after treatment with isotretinoin.Once isotretinoin is started, patients should discontinue oral antibiotics and topicals unless the physician directs otherwise. Patients often report very dry eyes, lips, nose, and skin. Itching, nosebleeds, muscle aches, photosensitivity, poor night vision, increased blood triglycerides and cholesterol, potentially increased suicide risk, and changes in liver function also are possible. Side effects usually resolve after treatment cessation.2,16,22In women who have a sudden onset of severe acne, who are unresponsive to conventional first-line therapy, or who have persistent inflammatory papules and nodules involving primarily the lower face and neck, oral contraceptives can improve acne by reducing androgen production. Spironolactone - a 17-lactone steroid that blocks the androgen effect - can help, too. Side effects of antiadrenergic medications include breast tenderness, irregular menstruation, headaches, and fatigue.2

End Note

Alternative treatments with fewer side effects are needed for severe acne vulgaris. Preliminary experience suggests that photodynamic therapy may have potential.

References

• Lasek RJ, Chren MM. Acne vulgaris and the quality of life of adult dermatology patients. Arch Dermatol. 1998;134:454-458.
• 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.
• 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.
• Koo JY, Smith LL. Psychologic aspects of acne. Pediatr Dermatol. 1991;8:185-188.
• Van der Meeren HL, van der Schaar WW, van den Hurk CM. The psychological impact of severe acne. Cutis. 1985;36:84-86.
• Krowchuk DP, Stancin T, Keskinen R, Walker R, Bass J, Anglin TM. The psychosocial effects of acne on adolescents. Pediatr Dermatol. 1991;8:332-338.
• Newton JN, Mallon E, Klassen A, Ryan TJ, Finlay AY. The effectiveness of acne treatment: an assessment by patients of the outcome of therapy. Br J Dermatol. 1997;137:563-567.
• American Academy of Dermatology. What Is Acne? Available at: www.skincarephysicians.com/acnenet/acne.html. Accessed March 11, 2006.
• Pochi PE, Strauss JS, Downing DT. Age-related changes in sebaceous gland activity. J Invest Dermatol. 1979;73:108-111.
• Pochi PE, Strauss JS. Endocrinologic control of the development and activity of the human sebaceous gland. J Invest Dermatol. 1974;62:191-201.
• Acne.com. Pharmacological Triggers. Available at: www.acne.com/prevention/medications.php. Accessed March 13, 2006.
• Tan JK, Vasey K, Fung KY. Beliefs and perceptions of patients with acne. J Am Acad Dermatol. 2001;44:439-445.
• MedlinePlus Health Information. Benzoyl Peroxide. Available at: www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601026.html. Accessed March 13, 2006.
• Ochsendorf F. Systemic antibiotic therapy of acne vulgaris. J Dtsch Dermatol Ges. 2006;4:828-841.
• Zaenglein AL, Thiboutot DM. Expert committee recommendations for acne management. Pediatrics. 2006;118:1188-1199.
• Strauss JS, Rapini RP, Shalita AR, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol. 1984;10:490-496.
• Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med. 1985;313:837-841.
• Mitchell AA, Van Bennekom CM, Louik C. A pregnancy-prevention program in women of childbearing age receiving isotretinoin. N Engl J Med. 1995;333:101-106.
• Food and Drug Administration. iPLEDGE update. 2006. Available at: www.fda.gov/cder/drug/infopage/accutane/iPLEDGEupdate200603.htm. Accessed February 10, 2007.
• Stern RS. Medication and medical service utilization for acne 1995-1998. J Am Acad Dermatol. 2000;43:1042-1048.
• Lindstrom J. Isotretinoin: Background and Regulatory History. FDA Joint Drug Safety and Risk Management Advisory Committee and the Dermatologic and Ophthalmic Drugs Advisory Committee Meeting. February 26-27, 2004. Available at: www.fda.gov/ohrms/dockets/ac/04/slides/4017s1.htm. Accessed February 10, 2007.
• Wysowski DK, Pitts M, Beitz J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol. 2001;45:515-519.