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Optimizing The Approach To Acne Therapy
Wilma F Bergfeld MD, FACPDepartments of Dermatology & Pathology
Cleveland Clinic FoundationCleveland, Ohio
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Acne Prevalence
• 25 - 85% of 12-24 year olds
• 8 -10% of 25 - 34 year olds
• 3 - 8% of 35 – 44 year olds
Stern RS JAAD 1992;26:931-935
Cunliffe WJ. Br Med J 1979;166:1109-1100
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AcnePsychological & Economic Impact
Quality of Life is Threatened - especially – moderate to severe acne– Feelings of Insecurity & Inferiority– Reduced Self Esteem & Self Confidence & Body Image– Embarrassment & Social Withdrawal & Depression & Anger &
Frustration & Confusion– Limitations in Lifestyle– Higher rates of Unemployment– Adults suffer > Adolescents
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Dermatologist vs
Non-Dermatologist•Problem of misdiagnosis & inappropriate Rx
Non-dermatologist•Problem of increased cost by
Non-dermatologist•Increase patient preference to see Dermatologist•Increase employment of Dermatologist by HMO/MC•Increased access to Dermatologists
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Acne Classification
• Type– Comedonal– Papulopustular– Cysts
• Severity– Mild– Moderate– Severe
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Acne Variants
• Neonatal – 1-3 months comedones without scarring
• Infantile acne – 3-6 months papulopustules with scarring – M>F
• Teenage acne – all types – M>F
• Adult acne – papulopustular – cysts –F>M
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Acne Epidemiology
• American teenagers -17 - 21 million
• American adults - 25 million – F > M
• United Kingdom adult women– (20-58 years) > males of all ages
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Acne Diagnostic Criteria
• Patient History• Physical Examination• Lesion Type• Location• Severity Gradation• Therapeutic Options• Adverse Reactions• Therapy • Follow up
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Acne ChallengeReduce
• Microcomedones
• Micro-organisms
• Inflammation
• Androgen stimulation
• External irritants
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AcneRx Targets
• Genetic predisposition• Inflammatory reaction
– Release of neuropeptides >cytokines– IL-1 induces Comedogenesis– TLR-2 & TLR4>TNFa,IL-2,IL-12 (monocyte & macrophage)
• Infectious agents– P acnes – proinflammatory lipids
• Release TLR-2 &TLR-4
• Keratinizing defects– Sebaceous gland -– Hair follicle – exiting canal keratinized
• Microcomedones - inflammation
• Hormonal influence– Androgens– Corticotropin-releasing hormone
20 World Congress, Derm Fast Facts, July 1-5,2002
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Acne Targets
• Comedones– Retinoids– Benzoyl peroxide– Isotretinoin– Sulfur– Salicylic acid – BHA– Azeliac acid– Alpha hydroxy acid - AHA
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Acne TargetsInflammatory papules-pustules-nodules
• Anti-microbialAntibiotics – Minocycline - Zithromycin
• RetinoidsAccutane – Vitamin A
Retinoids - topical
• Anti-inflammatoryCorticosteroidsAnti-oxidants
• Anti-androgens– Estrogens– Spironolactone– Flutamide
• Insulin resistance - Metformin• Vitamins & minerals
– Zinc– Vitamin C, E
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Tretinoin Effects
• Influences desquamation of abnormal epithelium
• Alters microclimate of microcomedones• Resolves mature comedones• Prevents new lesions• Enhances penetration of other drugs
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Retinoids
• Topical– Tretinoin
• Retin A• Retin A Micro• Renova
– Adapalene• Differin
– Tazarotene• Tarzorac
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Azelaic Acid• Natural occurring dicarboxylic acid• Antikeratizing & Antibacterial &
Anti-inflammatory• Mild to moderate acne• Used with combined Rx
– Oral antibiotics– Topical retinoids– AHA
• Absence of systemic AE or resistance to P acnes
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AcneAntimicrobial Rx
• Benzoyl peroxide is a potent bactericidal agent -2.5-10%– Improves comedones & papulopustules– Reduces P acnes– Can induce irritation
• Topical antibiotics – Erythromycin & Clindamycin– Reduces P acnes– Decrease neutrophilic & monocyte activity
• Oral Antibiotics– Tetracyclines– Broad spectrum antibiotics
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AcneBacterial Resistance
• Microcomedone – lipid environment– P acnes– P granulosum
• Organisms produce proinflammatory substances
• Sensitive to wide range of Antibiotic but Increasing Resistance
• Need for New Combined Rx
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Androgen Activity• Hair follicle
– Anagen bulb – androgen receptors
• Sebaceous gland– Androgen receptors– 5 AR type 1– Influenced by: Gonadotrophins, Insulin-like growth
factors, insulin, glucocorticoids, estrogen. Thyroid hormone
Deplewski D Endocrinol Rev 2000;21(4)364-92:
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Plasma AndrogensFemale Acne Patients
• Acne patients #-75n, 23 +/- 6,5 y– Most common elevated androgen-
• Free Testosterone - 25%• Free 17 beta-hydroxysteroids - 23% • DHEAS – 19%• Total Testosterone – 12%
• Lucky Aw J Investig Dermatol 1983;81(1):70-4
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Acne StudyOrthoTri-Cyclen
• 250 females/acne patients (15-49 y )• Moderate acne• 6 mo Rx with OrthoTri-Cyclen or placebo• Results:
– 51 % vs 35% reduction –lesions– 46 % vs 34 % total reduction-lesions– 83 % vs 63% improved
• Reduced testosterone & increased SHBG• Obst & Gyn1997;89:615-22
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CCF Androgen Excess Study1000 Females- Registry (1989)
• Acne– DHEAS 47%– Testosterone
• Total 28%
• Free 23%
– Androstenedione 7%
• Hirsutism– DHEAS 50%– Testosterone
• Total 27%• Free 5%
• Androstenedione 20%
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Hormonal Rx
• Usually in Females with severe acne resistant to common Rx.
• Hormones– Low dose BCP– Estrogens– Corticosteroids – Antiandrogens
• Retinoids-oral• Anti-inflammatory
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AcneTherapeutic Targets
• Comedogenesis– Retinoids– Benzoyl peroxide– Isotretinoin– Sulfur– Azelaic acid
• Sebum production– Retinoids– Antiandrogens– Low-dose BCP
• P. acnes– Antibiotics– Retinoids– Benzoyl peroxide
• Inflammation– Oral antibiotics– Retinoids
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AcneNewer Combined Therapies
• Combined Rx– Combination Antibiotic-BPO
• Erythromycin• Clindamycin
• Combination Antibiotic-BP-Zinc• Combined Oral & Topical Rx• Combined Retinoids –oral – topical with above
O
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Acne Patient Education
• Education• Discuss patient Expectations• Time Frame - Expected Improvement• Establish Therapy • Discuss Therapy Expectations & Adverse
Events • Re-Evaluation of Therapy • Patient Compliance Needed
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Patient ComplianceImportant
• Active agreement – Proposed Rx– Patient responsibilities– Discuss cost – Prescription choices– Mesh Rx Choice with patients Skin Type & Life Style– Allot time for patient’s questions
• Remember patient ability to listen to only 3 messages
• Provide Educational pamphlets/handouts• Provide patient with Written Instructions
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Acne Rx Pitfalls
• Quick visit• Over Rx• Non-compatible Rx /
Lifestyles
• Irritation• Overwashing• Medical facials• Too many meds• Lack of education• Fear of therapies