1. Optimizing The Approach To Acne Therapy Wilma F Bergfeld MD, FACP Departments of Dermatology & Pathology Cleveland Clinic Foundation Cleveland, Ohio

3. 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

4. Acne Psychological & 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

5. 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

7. Acne Classification Type –Comedonal –Papulopustular –Cysts Severity –Mild –Moderate –Severe

15. 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

17. Acne Epidemiology American teenagers -17 - 21 million American adults - 25 million –F > M United Kingdom adult women – (20-58 years) > males of all ages

18. Acne Diagnostic Criteria Patient History Physical Examination Lesion Type Location Severity Gradation Therapeutic Options Adverse Reactions Therapy Follow up

19. Acne Challenge Reduce Microcomedones Micro-organisms Inflammation Androgen stimulation External irritants

20. Acne Rx 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

21. Acne Targets Comedones –Retinoids –Benzoyl peroxide –Isotretinoin –Sulfur –Salicylic acid – BHA –Azeliac acid –Alpha hydroxy acid - AHA

22. Acne Targets Inflammatory papules-pustules-nodules Anti-microbial Antibiotics – Minocycline - Zithromycin Retinoids Accutane – Vitamin A Retinoids - topical Anti-inflammatory Corticosteroids Anti-oxidants Anti-androgens –Estrogens –Spironolactone –Flutamide Insulin resistance - Metformin Vitamins & minerals –Zinc –Vitamin C, E

23. Tretinoin Effects Influences desquamation of abnormal epithelium Alters microclimate of microcomedones Resolves mature comedones Prevents new lesions Enhances penetration of other drugs

24. Retinoids Topical –Tretinoin Retin A Retin A Micro Renova –Adapalene Differin –Tazarotene Tarzorac

27. 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

28. Acne Antimicrobial 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

30. Acne Bacterial 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

31. 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 :

32. Plasma Androgens Female 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

33. Acne Study OrthoTri-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

34. CCF Androgen Excess Study 1000 Females- Registry (1989) Acne –DHEAS 47% –Testosterone Total 28% Free 23% –Androstenedione 7% Hirsutism –DHEAS 50% –Testosterone Total 27% Free 5% Androstenedione 20%

35. Hormonal Rx Usually in Females with severe acne resistant to common Rx. Hormones –Low dose BCP –Estrogens –Corticosteroids –Antiandrogens Retinoids-oral Anti-inflammatory

36. Acne Therapeutic 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

37. Acne Newer Combined Therapies Combined Rx –Combination Antibiotic-BPO Erythromycin Clindamycin Combination Antibiotic-BP-Zinc Combined Oral & Topical Rx Combined Retinoids –oral – topical with above O

38. 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

39. Patient Compliance Important 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

40. Acne Rx Pitfalls Quick visit Over Rx Non-compatible Rx / Lifestyles Irritation Overwashing Medical facials Too many meds Lack of education Fear of therapies