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

Acne Prevalence % of year olds 8 -10% of year olds 3 - 8% of 35 – 44 year olds Stern RS JAAD 1992;26: Cunliffe WJ. Br Med J 1979;166:

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

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

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

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

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

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

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

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

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

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

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

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

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

Acne Antimicrobial Rx Benzoyl peroxide is a potent bactericidal agent % –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

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

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) :

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

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

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%

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

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

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

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

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

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