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  • 1. Optimizing The Approach To Acne Therapy Wilma F Bergfeld MD, FACP Departments of Dermatology & Pathology Cleveland Clinic Foundation Cleveland, Ohio
  • 2. 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
  • 3. 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
  • 4. 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
  • 5. Acne Classification • Type – Comedonal – Papulopustular – Cysts • Severity – Mild – Moderate – Severe
  • 6. 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
  • 7. Acne Epidemiology • American teenagers -17 - 21 million • American adults - 25 million – F > M • United Kingdom adult women – (20-58 years) > males of all ages
  • 8. Acne Diagnostic Criteria • Patient History • Physical Examination • Lesion Type • Location • Severity Gradation • Therapeutic Options • Adverse Reactions • Therapy • Follow up
  • 9. Acne Challenge Reduce • Microcomedones • Micro-organisms • Inflammation • Androgen stimulation • External irritants
  • 10. 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
  • 11. Acne Targets • Comedones – Retinoids – Benzoyl peroxide – Isotretinoin – Sulfur – Salicylic acid – BHA – Azeliac acid – Alpha hydroxy acid - AHA
  • 12. 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
  • 13. Tretinoin Effects • Influences desquamation of abnormal epithelium • Alters microclimate of microcomedones • Resolves mature comedones • Prevents new lesions • Enhances penetration of other drugs
  • 14. Retinoids • Topical – Tretinoin • Retin A • Retin A Micro • Renova – Adapalene • Differin – Tazarotene • Tarzorac
  • 15. 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
  • 16. 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
  • 17. 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
  • 18. 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:
  • 19. 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
  • 20. 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
  • 21. 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%
  • 22. Hormonal Rx • Usually in Females with severe acne resistant to common Rx. • Hormones – Low dose BCP – Estrogens – Corticosteroids – Antiandrogens • Retinoids-oral • Anti-inflammatory
  • 23. 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
  • 24. 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
  • 25. 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
  • 26. 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
  • 27. Acne Rx Pitfalls • Quick visit • Over Rx • Non-compatible Rx / Lifestyles • Irritation • Overwashing • Medical facials • Too many meds • Lack of education • Fear of therapies