Optimizing The Approach To Acne Therapy

Wilma F Bergfeld MD, FACPDepartments of Dermatology & Pathology

Cleveland Clinic FoundationCleveland, Ohio

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

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

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 -17 - 21 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 ChallengeReduce

• Microcomedones

• Micro-organisms

• Inflammation

• Androgen stimulation

• External irritants

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

Acne Targets

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

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

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

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

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

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:

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

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

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%

Hormonal Rx

• Usually in Females with severe acne resistant to common Rx.

• Hormones– Low dose BCP– Estrogens– Corticosteroids – Antiandrogens

• Retinoids-oral• Anti-inflammatory

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

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

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 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

Acne Rx Pitfalls

• Quick visit• Over Rx• Non-compatible Rx /

Lifestyles

• Irritation• Overwashing• Medical facials• Too many meds• Lack of education• Fear of therapies