Optimizing The Approach To Acne Therapy

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Optimizing The Approach To Acne Therapy

• Wilma F Bergfeld MD, FACP
• Departments of Dermatology Pathology
• Cleveland Clinic Foundation
• Cleveland, 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 199226931-935
• Cunliffe WJ. Br Med J 19791661109-1100

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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 gt 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 MgtF
• Teenage acne all types MgtF
• Adult acne papulopustular cysts FgtM

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Acne Epidemiology

• American teenagers -17 - 21 million
• American adults - 25 million
• F gt M
• United Kingdom adult women
• (20-58 years) gt 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 gtcytokines
• IL-1 induces Comedogenesis
• TLR-2 TLR4gtTNFa,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-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

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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 200021(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 198381(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 Gyn199789615-22

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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 patients 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