# Presentation: 564258

## Optimizing The Approach To Acne Therapy

**Wilma F Bergfeld MD, FACP**
**Departments of Dermatology & Pathology**
**Cleveland Clinic Foundation**
**Cleveland, 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**

## 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 -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 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 -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**

## 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)364-92****:**

## 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**