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Acne in the Post-Adolescent Female

DR SHOBHAN MANOHARAN

General and Laser Dermatologist

Brisbane Skin and Westside Dermatology

dd

DISCLOSURES

Allergan

Endymed

Inova

Leo

L’Oreal

Avita

Syneron Candela

Cynosure

Post Adolescent Female Acne

5

Acne Vulgaris: One of the Most Common Global Skin Diseases1

1. Tan & Bhate. Br J Derm 2015. 2. Smith et al. Am J Clin Nutr 2007. 3. Collier et al. J Am Acad Dermatol 2008

• Estimated to affect 9.4% of the global population, making it the eighth most prevalent disease worldwide1

• In Western populations2:• 79–95% of the adolescent

population• 40–54% of individuals older than 25• 12% of women and 3% of men by

middle age

• In adults, acne may have persisted since adolescence, be late-onset, or recurrent3

69%

43%

20%

12%

67%

51%

35%

26%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Pe

rce

nta

ge W

ith

Acn

e

Age (by Decade)

Men

Women

P < .0001

P < .0001

P = .0073

P = .5617

Teens 20s 30s 40s

N = 1013

Prevalence of Acne Reported By Age Group3

Adapted from Collier et al 2008

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Acne Is Common, But Not Trivial

1. Williams et al. Lancet. 2012; 2. Collier et al. JAAD. 2008; 3. Jacob et al. JAAD. 2001;4. Yin and McMichael. Am J Clin Dermatol. 2014; 5.Silverberg. Cutis. 2013; 6. Kelly. Cosmetic Dermatol. 2003; 7. Del Rosso and Kircik. J Drugs Dermatol. 2013; 8. Taylor et al. JAAD. 2002; 9. Davis and Callender. J ClinAesthet Dermatol. 2010; 10. Williams et al. Lancet. 2012; 11. Collier et al. J Am Acad Dermatol. 2008

• May lead to scarring

• Affects up to 20% of teenagers1

• Risk increases with longer acne duration2

• More common in patients with skin of colour4-6

• May cause dyschromia

• Persistent (post-inflammatory) erythema4,5,7

• Persistent (post-inflammatory) hyperpigmentation4,5,8

• May affect self-esteem10,11

• Even mild disease can have notable impact in some patients

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Pathophysiology

Types of lesions

“Blocked” follicle NoduleInflamed follicleMicrocomedone

Pustule

Gollnick H et al. J Am Acad Dermatol 2003; 49: S1- S37 and Galderma Data on File

Open

Comedone

“Blackhead

”

Closed

Comedone

“Whitehead”

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Classical View of Acne Pathophysiology1-3

1. Del Rosso and Kircik. J Drugs Dermatol. 2013; 2. Williams et al. Lancet. 2012; 3. Tanghetti. J Clin Aesthet Dermatol. 2013.

Normal –appearing skin • Increased androgens/ androgen sensitivity

• Increased sebum production

• Abnormal keratinocyte proliferation

• P. acnes proliferation

• Inflammation

Microcomedone

Non-inflammatory lesions(Open and closed comedones)

Resolution/scarring/dyschromia

Inflammatory lesions(Papules/pustules/nodules/cysts)

P. acnes = Propionibacterium acnes

Four primary causes of acne1

1. Thiboutot D et al. J Am Acad Dermatol 2009; 60 : S1–50.

Propionibacterium acnes (P acnes) follicular

colonisation

Sebum production by sebaceous gland

Alteration in keratinisation process

Inflammation and immune response

HORMONE MODULATED

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Normal-Appearing skin

Inflammation

Evolving View of Acne Pathophysiology:Inflammation Plays Key Role Throughout1,2

1. Del Rosso and Kircik. J Drugs Dermatol. 2013; 2. Tanghetti. J Clin Aesthet Dermatol. 2013.

Scar formation

Normal-appearing

skin

Dyschromia

Lesions Resolution

Subclinical inflammation

Papules, pustules,

or nodules

Micro-comedones

Open or closed

Comedones

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Key features of acne vulgaris:

A chronic inflammatory dermatosis

Closed comedones (whiteheads) and open comedones (blackheads)

• Mainly comedones, with an occasional small inflamed papule or pustule

MILD ACNE

• Comedones and more numerous papules and pustules, with lesions confined to the face

MODERATE ACNE

Moderate – Severe acne•Comedones, inflammatory lesions•Extensive involvementtrunk and limb

Moderate acne•Comedones•Inflammatory lesions-papules and pustules•Primarily face

MODERATE TO SEVERE ACNE

• Numerous comedones, papules and pustules, spreading to the upper trunk with an occasional cyst or nodule

• Numerous painful nodular lesions on the face, neck and upper trunk

SEVERE ACNE

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• Approach is multifactorial, targeting multiple pathogenic factors:• Sebum production

• Alteration of the keratinisation process

• P. acnes

• Inflammation

• Therapeutic goals:• Resolve existing lesions

• Prevent scarring

• Teaching to cope with psychological stress resulting from acne

Principles of acne treatmentInvestigations

• Microbial

• Endocrinological

Microbial

• In non-responders

• In sudden flares

• Rapid nodules

• Long term antibiotic usage – oral and topical

Endocrinologic

In post-pubertal females with

• Infrequent menses

• Hirsuitism

• Androgenetic alopecia

• Infertility

• PCOS

• Clitormegaly

• Truncal obesity

Tests

• Free and Total Testosterone

• DHEA-S

• Androstenedione

• LH, FSH

• Eostrogen, progesterone

• Sex hormone binding globulin

• prolactin

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First Line Therapy - GP

Oral antibiotics – doxy, mino (50bd); erythromycin (ees ii bd)

Topical retinoids (differin, epiduo)

Topical benzyl peroxide

Topical Dapsone (Aczone)

Topical abs (duac, eryacne)

OCP (yaz, yasmin, diane)

Spironolactone

Diet

Skin care regime

BASIC SKIN CARE

• Soap free cleanser

• Light moisturiser

• Light, non-comadogenic sunscreen

• Mineral makeup

Recommendations

• Low gi

• Dairy esp skim milk may exacerbate acne

Oral Antibiotics

• Tetracyclines – doxy, mino

• Erythromycin

• Bactrim

• Moderate to severe, with inflammation

• Limit to 3 months

• Use in combination with topical retinoid

• Rotation therapy

• Flare management

M.S.

20 year old swim teacher

Mild acne over a few years

Initially on Eryacne

Then put on doxycycline for 18 months

Sudden flare of skin

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Gram Negative Folliculitis

Long-term continuous tetracycline use

Swabs

Pseudomonas aeruginosa

Consider in non-responsive acne, or acne that flares suddenly in monomorphic form

My Mx

Pred 50

Ciprofloxacin 500mg bd

See back in 1wk with bloods for roac

Roac 20/d

Topical Antibiotics

• Erythromycin

• Clindamycin/Benzyl Peroxide

• Largely for spot treatment

• Not to be used as monotherapy – risk of bacterial resistance

• Combine with BP/retinoid

Topical Dapsone 7.5% (Aczone)

ACZONE® (dapsone) 7.5% w/w Topical gel: A Product for the Topical Treatment of Acne

• Once-daily dosing1

• Proven efficacy and tolerability1,2

• Studied in large pivotal trials

used for a topical acne drug2

• 4340 acne patients studied2

• 100% had moderate acne1,3

• Features a pump design1

1. ACZONE® Gel 7.5% w/w topical gel Australian Approved Product Information. 2. Thiboutot DM et al. J Clin Aesthet Dermatol2016; 9(10): 18-27. 3. Eichenfield MD et al. J Drugs in Dermatol 2016; 15(8) 962-69

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Study objective:

• To assess the safety and efficacy of dapsone 7.5% versus vehicle control administered topically once daily for 12 weeks in patients with acne vulgaris

End Points

• Co-primary:

– Global Acne Assessment Score (GAAS) success at week 12

– Mean reduction in inflammatory and noninflammatory lesion counts at week 12

• Secondary:

– Mean reduction in total lesions at week 12

– Percent reduction at week 12 for total, inflammatory, and noninflammatory lesion counts

Patients:

• ≥ 12 years of age with 20 to 50 inflammatory lesions and 30 to 100 noninflammatory lesions on the face at screening and baseline and with a score of 3 (moderate) on the GAAS

Study Design: Two Multicenter, Randomized,Double-blind, Vehicle-controlled, Parallel-group Studies1,2

1. ACZONE® 7.5% w/w Topical Gel Australian Approved Product Information; 2 Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27..

QD = once daily; R = 1:1 randomization.

Vehicle gel (n = 2178) QD; R

0 2 41 8 12Dapsone gel(n = 2162) QD; R

TotalPatientsN = 4340

Randomized1

Weeks

Pivotal Clinical Data:Efficacy and Safety

Pooled Analysis of Pivotal Trial Data

Clinical Success: Percentage of ACZONE® (dapsone) 7.5% w/w gel Patients With GAAS of 0 or 1 at Week 12

* as assessed by the investigator

1. ACZONE® 7.5% w/w Topical Gel Australian Approved Product Information; 2. . Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27.

.

Patients Achieved Success at Week 12 With a Score of 0 or 1 on the Global Acne Assessment

Score (GAAS) Scale1,2

30%

644 21%

4600%

20%

40%

60%

80%

100%

Total

AC

ZO

NE

®7.5

% P

erc

en

tag

e o

f Pa

tie

nts

Ac

hie

vin

g G

AA

S S

uc

ce

ss

ACZONE

Vehicle

P < .001

ACZONE® (dapsone) 7.5% w/w gel (n = 2162)

Vehicle (n = 2178) GAAS Scale2, *

0 = none

1 = minimal

2 = mild

3 = moderate

4 = severe

Effect of Once-Daily Application of ACZONE® (dapsone) 7.5% w/w Topical gel

1. Data on file, Allergan, 2016; Study Photos.

Actual, unretouched photos of an ACZONE® 7.5% w/w Topical Gel patient.1 Individual

results may vary.

Lesion Count Reductions

-70%

-60%

-50%

-40%

-30%

-20%

-10%

0%

0 1 2 3 4 5 6 7 8 9 10 11 12

Mea

n P

erce

nta

ge R

edu

ctio

nFr

om

Bas

elin

e

Week

Aczone Vehicle

(29.2) ACZONE® 7.5% w/w Topical gel

(29.7) Vehicle

-48.1%

(-13.9)

-54.6%

(-15.8)

P < .001

ACZONE® (dapsone) 7.5% w/w gel (n = 2162)

Vehicle (n = 2178)

Study design: Pooled analysis of 4,340 patients in 2 identical, 12-week, multicenter, randomized, double-blind, vehicle-controlled,parallel-group studies.

P<0.01

P<0.001

P<0.001

Adapted from Thiboutot 2016

Inflammatory Lesion Count Reduction At Week 121,*

1. Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27.

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-70%

-60%

-50%

-40%

-30%

-20%

-10%

0%

0 1 2 3 4 5 6 7 8 9 10 11 12

Me

an

Pe

rce

nta

ge

Re

du

ctio

n

Fro

m B

ase

line

Week

Aczone

Vehicle

(46.8) ACZONE® 7.5% w/w Topical gel

(47.6) Vehicle

-39.4%

(-18)

-45.1%

(-20.7)

P < .001

ACZONE® (dapsone) 7.5% w/w gel (n = 2162)

Vehicle (n = 2178)

Comedonal (Noninflammatory) Lesion Count Reduction at Week 121,*

1. ThiboutotDM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27.

.

P<0.001

Adapted from Thiboutot 2016

Study design: Pooled analysis of 4,340 patients in 2 identical, 12-week, multicenter, randomized, double-blind, vehicle-controlled,parallel-group studies.

Local Dermal Tolerability Assessments1

Pooled Tolerability:

• Erythema

• Scaling

• Dryness

• Stinging/Burning

1. ThiboutotDM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27.

.

Mean Severity Score

0 = none

1 = mild

2 = moderate

3 = severe

(n=2175)

(n=2161)

(PATIENT ASESSED)

Where Does Aczone Fit in My Practice?

• Monotherapy

• Combination therapy : eg Aczone mane, Retinoid nocte, OCP +/- Ab

• Antibiotic sparing agent

• Sensitive skin-types who cannot tolerate retinoid

• Rosacea

• Flare management

• Post-isotretion

Topical Retinoid

• Still cornerstone of first-line acne mx

• Adapalene, tretinoin, tazarotene

• Cat D/X -

• Comadonal acne

• Combination treatment

• Gradual increase in dose

• Appropriate emollients

Anti-Androgenic OCP

• Drospirenone

• Cyproterone acetate

• Well tolerated

• AFJA

• Combination therapy

• Acne antibiotics does not decrease contraception

• Monitor for 3 cycles prior to switching/ceasing

Spironolactone

• Aldosterone receptor antagonist

• Decrease T production and T binding to receptors in skin

• Well tolerated

• Diuresis, breast tenderness, menstrual irregularities, dizziness

• Hyperkalemia very rare

• 50-200mg

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Second Line Therapies – When to refer?

Unresponsive to first line agents

Truncal acne

Evidence of early scarring

Darker skin types

Second Line Therapies

Chemical peels

Laser and Light treatments

Comadonal Extractions

Isotretionoin

Oral Isotretinoin

Indicated in:

Nodular acne and severe variants

Not responding to other therapy

Scarring + postinflammatory hyperpigmentation

Darker skin types – lower threshold

Acne excoriae

• Pregnancy category X

• 1 month wash-out only

• Often combination on commencement to reduce flares – Abs, Pred, Aczone

• 6-12 mth Rx – longer in some, esp if Hx of PCOS

• Baseline and f/u ELFTs, Chol, TG

• Low dose routine often favoured – less SES, higher compliance, similar efficacy in most acne

PHYSICAL THERAPIES FOR ACNE

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ACNE SCAR TREATMENTS TCA CROSS

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Subscision

FRACTIONATED LASERS

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Benefits of Fractionation

• Less discomfort

• Less downtime, quicker heal

• Ability to penetrate deeper than with fully ablative settings.

• Ability to treat darker skin-types (IV-VI)

• Less complications (PIH and scarring)

• Ability to treat off the face (neck, chest, arms)

RADIOFREQUENCY

ABLATIVE LASER ReCell

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ReCell

• The ReCell Autologous Cell Harvesting Device creates an epithelial suspension which can be used to promote repigmentation and wound healing.

• FTSG or SSG processed into a non-cultured autologous suspension containing multiple skin cell phenotypes, including melanocytes.

• Immediate application to a wound bed, typically

prepared using dermabrasion or ablative laser.

• Removes need for wet lab.

FILLERS

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Newstead I Manly I North Lakes