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ACNE IN THE POST ADOLESCENT FEMALE

DR J VON NIDA

ROYAL STREET DERMATOLOGY

SIR CHARLES GAIRDNER HOSPITAL

DISCLAIMER

• No conflicts of interest

ACNE

• Multifactorial Disorder of the Pilosebaceous Unit

• Clinically characterized by comedones, papules, pustules, cysts and scarring

• Significant Psychologic and Economic Impact (US $2.5 Billion annually)

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SCENARIO

• Acne affects >80% Teenagers. M=F.

• Adult Females (>25yrs) more prevalent (1/3 acne visits).

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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. Krowchuk. Pediatr Rev. 2005; 5. Yin and McMichael. Am J Clin Dermatol. 2014; 6. Silverberg. Cutis. 2013; 7. Kelly. Cosmetic Dermatol. 2003; 8. Del Rosso and Kircik. J Drugs Dermatol. 2013; 9. Taylor et al. JAAD. 2002; 10. Davis and Callender. J Clin Aesthet Dermatol. 2010; 11. Williams et al. Lancet. 2012; 12. 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 color5-7

• May cause dyschromia

• Persistent (postinflammatory) erythema5,6,8

• Persistent (postinflammatory) hyperpigmentation5,6,9

• May affect self-esteem11,12

• Even mild disease can have notable impact in some patients

Jacob, 20013

Davis, 201010

PSYCHOLOGICAL EFFECTS

• Increased likelihood of

• Self-consciousness

• Social Isolation

• Depression

• Suicidal Ideation1

1 Halvorsen et al JID 2011:131:363-70

ACNE

• Self-limiting disease, seen primarily in adolescents, involving the sebaceous follicles.

• Pleomorphic : comedones, papules, pustules, nodules and pitted or hypertrophic scars.

• Face, back, chest and shoulders. On the trunk lesions are more prevalent in the midline.

A

Davis, 2010

B

Davis, 2010

Plewig, 1993

C

1. Davis EC, and Callender VD. J Clin Aesthet Dermatol. 2010; 2. Plewig G and Kligman AM. Acne and Rosacea. 1993.

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PATHOPHYSIOLOGY

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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

Noninflammatory lesions(Open and closed comedones)

Resolution/scarring/dyschromia

Inflammatory lesions(Papules/pustules/nodules/cysts)

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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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REVIEW OF EVIDENCE FOR KEY ROLE OF INFLAMMATION IN ACNE

1. Stein Gold. J Drugs Dermatol. 2013; 2. Tanghetti. J Clin Aesthet Dermatol. 2013; 3. Del Rosso and Kircik. J Drugs Dermatol. 2013; 4. Lee et al. J Eur Acad Dermatol Venereol. 2013; 5. Jeremy et al. J Invest Dermatol. 2003; 6. Do et al. J Am Acad Dermatol. 2008; 7. Trivedi et al. J Invest Dermatol. 2006.

• Subclinical inflammation precedes microcomedone formation and persists through the scarring phase1-5

• Inflammatory lesions may arise directly from normal-appearing skin3,6

• Inflammatory factors found around clinically normal pilosebaceous follicles in uninvolved skin of acne patients5

• Genes involved in inflammatory processes are upregulated in inflammatory acne lesions relative to normal skin without acne in the same patient7

• Recent evidence challenges the current nomenclature of “noninflammatory” vs “inflammatory” acne lesions 1,2

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Matrix metalloproteinases (MMPs)1-3

• Involved in extracellular matrix remodeling and may influence scar formation

Interleukin-8 (IL-8)1,2

• Upregulated in inflammatory papules

• Neutrophil and lymphocyte chemo-attractant

Matrix metalloproteinases (MMPs)1,2

• Upregulated in inflammatory lesions

Interleukin-1 (IL-1)1,2

• Upregulated during prelesional inflammation

• May trigger follicular hyperkeratinization

Toll-like receptors (TLRs)2

• Markers of innate immune response

• Overexpressed in superficial epidermis of acne patients

Normal-Appearing Skin Lesions Resolution

SOME KEY INFLAMMATORY MARKERS AND THEIR POTENTIAL ROLES IN ACNE

1. Del Rosso and Kircik. J Drugs Dermatol. 2013; 2. Beylot et al. J Eur Acad Dermatol Venereol. 2014; 3. Sato et al. Biol Pharm Bull. 2011.

P acnes may interact with all of these markers2

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THE ROLE OF P ACNES:PRIMARY OR SECONDARY?

1. Shaheen and Gonzalez. Br J Dermatology. 2011; 2.Tanghetti. J Clin Aesthet Dermatol. 2013; 3. Collier et al. J Am Acad Dermatol. 2008

Evidence for Classical View

Close to 100% of adults haveP acnes on their skin1

P acnes density greatly increases at puberty (typical time of acne onset)1

P acnes can have both comedogenic and proinflammatory effects1

Evidence for Evolving View

Less than half of adultshave acne3

P acnes density is not correlated with severity of inflammation in acne2

Both comedones and inflammatory acne lesions may be sterile2

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ROLE OF THE SEBACEOUS GLAND

• Emerging evidence suggests that sebum lipid composition may be more important than sebum quantity in acne pathogenesis1,2

• Increased sebum alone does not induce acne3

• Changes in sebum lipid composition may contribute to an inflammatory cascade3

• Inflammatory mediators are both present and capable of promoting comedogenesis in the pilosebaceous unit3

1. Zouboulis et al. J Eur Acad Dermatol Venereol. 2013. [Epub ahead of print]; 2. Youn et al. Br J Dermatol. 2005; 3. Tanghetti. J Clin Aesthet Dermatol. 2013.

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ROLE OF ANDROGENS

• Androgens induce sebum production and follicular hyperkeratinization in acne patients1,2

• Regulate sebaceous gland activity through androgen receptors in keratinocytes and sebocytes3

• Increased/altered sebum production due to androgens or increased androgen receptor sensitivity is believed to play a pivotal role in acne lesion formation1,2

• Increased levels of androgens are associated with increased acne

• For example: puberty,3 menses,1 polycystic ovary syndrome1

1. Williams et al. Lancet. 2012; 2. Bellew et al. J Drugs Dermatol. 2011; 3. Stein Gold. J Drugs Dermatol. 2013.

HYPERANDROGENISM

• Seborrhoea

• Hirsuitism

• Androgenic Alopecia

• Cushingoid Features

• Increased Libido

• Deepening of Voice

• Acanthosis Nigricans

• Cliteromegally

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IX FOR HYPERANDROGENISM

• Lutenising Hormone (LH)

• Follicular Stimulating Hormone (FSH)

• Total Testosterone

• Prolactin

• Dehydroepiandrosterone (DHEA)

• 17-OH Progesterone

• TSH

• ACTH Stimulation Test

ADULT FEMALE ACNE

• Persistent Group – Adolescence ➤ Adulthood.

• 75-80%

• New Onset Group.

• 20-40%

• Recurrent Group – Adolescence ➤ Clears ➤ Returns in Adulthood.

• ?%

CLINICAL FEATURES

• Mixture of comedonal, inflammatory and early cystic acne lesions affecting the lower Face and Jawlines.

• Pre-Menstrual Flare.

• Persisting Lesions.

• Treatment Resistant.

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Males 35%

Females 65%

1. Yentzer et al. Cutis. 2010.

MAJORITY OF THOSE SEEKING MEDICAL CARE FOR ACNE ARE ADULT FEMALES

Analysis of claims data for ≈9.6 million patients in over 80 US public and private healthcare plans in 20041

0 to11

12 to14

15 to17

18 to24

25 to35

36 to64

65 +0

5

10

15

20

25

30

Age Range (Years)

Pe

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nta

ge o

f P

atie

nts

Se

eki

ng

Tre

atm

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t

Most Seeking Care Are Over Age 181 Women Seeking Care Outnumber Men by 2 to 11

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EXAMPLES OF IMPACT OF ACNE ON BEHAVIOR

1. BuzzBack Market Research. Woman’s Acne Exploratory. 2011.

Which of the following things do you do to cope with your acne?

Percentage of Respondents

Use a concealer to mask my pimples or blemishes 64%

Use makeup tricks to cover up my acne 61%

Use specific ways of styling my hair to cover up my acne 44%

Grow long hair to cover acne on my face 32%

Try to relax 58%

Exercise 44%

Avoid exercise and sweating 18%

Dietary changes* 91%

From an online survey of 409 adult women (ages 25-45) with acne1

*Most common changes were drinking more water (74%) and eating healthy foods (55%).

TREATMENT OPTIONS

“ I DON’T WANT (INSERT DRUG NAME HERE)…. BUT FIX MY ACNE”

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PATIENT EDUCATION AND SUPPORT

• Emphasize that acne is a chronic disease requiring long-term management1

• Explain that there is no cure for acne

• Emphasize that acne is not the patient’s fault

• Dispel myths about diet/hygiene and provide evidence-based information1

• Be aware of the potential impact of acne on the patient and refer to other specialties as appropriate1

1. Williams et al. Lancet. 2012; 2. Data on file, Allergan, Inc.; 3. BuzzBack Market Research. Women’s Acne Exploratory. 2011. 38

ADDRESS MYTHS ABOUT DIET

• The role of diet in acne occurrence/severity remains unclear1,2

1. Williams et al. Lancet. 2012; 2. Stein Gold. J Drugs Dermatol. 2013; 3. Cordain et al. Arch Dermatol. 2002; 4. Di Landro et al. J Am Acad Dermatol. 2012; 5. Block et al. J Am Acad Dermatol. 2011.

May Prevent Acne May Promote Acne

• There is some evidence that a low-glycemic diet (eg, tubers, fruit, fish) may prevent acne3

• Limited evidence for skim milk only4

• Weak evidence for chocolate: seems tohave an effect only iflarge quantities of the pure form are consumed5

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EXAMPLES OF APPROVED TREATMENTS FOR ACNE1-4

TOPICALSulfone1

Retinoids2

Antibiotics2

Azelaic acid3

Salicylates4

Benzoyl peroxide2

ORALAntibiotics2

Isotretinoin2

Contraceptives2

1. Wozel and Blasum . Arch Dermatol Res. 2014; 2. Zouboulis and Piquero-Martin. Dermatology. 2003; 3. Graupe et al. Cutis. 1996; 4. Zander and Weisman . Clin Ther. 1992;14(2):247-53.

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SYSTEMIC ANTIBIOTICS

• Minomycin

• 50-100mg daily

• Doxycycline

• 100mg daily

• Alprim

• 300mg daily

• Roxithromycin

• 150mg daily

COMBINED ORAL CONTRACEPTIVE AGENTS

• OCPs containing – Cyproterone Acetate, Desogestrel, Diengestrel, Drospirenone, Gestodene or low dose (100mcg) Levonorgestrel.

• Progesterone only OCPs and Implantable Contraceptives tend to worsen acne.

• Slow onset (3/12) and maximal results in 4-6/12.

• Combine with Top Rx’s and o Ab’s.

• Consider contraindications (eg. FHx Breast Cancer, Thrombophilias)

• A number of studies have shown no link between the intermittent or long term use of o Ab’s and OCP efficacy.1

1Archer JS et al JAAD 2002 June;46(6):917-23.

SPIRONOLACTONE

• Synthetic Steroid and weak Diuretic

• Improves Seborrhoea + Hypertrichosis

• 50 – 100mg daily

• Combine with an OCP.

• Prevent menstrual irregularities and menorrhagia

• Prevent pregnancy

• Flare on cessation of Rx

CYPROTERONE ACETATE

• 50mg daily for 5th - 15th day of cycle

• Combine with OCP

• Break through bleeding, dysmenorrhoea, mood changes, feminisation of male foetus

PREGNANCY, BREASTFEEDING AND ACNE

• Hormonal acne generally flares durng 1st trimester.

• Often improves as pregnancy continues.

• Breastfeeding usually slows the return of acne.

• Usually the acne is less severe over subsequent pregnancies.

ACNE TREATMENT DURING PREGNANCY

• Benzyl Peroxide

• Erythromycin (Topical + Systemic)

• Clindamycin (Topical + Systemic)

• Azelaic Acid

• Combinations of the above

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ISOTRETINOIN

• Highly effective (Adolescent Acne 80% cure with one course)

• Side Effects ++

• Birth Defects

• Dry Skin, Lips, Nose, Eyes

• Muscle Aches

• Initial Flare

• ? Depression (Recent Meta-Analysis ➤ No Effect)1

• ? Long Term Low Dose

1 Huang Y, Cheng Y. JAAD 2017:76:1068-76

WHAT IS THE EFFICACY OF LIGHT THERAPY FOR ACNE?

• Kawada et al• 30pts mild to moderate• Blue source weekly• Reduction of 64% lesions over 5 weeks

• Multicentre trial• 35pts• Broad spectrum twice weekly• 80% showed ‘improvement’ for mild to moderate acne in inflammation• “Faster than antibiotics”

LIGHT THERAPY VS. ANTIBIOTICS

Light therapy

• ‘Natural’

• No side effects

• Time consuming

• 15min per area

• Cost

• ~$150 per treatment

Antibiotics

• Effective

• Cheap $30 per month

• Side-effects

• ‘Un-natural’

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LIGHT THERAPY FOR ACNE

• Approximately equivalent to antibiotics

• May work faster

• Less side effects

• Probably no long term remission

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SUMMARY

• Acne vulgaris affects nearly all adolescents and often persists into adulthood, especially in women1,2

• Persistent acne can lead to undesirable sequelae2,5,6

• The pathophysiology of acne is not completely understood, but a growing body of evidence suggests that inflammation plays an important role throughout acne lesion formation7,8

• New insights into the pathogenesis of acne should be taken into account when considering treatment options7,8

• Long Term Suppression of the condition rather than cure.

1. White. J Am Acad Dermatol. 1998; 2. Collier et al. J Am Acad Dermatol. 2008; 3. Davis et al. J Drugs Dermatol. 2012; 4. Davis and Callender. J Clin Aesthet Dermatol. 2010; 5. Davis and Callender. J Clin Aesthet Dermatol. 2010; 6. Williams et al. Lancet. 2012; 7. Del Rosso and Kircik. J Drugs Dermatol. 2013; 8. Tanghetti. J Clin Aesthet Dermatol. 2013.