30-Aug-17 ACNE IN THE POST ADOLESCENT FEMALE DR J VON NIDA ROYAL STREET DERMATOLOGY SIR CHARLES GAIRDNER HOSPITAL DISCLAIMER ACNE

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1 DISCLAIMER ACNE IN THE POST ADOLESCENT FEMALE DR J VON NIDA ROYAL STREET DERMATOLOGY SIR CHARLES GAIRDNER HOSPITAL 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) 1

2 1 Halvorsen et al JID 2011:131: Aug-17 ACNE IS COMMON, BUT NOT TRIVIAL SCENARIO Acne affects >80% Teenagers. M=F. Adult Females (>25yrs) more prevalent (1/3 acne visits). May lead to scarring Affects up to 20% of teenagers 1 Risk increases with longer acne duration 2 More common in patients with skin of color 5-7 May cause dyschromia Persistent (postinflammatory) erythema 5,6,8 Persistent (postinflammatory) hyperpigmentation 5,6,9 May affect self-esteem 11,12 Even mild disease can have notable impact in some patients Jacob, Davis, 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 PSYCHOLOGICAL EFFECTS ACNE Increased likelihood of Self-consciousness Social Isolation Depression 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. Suicidal Ideation 1 A B Davis, 2010 Davis, 2010 C Plewig, Davis EC, and Callender VD. J Clin Aesthet Dermatol. 2010; 2. Plewig G and Kligman AM. Acne and Rosacea

3 PATHOPHYSIOLOGY CLASSICAL VIEW OF ACNE PATHOPHYSIOLOGY 1-3 Normal appearing skin Microcomedone Noninflammatory lesions (Open and closed comedones) Inflammatory lesions (Papules/pustules/nodules/cysts) Increased androgens/ androgen sensitivity Increased sebum production Abnormal keratinocyte proliferation P acnes proliferation Inflammation EVOLVING VIEW OF ACNE PATHOPHYSIOLOGY: INFLAMMATION PLAYS KEY ROLE THROUGHOUT 1,2 Normal-Appearing skin Subclinical inflammation Normalappearing skin Microcomedones Lesions Open or closed Comedones Papules, pustules, or nodules Resolution Scar formation Dyschromia Resolution/scarring/dyschromia Inflammation 1. Del Rosso and Kircik. J Drugs Dermatol. 2013; 2. Williams et al. Lancet. 2012; 3. Tanghetti. J Clin Aesthet Dermatol Del Rosso and Kircik. J Drugs Dermatol. 2013; 2. Tanghetti. J Clin Aesthet Dermatol

4 REVIEW OF EVIDENCE FOR KEY ROLE OF INFLAMMATION IN ACNE SOME KEY INFLAMMATORY MARKERS AND THEIR POTENTIAL ROLES IN ACNE Subclinical inflammation precedes microcomedone formation and persists through the scarring phase 1-5 Inflammatory lesions may arise directly from normalappearing skin 3,6 Inflammatory factors found around clinically normal pilosebaceous follicles in uninvolved skin of acne patients 5 Genes involved in inflammatory processes are upregulated in inflammatory acne lesions relative to normal skin without acne in the same patient 7 Normal-Appearing Skin Lesions Resolution 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 Interleukin-8 (IL-8) 1,2 Upregulated in inflammatory papules Neutrophil and lymphocyte chemoattractant Matrix metalloproteinases (MMPs) 1,2 Upregulated in inflammatory lesions Matrix metalloproteinases (MMPs) 1-3 Involved in extracellular matrix remodeling and may influence scar formation Recent evidence challenges the current nomenclature of noninflammatory vs inflammatory acne lesions 1,2 P acnes may interact with all of these markers 2 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 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 THE ROLE OF P ACNES: PRIMARY OR SECONDARY? ROLE OF THE SEBACEOUS GLAND Evidence for Classical View Close to 100% of adults have P acnes on their skin 1 P acnes density greatly increases at puberty (typical time of acne onset) 1 P acnes can have both comedogenic and proinflammatory effects 1 Evidence for Evolving View Less than half of adults have acne 3 P acnes density is not correlated with severity of inflammation in acne 2 Both comedones and inflammatory acne lesions may be sterile 2 Emerging evidence suggests that sebum lipid composition may be more important than sebum quantity in acne pathogenesis 1,2 Increased sebum alone does not induce acne 3 Changes in sebum lipid composition may contribute to an inflammatory cascade 3 Inflammatory mediators are both present and capable of promoting comedogenesis in the pilosebaceous unit 3 1. Shaheen and Gonzalez. Br J Dermatology. 2011; 2.Tanghetti. J Clin Aesthet Dermatol. 2013; 3. Collier et al. J Am Acad Dermatol Zouboulis et al. J Eur Acad Dermatol Venereol [Epub ahead of print]; 2. Youn et al. Br J Dermatol. 2005; 3. Tanghetti. J Clin Aesthet Dermatol ROLE OF ANDROGENS HYPERANDROGENISM Androgens induce sebum production and follicular hyperkeratinization in acne patients 1,2 Regulate sebaceous gland activity through androgen receptors in keratinocytes and sebocytes 3 Increased/altered sebum production due to androgens or increased androgen receptor sensitivity is believed to play a pivotal role in acne lesion formation 1,2 Seborrhoea Hirsuitism Androgenic Alopecia Cushingoid Features Increased Libido Increased levels of androgens are associated with increased acne Deepening of Voice Acanthosis Nigricans For example: puberty, 3 menses, 1 polycystic ovary syndrome 1 Cliteromegally 1. Williams et al. Lancet. 2012; 2. Bellew et al. J Drugs Dermatol. 2011; 3. Stein Gold. J Drugs Dermatol

5 Percentage of Patients Seeking Treatment 30-Aug-17 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 CLINICAL FEATURES Persistent Group Adolescence Adulthood % New Onset Group % Recurrent Group Adolescence Clears Returns in Adulthood.?% Mixture of comedonal, inflammatory and early cystic acne lesions affecting the lower Face and Jawlines. Pre-Menstrual Flare. Persisting Lesions. Treatment Resistant. MAJORITY OF THOSE SEEKING MEDICAL CARE FOR ACNE ARE ADULT FEMALES Most Seeking Care Are Over Age Women Seeking Care Outnumber Men by 2 to Females 65% Males 35% to 12 to 15 to 18 to 25 to 36 to Age Range (Years) Analysis of claims data for 9.6 million patients in over 80 US public and private healthcare plans in Yentzer et al. Cutis

6 EXAMPLES OF IMPACT OF ACNE ON BEHAVIOR From an online survey of 409 adult women (ages 25-45) with acne 1 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% *Most common changes were drinking more water (74%) and eating healthy foods (55%). 1. BuzzBack Market Research. Woman s Acne Exploratory TREATMENT OPTIONS I DON T WANT (INSERT DRUG NAME HERE). BUT FIX MY ACNE 6

7 PATIENT EDUCATION AND SUPPORT ADDRESS MYTHS ABOUT DIET The role of diet in acne occurrence/severity remains unclear 1,2 Emphasize that acne is a chronic disease requiring long-term management 1 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 information 1 Be aware of the potential impact of acne on the patient and refer to other specialties as appropriate 1 May Prevent Acne There is some evidence that a lowglycemic diet (eg, tubers, fruit, fish) may prevent acne 3 May Promote Acne Limited evidence for skim milk only 4 Weak evidence for chocolate: seems to have an effect only if large quantities of the pure form are consumed 5 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; 1. Williams et al. Lancet. 2012; 2. Data on file, Allergan, Inc.; 3. BuzzBack Market Research. Women s Acne Exploratory Block et al. J Am Acad Dermatol EXAMPLES OF APPROVED TREATMENTS FOR ACNE 1-4 TOPICAL Sulfone 1 Retinoids 2 Antibiotics 2 Azelaic acid 3 Salicylates 4 Benzoyl peroxide 2 ORAL Antibiotics 2 Isotretinoin 2 Contraceptives 2 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):

8 SYSTEMIC ANTIBIOTICS COMBINED ORAL CONTRACEPTIVE AGENTS Minomycin mg daily Doxycycline 100mg daily Alprim 300mg daily Roxithromycin 150mg daily 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 1 Archer JS et al JAAD 2002 June;46(6): SPIRONOLACTONE CYPROTERONE ACETATE Synthetic Steroid and weak Diuretic Improves Seborrhoea + Hypertrichosis mg daily Combine with an OCP. Prevent menstrual irregularities and menorrhagia Prevent pregnancy Flare on cessation of Rx 50mg daily for 5 th - 15 th day of cycle Combine with OCP Break through bleeding, dysmenorrhoea, mood changes, feminisation of male foetus PREGNANCY, BREASTFEEDING AND ACNE ACNE TREATMENT DURING PREGNANCY Hormonal acne generally flares durng 1 st trimester. Often improves as pregnancy continues. Breastfeeding usually slows the return of acne. Usually the acne is less severe over subsequent pregnancies. Benzyl Peroxide Erythromycin (Topical + Systemic) Clindamycin (Topical + Systemic) Azelaic Acid Combinations of the above 8

9 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: WHAT IS THE EFFICACY OF LIGHT THERAPY FOR ACNE? LIGHT THERAPY VS. ANTIBIOTICS 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 Natural No side effects Time consuming 15min per area Cost ~$150 per treatment Antibiotics Effective Cheap $30 per month Side-effects Un-natural 9

10 LIGHT THERAPY FOR ACNE SUMMARY Acne vulgaris affects nearly all adolescents and often persists into adulthood, especially in women 1,2 Approximately equivalent to antibiotics May work faster Less side effects Probably no long term remission Persistent acne can lead to undesirable sequelae 2,5,6 The pathophysiology of acne is not completely understood, but a growing body of evidence suggests that inflammation plays an important role throughout acne lesion formation 7,8 New insights into the pathogenesis of acne should be taken into account when considering treatment options 7,8 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