Acne Vulgaris: Therapy Demystified

Stacey Northgrave, MD, MSc, FRCPC Dalhousie Spring Refresher: Therapeutics Saturday, March 9, 2019 Conflict of interest:

• I have received payment for giving talks from companies that manufacture some of the products that I will discuss such as Galderma and Valeant.

• I will use some trade names and discuss off label use of medications

• Receiving evaluations is critical to the accreditation process. Objectives:

1. To be familiar with treatment options for acne vulgaris 2. To have an approach to patients presenting with acne vulagris 3. To recognize mimickers of acne vulgaris Most helpful references:

• Management of acne: Canadian Clinical Practice guideline. CMAJ. 2016 – High strength: definitely use – Medium strength: Can be recommended; definitely use if higher strength recommendation is not available or appropriate – Low strength: May be considered, if higher strength recommendation is not available or appropriate – Negative strength: Not recommended – Open strength: Recommendations for or against cannot be made at this time • Guidelines for care for the management of acne vulgaris. JAAD. 2016 • European evidence-based (S3) guideline for the treatment of acne – update 2016. JEADV. Statistics:

• Number needed to treat: 4,836,932 in order to get 1 satisfied teenager Acne Vulgaris:

• Extremely common • Affects 85% of adolescents and young adults, 12 to 24 years old • Often persistent with 26% of women and 12% of men reporting persistence into their 40’s

• There are other forms of acne such as neonatal acne, medication induced acne etc which will NOT be discussed here Etiology:

1. Follicular plugging 2. Sebum production 3. Hormonal influences 4. Proprionibacterium Cutibacterium acnes Case:

• 16 year old female • 2 year history of eruption on face • Tried numerous OTC products (Oxy pads, Clearsil, Proactiv) but little results Diagnosis?

• Acne vulgaris • Severity? – Mild-moderate paapulopustular acne • Any other questions you would have for the patient? – Involvement of anywhere other than the face? – Any triggers? – Is she sexually active? – Skin oily or dry? – Skin easily irritated? Topical Treatments:

• Retinoids: • MOA: comedolytic (helps unblock the follicle) as wells as being anti-inflammatory • Agents: – (Differin): mildest • Available in 0.1% cream and gel • 0.3% (Differin XP) – Tretinoin: • Stieva-A Cream: 0.01%§, 0.025%§ and 0.05% § • Retin-A 0.025% Gel § and 0.05% Cream § • Retin-A Micro Gel: 0.04% and 0.1% § Covered under family pharmcare Topical Treatments:

• Retinoids (con’t): – Tazarotene (Tazorac): Strongest • Available in 0.05% § or 0.1% § • Cream § or gel § • Hints: – Photosensitizing: Use sunscreen – Irritating: Wait 20-30 minutes after washing; moisturize – Contra-indicated in pregnancy Topical Treatments:

• : – MOA: bactericidal and mild comedolytic – OTC: <=5%; Rx >5% – Washes: • Benzac 10 Wash: 10% BP Rx • Benzac 5 Wash: 5% BP OTC Topical Preparations:

• Hints: – Allergen – Bleaching agent – Irritant – Helps prevent resistance • Strength of recommendation: – Medium strength for comedonal acne Topical Treatments: • : • Hints: – Not recommended as monotherapy in order to reduce the risk of developing bacterial resistance – Not recommended to use in conjunction with another (orally or topically) in order to reduce the risk of developing bacterial resistance

– Dapsone: Aczone Gel – Azealic acid: Finacea Gel – Clindamycin: Dalacin T Combination Topical Treatments:

• Retinoids and antibiotics: – Stievamycin (erythromycin and tretinoin): Gone – Biacna: Tretinoin 0.025% and clindamycin 1.2% • Benzoyl peroxide and antibiotics: – Benzamycin: Benzoyl peroxide 5% + erythromycin 3% – BenzaClin: Benzoyl peroxide 5% + clindamycin 1% – Clindoxyl: Benzoyl peroxide 5% + clindamycin 1% – Taro BP/Clindamycin: Benzoyl peroxide 5% + clindamycin 1% Combination Topical Treatments:

• Benzoyl Peroxide and adapalene: – TactuPump: • Benzoyl peroxide 2.5% and adapalene 0.1% – TactuPump Forte: • Benzoyl peroxide 2.5% and adapalene 0.3% Topical treatments:

• Comedonal acne: – Benzoyl peroxide: medium strength of recommendation – Retinoids: medium strength of recommendation • Adapalene + tazarotene > tretinoin – Combination BP and adapalene: medium strength of recommendation – Combination of BP + clindamycin: medium strength of recommendation – Clindamycin + Tretinoin: low strength of recommendation • European guidelines also suggest azealic acid (Finacea): low strength Topical treatments:

• Localized mild to moderate pustular acne: – Benzoyl peroxide: high strength of recommendation – Retinoids: high strength of recommendation – Combination BP and adapalene: high strength of recommendation – Combination of BP + clindamycin: high strength of recommendation – Clindamycin + Tretinoin: low strength of recommendation Oral antibiotics:

• Indicated for more severe or widespread papulopustular acne vulgaris • Used in combination with topical medications: – Not used as monotherapy – Not used in combination with topical antibiotic • Strength of recommendation: Moderate • Avoid other antibiotic classes such as penicillins, macrolides and fluoroquinolones Oral Antibiotics:

• Tetracyclines are first line – Side effects include: • GI upset, headache (pseudotumour cerebri), vaginal candidiasis, photosensitivity, decreased absorption in the presence of food, staining of enamel in children • *AAD dosing guideline • **What I do • Tetracycline: – Children: 8 years of age; 25-50 mg/kg divided QID* – Adults: – 1 g in divided doses with decrease to 125 mg to 500 mg po daily* – 500 mg po BID** Oral antibiotics:

• Doxycycline: – Children: > 8 years of age; 1 mg/kg div po BID on the first day of treatment then 0.5 mg/kg po once daily or div BID* – Adults: • 100 mg po BID on the first day of treatment then 100 mg po daily* • 100 mg po BID** Oral antibiotics:

• Minocycline: – Children > 8 years of age • 4 mg/kg po div BID then to 2 mg/kg div BID* – Adults: • 50 mg po once daily to TID (100 mg po BID)* • 100 mg po BID** – Lightheadedness (weight dependent) – Minocin hyperpigmentation – Minocin hypersensitivity syndrome; Drug induced lupus and hepatitis (Not recommended in French 2017 guidelines)

Oral Antibiotics:

• Second line agents: – Erythromycin: 500 mg po BID • Increased rate of resistance of C. acnes • GI upset – Trimethoprim-sulfamethoxazole: 160 mg TMP/800 gm SMX – Trimethoprim: 300 mg po BID Oral Antibiotics:

• Concerns: – Bacterial resistance: • Limit exposure: Trial of 2-3 months • Avoid combination of antibiotics • Use in conjunction with benzoyl peroxide: – Bacteriocidal – Converted to benzoic acid and free O2 radicals that disrupt bacterial cell membranes Hormonal agents:

• Indicated for more severe papulopustular acne in women desiring contraception – Often used off label in adolescents who are not sexually active • Strength of the recommendation is moderate • Slow onset of action: 3-6 months • Can be used in combination with topicals and oral antibiotics Hormonal Agents:

• Combined oral contraceptive pills: – Estrogen: ethinyl estradiol • Increase SHBG production in the liver • Neg. feedback for LH/FSH and downstream androgen production – Progesterone: • Non-androgenic progestins: norgestimate and levonorgestrel • Progesterone given alone or in high doses can precipitate or aggravate pre-existing acne: – Medroxyprogesterone (Provera) 3-monthly depot inj. – Levonorgestrel implants (Norplant) – Mirena IUD Combined Oral Contraceptive Pills:

OCP Estrogen Progesterone Loestrin, LoLo Ethinyl estradiol Norethidrone1 Tricyclen Ethinyl estradiol Norgestimate2 Cyclen Tri-Cyclen LO Alesse, Aviane Ethinyl estradiol Levonorgestrel2 Tri-phasil, Tri-Quilar Min-Ovral

Marvelon 21 and 28 Ethinyl estradiol Desogestrel3

Yasmin Ethinyl estradiol Drospirenone

Diane 35, Cyestra 35 Ethinyl estradiol Cyproterone acetate Hormonal Agents:

• Androgen Receptor Blockers: – Diane 35: 35 mcg of ethinyl estradiol and 2 mg of cyproterone acetate – Yasmin: 30 mcg of ethinyl estradiol and 3 mg of drospirenone Combined oral contraceptives:

• Concerns: – Venous thrombosis and thromboembolism: • Avoid high risk patients (personal or family history of thromboembolism, smoking, >35 years of age, obesity) • Risk: Population: Risk/10,000 woman/years Non preg, non COC users 1-5 COC users 3-9 COC with drospirenone users 10 Pregnant women 5-20 Within 12 weeks post-partum 40-65 Hormonal Agents:

• Spironolactone: – Not included in Canadian guidelines but in American and European guidelines • 50-200 mg po daily • Off-label use • Minimal published data – Risks: • Diuresis (29%), menstrual irregularities (22%), breast tenderness (17%), breast enlargement, fatigue, and dizziness • Risk of hyperkalemia – Check potassium if on ACE inhibitor, ARB, NSAID, Digoxin Isotretinoin:

• Indications: – Severe nodulocytic acne – Scarring – Treatment resistant acne vulgaris • Strength of recommendation: High • Different formulations available: – Accutane, Clarus – Epuris Isotretinoin:

• Dose: – 0.5mg/kg/d x 1 month then 1 mg /kg/d for 4-5 months (or more) – Cumulative dose of 120-150 mg/kg Isotretinoin:

• Side effects: – TERATOGENICITY – Xerosis: Eyes, nose, lips (*contacts) – Photosensitivity – Increased lipid or elevation of liver enzymes – Headache, muscle aches, flare of acne, hair shedding – Risk of depression? – Risk of inflammatory bowel disease? Case:

• 16 year old female – Acne limited to her face with only the occassional lesion on her back – Menses are regular – Flare of acne premenstrually – Not sexually active – Skin only oily in T-zone – History of easily irritated skin

Case:

• Severity of acne? – Mild to moderate • Treatment? – Mild wash – Combination benzoyl peroxide and clindamycin preparation – If not responding to above, consider adding in Tricyclen or Alesse Cost? Mimickers of acne vulgaris:

• 32 year old female • Developed a “rash” on her face 6 weeks ago • Initially just on her chin • She used her husband’s “eczema cream” for his hands • Initially it helped but it has been getting Perioral Dermatitis progressively worse Mimickers of acne vulgaris:

• 28 year old male • Recurrent crops of papules and pustules on the nose and medial malar area • Tried over the counter acne products but significantly irritated skin Papulopustular rosacea Mimickers of acne vulgaris:

• 8 year old young man is brought to the office by his mother • She had problems with acne as a teenager and is worried since her son is starting so early • He has a history of hayfever and mild atopic dermatitis as an infant Keratosis pilaris Thank you!