1. Acne Vulgaris Mandy Jones, PharmD, PA-C, BCPS Spring 2014

2. Clinical Types Noninflammatory – Open & closed comedones, papules, few pustules Inflammatory – Erythematous papules, pustules, possible scarring Mild→ Moderate→ Severe

3. Post-inflammatory hyperpigmentation

4. Pharmacologic Treatment: Patient Considerations Clinical type of acne (comedonal, inflammatory, nodular, etc) Severity of acne Skin type (Dry, Oily) Presence of scarring or post-inflammatory hyperpigmentation Menstrual history and signs of hyperandrogenism in women History of prior successful and failed treatments Allergies Medication adherence patterns History of acne promoting medications Pyschological impact of acne on the patient Patient preference and cost concerns

5. General Self Care Measures and Non- Pharmacologic Treatment Covered in OTC and listed in notes

6. General Treatment Pearls 8 weeks for microcomedo to mature Mild-Moderate→ Topical Moderate-Severe→ Systemic Topical therapy: – Consider skin type and dosage form

7. TOPICAL THERAPY

8. Topical Retinoids (TRs) Benzoyl Peroxide (BPO) Azelaic acid 20% Cream Dapsone 5% Gel Salicylic acid Topical antibiotics

9. Topical Retinoids tretinoin (Atralin™; Avita®; Renova®; Retin-A® Micro; Retin-A®; Tretin-X™) adapalene (Differin® XP; Differin®) tazarotene (Avage™; Tazorac®) MOA: Vitamin A derivatives----directly targets genes implicated in acne pathogenesis – Decreases comedogenesis by: binding to Retinoic acid receptors (RARs) and Retinoid X Receptors inside keratinocytes→ activation of regulatory DNA sequencing called retinoid hormone response elements→ transcription of target genes responsible for keratinization→ normalization of follicular keratinization and decreases cohesiveness of keratinocytes – Decreases inflammation : Retinoid receptor complexes compete for AP-1 (a key transcription factor in inflammation) and down regulates expression of toll-like receptor (TLR-2), which is responsible for the inflammatory mechanism in acne

10. Topical Retinoids Some specifics……..

11. Fact or Fiction? It doesn’t matter which TR to recommend….they’re all the same

12. Eh---it depends on the parameter Efficacy: – ?? Tazarotene >> Tretinoin & Adapalene?? – Head-to-head trials do not definitely support one TR over another in terms of efficacy Safety: – In order of INCREASING skin irritation: Adapalene << Tretinoin << Tazarotene And other nuances: – Atralin®- made with soluble fish proteins – avoid in fish allergy – Tretinoin and tazarotene are deactivated by sunlight and oxidized by BPO (can’t use together at same time) – Adapalene is stable in sunlight & in presence of BPO …..Epiduo® is combo product of adapalene and BPO

13. TOPICAL THERAPY Topical Retinoids (TRs) Benzoyl Peroxide (BPO) Azelaic acid 20% Cream Dapsone 5% Gel Salicylic acid Topical antibiotics

14. Systemic Therapy For moderate to severe acne – Oral Abx Minocycline, doxycycline (1 st line) Erythromycin, clindamycin (2 nd line) Sulfamethoxazole-trimethoprin (rarely) – Isotretinoin

15. Oral Abx Some specifics……………..

16. Fact or Fiction? Using antibiotics for acne increases the risk of being infected with resistant bacteria.

17. Somewhat true….but not terrible Oral AND topical→ resistant P. acnes & CNS & colonization with Strep. pyogenes Increased risk of strep throat and impetigo….but treatment is no different Resistant p. acnes more difficult to treat

18. Oral Abx: Recommendations Limit use to 12-18 weeks Never use as monotherapy…..combine with BPO to prevent resistance, or with TR to decrease duration of Abx use Once lesions clear, d/c Abx and use TR +/- BPO for maintenance Rec. Doxy over Mino – Mino higher cost, no definitive studies indicating Mino superiority, Mino assoc. with more concerning ADRs – If no response with Doxy, can switch to Mino (pts may respond to one tetracycline but not the other)

19. But what about the Doxy shortage? If you only have one salt form on your shelves, suggest using what you have – Hyclate and monohydrate equally effective, but hyclate associated with more GI upset Use TR plus BPO or topical Abx instead If oral Abx is needed, suggest – Minocycline $$ or macrolide (erythro or clinda)

20. Isotretinoin Reserved for severe recalcitrant acne, nodulocystic acne, or significant physical or psychological scarring Only acne agent that works on all 4 mechanisms of acne pathogenesis Exact MOA not known, but it: – Shrinks sebaceous glands, decreases sebum secretion thus reducing p.acnes growth – Fosters keratinocyte differentiation and normalizes desquamation

21. Isotretinoin, iPLEDGE, and other specifics

22. Acne Vulgaris Other therapies Oral contraceptives Spironolactone Oral corticosteroids Special populations/situations Post-inflammatory hyperpigmentation Pregnancy Pediatrics and adolescents

23. Oral Contraceptives TYPO in notes Preference/Pearls----should say: – AVOID 2 nd generation progestins in patients with acne (i.e. levonorgestrel; norgestrel) – 2 nd generation progestions: High affinity for androgen receptor→ most androgenic 1 st, 3 rd, 4 th generation OK to use