1. Treatment of Acne-II

2. Important points to remember! Self-treatment of acne is effective in patients mature enough to understand that acne can be controlled but not cured; Treatment of noninflammatory acne: pharmacologic agents + nonpharmacologic measures; Self treatment is appropriate only for grade I acne (i.e. noninflammatory acne of mild to moderate severity), presenting with open or closed comedones

3. Classification of Acne Grade of Acne Qualitative Description Quantitative Description IComedonal acneComedones only, < 10 on face, none on trunk, no scars, noninflammatory lesions only IIPapular acne10-25 papules on face and trunk, mild scarring, inflammatory lesions < 5 mm in diameter IIIPustular acneMore than 25 pustules, moderate scarring, size similar to papules but with visible purulent core IVSevere persistent pustulocyctis acne Nodules or cysts, extensive scarring, inflammatory lesions > 5 mm in diameter -Recalcitrant severe cystic acne Extensive nodules/cysts

4. Exclusion for Self-Treatment Grades II-IV acne: papules, pustules, nodules, cysts and/or scarring Severe, recalcitrant acne (extensive nodules/cysts) Exacerbating factors (e.g. comedogenic drugs) Possible rosacea (If acne lesions persist beyond mid-20s or develop in the mid-20s or later, the symptoms may signal rosacea rather than acne vulgaris)

5. Comedonal acne - topical treatment appropriate: Pustular - an oral antibiotic would be best:

6. A) Before treatment: Severe acne treated with Isotretinoin: B) After 5 months

7. Prescription Medication for acne: Retinoic acid & Derivatives Isotretinoin Azelaic Acid Antibiotics (topical or systemic) Hormonal therapy

8. Retinoic Acid & Derivatives Retinoic acid (tretinoin) is the acid form of vitamin A 13-cis-retinoic acid (isotretinoin) is analog of retinoic acid effective when given orally Retinoic acid insoluble in water; susceptible to oxidation and ester formation particularly when exposed to light; Topically applied retinoic acid remains chiefly in the epidermis (< 10% absorbed)

9. Retinoic Acid & Derivatives The small quantities absorbed following a topical application are metabolized by the liver and excreted in bile and urine; Retinoic acid has several effects on epithelial tissues (lysosomes, PG-E2, cAMP, cGMP and RNA polymerase) Action in acne: (1) decreased cohesion between epidermal cells (2) increased epidermal cell turnover. This results in expulsion of open comedones and transformation of closed comedones into open ones

10. Retinoic Acid & Derivatives Retinoic acid is applied initially in a concentration sufficient to induce slight erythema with mild peeling If too much irritaion is produced, decrease concentration or frequency of application; During the first 4-6 weeks of therapy, comedones not previously evident may appear However, with continued therapy, the lesions will clear, and in 8-12 weeks optimal clinical improvement should occur (Retin-A Micro): timed release formulation with tretinoin containing microspheres. Less irritating

12. Retinoic Acid & Derivatives Prolonged use of tretinoin promotes : (1) dermal collagen synthesis (2) new blood vessel formation (3) thickening of the epidermis Which helps diminish fine lines and wrinkles Renova (0.05% cream): specially formulated for this purpose

13. Retinoic Acid & Derivatives The most common adverse effects (topical): 1.erythema, dryness: first few weeks of use, but resolve with continued therapy; 2.May increase tumerogenic potential of UV radiation (in animals). Thus, patients are advised to minimize or avoid sun exposure and use protective sunscreen 3.Allergic contact dermatitis: rare

14. Retin-A dryness and irritation

15. Adapalene (Differin) A derivative of naphathoic acid that resembles retinoic acid in structure and effects Applied 0.1% gel once daily Unlike tretinoin: 1. photochemically stable 2. less irritating Most effective: mild to moderate acne vulgaris

16. Treatment with Adpalene gel

17. Tazarotene (Tazorac) Acetylenic retinoid 0.1% gel Treatment of mild to moderately severe facial acne Should not be used by pregnant women (pregnancy risk factor=X) Contraceptive counseling in women of childbearing age.

18. Isotretinoin (Accutane) A synthetic retinoid currently restricted to the treatment of severe cystic acne that is recalcitrant to standard therapies; Well absorbed to circulation, extensively bound to plasma albumin, elimination half-life of 21 hrs (parent drug), 21-24 hrs (metabolite) MOA: inhibits sebaceous gland size and function  ….details

19. MOA- isotretenoin: Isotretinoin prevents the formation of new comedos and resultant inflammatory lesions by: 1. decreasing the size and secretions of the sebaceous glands, 2.normalizing follicular keratinization, and 3.exerting anti-inflammatory effects. Sebum production is reduced by at least 90% through competitive inhibition of retinol dehydrogenase-4, the enzyme that mediates the skin's production of dihydrotestosterone and androstenedione.

20. Isotretinoin (Accutane) Dose: 0.5-2 mg/kg/day, given orally in two divided doses daily for 4-5 months; If severe cystic acne persists following this initial treatment, a second course of therapy may be initiated after 2 months; The skin would be sensitive during treatment. Patient is at high risk for abnormal healing and development of excessive granulation following procedures (e.g. piercing, tatoos, epilation)

21. Isotretinoin is available in 10-, 20-, and 40-mg soft gelatin capsules for oral administration. Isotretinoin capsules should always be taken with food to maximize absorption

22. Isotretinoin (Accutane) Adverse Effects Common adverse effects (resemble hypervitaminosis A): Dryness and itching of skin and mucous membranes Less common: Headache, corneal opacities, pseudotumpr cerebri inflammatory bowel disease, anorexia, alopecia, muscle and joint pains These effects are all reversible on discontinuation of therapy.

23. Isotretinoin (Accutane) Adverse Effects Skeletal hyperostosis has been observed in patients receiving isotretinoin Premature closure of epiphyses noted in children treated with this medication Lipid abnormalities (triglycerides, HDL) are frequent Depression, psychosis, aggressiveness or violent behavior & rarely suicidal thoughts (discontinuation MAY NOT be sufficient) Teratogenecity

24. the skull, ears, and eyes and include facial dysmorphia and cleft palate. Internal abnormalities affecting the thymus gland, central nervous system, cardiovascular system, and parathyroid gland (hormone deficiency) are recognized. In some cases, these abnormalities have resulted in fetal death. Nursing mothers should not receive isotretinoin.

25. Facial dysmorphism

26. Cleft palate

27. Isotretinoin (Accutane) Teratogenecity 1.Women of childbearing age must use an effective form of contraception for at least 1 month before; throughout isotretinoin therapy, and for one or more menstrual cycles following discontinuance of therapy 2.A serum pregnancy test must be obtained within 2 weeks before starting therapy 3.Therapy should be initiated only on the second or third day after the next normal menstrual period

28. Isotretinoin (Accutane) Monitoring parameters: 1.CBC with differential & platelet count, baseline sed. rate, glucose, 2.Pregnancy tests 3.Lipids: prior to treatment & at weekly or biweekly intervals until response to treatment is established 4.Liver function tests: prior to treatment & at weekly or biweekly intervals until response to treatment is established 5.Creatine Phosphokinase 6.Blood Glucose

29. Azelaic Acid (Azelex) Straight chain saturated dicarboxylic acid; effective in the treatment of acne vulgaris; Its mechanism of action not fully determined. However, studies shown: 1.Antimicrobial activity against P acnes 2.In vitro inhibition of the conversion of testosterone to dihydrotestosterone Initial therapy: once daily application of 20% cream to affected areas for 1 week. Then twice daily thereafter Mild irritation with redness and dryness of the skin during the first week of treatment Clinical improvement 6-8 weeks of continuous therapy

30. Topical Antibiotics Commonly prescribed: erythromycin and clindamycin alone or in combination with benzoyl peroxide MOA: (1) bactericidal activity against P acnes. (2) may also have anti-inflammatory effect Topical antibiotics are not comedolytic, Bacterial resistance may develop to any of these agents. The development of resistance is lessened if topical antibiotics are used in combination with benzoyl peroxide

31. Systemic Antibiotics Tetracycline and congeners (minocycline and doxycycline) Erythromycin, azithromycin Trimethoprim alone or in combination with sulfamethoxazole MOA: (1) P acnes; (2) Anti-inflammatory Minocycline is more effective than tetracycline and bacteria has less resistance to this agent

32. Systemic Antibiotics Bacterial resistance to these agents may be reduced by combining them with topical retinoids and/or topical benzoyl peroxide Most common side effects: phototoxicity from tetracycline group, especially doxycycline Vertigo-like dizziness>> minocycline Stevens-Johnson syndrome>> trimethoprim- sulfamethoxazole All oral antibiotics predispose to Candida infections, particularly vaginitis

33. Stevens Johnsons Syndrome

36. Hormonal Therapy MOA: estrogens are responsible for maintenance of the normal structure and function of the skin and blood vessels Acne may be exacerbated by agents containing androgen-like progestins (e.g. norethindrone, lynestrenol, norethynodrel), whereas agents containing large amounts of estrogen usually cause marked improvement in acne

37. ProgestinProgestational Activity (relative to 1 mg of norethindrone) Androgenic Activity (relative to 1 mg of norethindrone) norethindrone 1 mg1.0 norethrindrone acetate 1 mg1.21.6 ethynodiol diacetate 1 mg1.40.6 levonorgestrel 1 mg5.38.3 dl-norgestrel 1 mg2.64.2 norgestimate 1 mg1.31.9 norelgestromin 1 mg1.31.9 desogestrel 1 mg9.03.4 drospirenone 1 mg1.50.0

38. Ethinyl estradiol + Drospirenone

39. Hormonal Therapy FDA approved a triphasic, combination OCP: Ortho-Tri-Cyclen: Ethinyl estradiol (0.035 mg) + Norgestimate: Days 1-7 ………. 0.18 mg Days 8-14……….0.215 mg Days 15-21………0.25 mg

40. Hormonal Therapy A study showed that this OC reduced acne lesion counts by more than 50% in female subjects, compared with lesion reductions of about 26% in controls Acne improvement during treatment with Ortho- Tri Cyclen may take 3-4 months to become apparent; Main limitation of anti-androgen therapy for acne is that it cannot be used with male patients