Acne & Psoriasis

1. Acne & Psoriasis ICARE Spring 2011 Michelle L.Rager, PharmD, BCPS

2. Acne Vulgaris

3. Epidemiology • Most common skin disorder in the US • Affects up to 50 million people • 80% of the population between the ages 11-30 • No gender, race or ethnicity prevalence • Age of onset varies • Usually begins at puberty • Adult acne can first occur after mid-20’s • Affects females more than males • Lesions generally distributed in lower facial area around the mouth, chin, and jaw line

4. Impact of Disease • More than $1.4 billion is spent on acne medications each year • Localization of acne vulgaris on the facial area significantly impacts self-esteem • Although acne is self-limiting, it can persist for years and cause disfigurement and scars • Associated with anxiety, depression, and higher-than-average unemployment rates

5. Etiology - 4 primary Factors • Increased sebum production • Androgen stimulation is enhanced at puberty • Androgenic activity drives sebum production • Not necessarily responsible for acne, but underlying factor • Sloughing of keratinocytes • Primary factor in development • Sloughing, clumping and subsequent plugging of hair follicle pores • Can be primary event or secondary response to irritation or other factors

6. Etiology - 4 primary Factors • Bacterial growth and colonization • Propionibacterium acnes, a partial anaerobe, resides in the normal flora of the follicle • Titers of antibodies to P. acnes are higher in patients with severe acne than non-acne control subjects • Inflammation and immune response • Inflammation is a consequence of increased sebum production, keratinocyte sloughing, and bacterial growth • P. acnes can trigger inflammatory acne lesions

7. Pathophysiology • Sebaceous glands, predominant on the face, chest and upper back respond to androgen stimulation • These glands provide sebum to the follicular canal and eventually the skin surface through the follicular opening • Canal contents contains kertinocytes, P. acnes , and free fatty acids

8. Formation of the Open Comedo The black or brown color of the lesion is NOT the result of dirt accumulation, but rather that of melanin (pigment)

9. Open Comedo

10. Formation of Closed Comedo • Also known as “whitehead” • Results from inflammation or trauma to the follicle • If the follicular wall is damaged or ruptured, the contents of the follicle can extrude into the dermis • Presents as pustule • Clinically important as they become larger, inflammatory lesions secondary to P. acnes • Can take months to heal • Fibrosis associated may cause scarring

11. Closed Comedo

12. Closed Comedo

13. Clinical Presentation

14. Inflammatory Lesions

15. Inflammatory Lesions Papule Nodule Pustule

16. Acne Severity

17. Approach to Treatment • Primarily to prevent the formation of new acne lesions • Have minimal impact on existing lesions • Factors that determine treatment: • Severity • Lesion type • Scarring • Skin discoloration • Previous treatment history • Most treatments can take up to 8 weeks to produce visible results • Acne can appear to worsen during the first few weeks of therapy • Existing lesions will resolve more rapidly

18. Patient Education • Goals • Realistic expectations • Dangers of overtreatment • Do not squeeze comedones • Medication side effects • Daily cleansing • Gentle non-drying cleansing agents

19. Non-Pharmacologic Therapy • Scrubbing with abrasive scrubs or excessive face washing does not necessarily open or cleanse pores • May lead to skin irritation • Cleansing has relatively small impact on treatment for acne • Important to use non-drying cleansing agents

20. Choice of Topical Therapy Ointments are not typically included due to their occlusive nature

21. Pharmacologic Therapy

22. Acne Treatment Algorithms

23. Benzoyl Peroxide • Used to treat superficial inflammatory acne • Non-antibiotic antibacterial agent • Rapidly bacteriostatic • Possibly bacteriocidal • MOA • Antibacterial  decomposed by cysteine, liberating free O2 radicals that oxidize bacterial proteins • Comedolytic activity  increases sloughing rate of epithelial cells & loosens the follicular plug structure • Available in soaps, lotions, creams, washes and gels • Gels are most potent and cause more dryness and irritation • Concentrations range from 1-10% • Efficacy does not necessarily increase with concentration, but side effects do

24. Benzoyl Peroxide • Addition of 10% urea may help to moisturize skin • Fair or moist skin may be more sensitive to irritation • Apply to dry skin or at least 30 mins after washing • Frequency should be no more than twice a day • To reduce irritation, begin with lower concentration • Discontinue if excessive irritation or allergy occurs • Can bleach or discolor some fabrics • Tolerabiliy and efficacy are enhanced when used in combination with other agents such as topical retinoids, clindamycin, and erythromycin

25. Tretinoin • Topical vitamin A analogue • MOA • Increases cell turnover in the follicular and decreases cohesiveness of cells • Leads to extrusion of existing comedones and inhibition of the formation of new comedones • Can reduce the number of inflammatory acne lesions • Available strengths: • Solution: 0.05% (most irritating) • Gels: 0.01% and 0.025% • Creams: 0.025%, 0.05%, and 0.1% (least irritating) • Start with… • Mild acne with easily irritated non-oily skin: 0.025% cream • Moderate acne with easily irritated oily skin: 0.01% gel • Moderate acne with non-sensitive oily skin: 0.025% gel

26. Tretinoin • Concomitant use with antibacterial agent can decrease keratinization, inhibit P. acnes, and decrease inflammation • Has additive or synergistic benzoyl peroxide effects in the treatment of inflammatory acne • Benzoyl peroxide QAM and tretinoin QPM • Enhanced efficacy, decreased irritation • Can increase tolerance by slowly increasing frequency • Can increase sensitivity to sun, wind, cold and other irritants • Teratogenicity risk with topical retinoids remains controversial (Pregnancy class C) • It is rapidly metabolized by the skin

27. Adapalene • Third generation retinoid • Available strengths: • 0.1%: gel, cream, alcoholic solution, pledglets • 0.3%: gel • MOA • Selective affinity for retinoic acid receptor (RAR) subtypes RAR-β and RAR-γ found in the epidermis • Has comedolytic, keratolytic, and anti-inflammatory activity • Indicated for mild to moderate acne • Use 0.1% gel as an alternative to tretinoin 0.025% for better tolerability in some patients • Co-administer with topical or oral antibiotic for moderate forms of acne • Can be alternative in patients of color  less irritation  less subsequent discoloration Pregnancy Class C

28. Tazarotene • Prodrug and synthetic acetylenic retinoid • MOA: • Selectively binds to RAR • Can alter expression of genes involved in cell proliferation, cell differentiation, and inflammation • Comedolytic, keratolytic, and antiinflammatory action • Used in treatment of mild to moderate acne • Available strengths: • Cream: 0.1%, 0.05% • Gel: 0.1%, 0.05%

29. Tazarotene • Once daily 0.1% tazarotene gel is more effective than: • 0.025% tretinoin gel and 0.1% tretinoin gel microsphere in reducing non-inflammatory acne lesions • Once daily adapalene 0.1% gel in reducing both inflammatory and non-inflammatory lesions • Appearance of perilesional irritation can limit use • Dose related local adverse effects • Erythema, pruritus, stinging, burning • Pregnancy Class X • Recommended that negative pregnancy test be obtained 2 weeks prior to starting therapy • Treatment should begin during normal menstrual period

30. Erythromycin • Topical formulation in concentrations of 1% and 4% • With or without addition of zinc • Combination with benzoyl peroxide has been shown to more effective than with tretinoin • Reduces resistance of P. acnes • Usually applied BID • Available in gel, lotion, solution and disposable pad • MOA: • Decreases P. acnes • Reduces inflammation • Decreases percentage of free fatty acids in sebum • Side effects: dryness and irritation

31. Clindamycin • MOA • Inhibits P. acnes • Comedolytic • Anti-inflammatory • Available in gel, lotion, solution, foam, disposable pad formulations • Applied BID • Combination with benzoyl peroxide increased efficacy • Side effects: • Skin dryness and irritation • Rare: diarrhea and psuedomembranous colitis

32. Azelaic Acid • MOA • Antibacterial • Anti-inflammatory • Comedolytic • Used for mild to moderate acne in patients who do not tolerate benzoyl peroxide • Useful in treating postinflammatory hyperpigmentation • Available strengths: 20% creams, 15% gel • Apply BID on clean, dry skin to acne prone areas • No likelihood of bacterial resistance, systemic adverse effects or photosensitivity reactions • Side effects: (usually transient) • Burning, pruritus, stinging, tingling

33. Salicylic Acid • MOA: keratolytic, mildly antibacterial • Evidence for the treatment of acne is conflicting • Can be less irritating than benzoyl peroxide and tretinoin, however it is not as effective a comedolytic agent • May have risk of salicylism from repeated and widespread use on highly permeable skin • Sweating • Vomiting • Tinnitus • Blurred vision • Confusion • Hyperventilation

34. Isotretinoin • Oral retinoid • MOA • Decreased sebum production (most effective sebosuppresive agent) • Inhibition of P. acnes growth • Anti-inflammatory • Altered patterns of keratinization (dec size and inc differentiation) • Treatment of choice • Severe nodulcystic acne • Pts who fail conventional therapy • Acne with scarring • Chronic relapsing acne • Acne and associated pyschological stress • Available strengths: 10mg, 20mg, 40mg tabs • Dosing: 0.5-1mg/kg/day in 2 divided doses for 15-20 weeks or until total cysts count is decreased by 70%

35. Isotretinoin • Adverse effects • 90% experience mucocutaneous effects • 80% experience cheilitis and skin desquamation • Depression • Alopecia (reversible) • Hypertriglyceridemia and hypercholesterolemia (reversible)

36. Isotretinoin • Severe adverse effects • creatinephosphokinase •  blood glucose • Photosensitivity • Pseudotumorcerebri • Hepatomegaly with abnormal LFTs • Bone abnormalities • Arthralgias • Muscle stiffness • Headaches • Teratogenicity Pregnancy class X (iPledge) • Do not breast feed on medication or for 1 month after using medication

37. MacrolideAbx (Oral) • MOA • Anti-inflammatory • Erythromycin • Used for pts who can’t tolerate or acquire resistance to tetracycline • Dosage 1gm/day with meals • Efficacy similar to tetracycline, but higher rates of resistance • Decrease resistance when used with benzoyl peroxide • Azithromycin • Moderate to severe acne • Dosed 3 times per week or once per week, 500mg • Used in combination with oral retinoid as effective as daily doxy • Clindamycin • Although effective, seldom used due to incidence of pseudomembranous colitis

38. Tetracyclines • MOA • Reduce P. acnes • Reduce amount of keratin in sebacous follicles • Anti-inflammatory • Used in treatment of moderate to severe acne • Resistant bacteria may develop • Do not combine with systemic retinoids because of increased probability of intracranial hypertension

39. Tetracyclines • Adverse effects • Hepatotoxicity • Predisposition for superinfections (vaginal candidiasis) • Photosensitivity • GI upset • Risk of inhibition of skeletal growth and discoloration of teeth • Pregnancy category D • Do not use during lactation • Do not use in children under 10

40. Tetracyclines • Tetracycline • Least expensive • Often initial therapy • 500mg BID, 1 hour prior to meals • After 1-2 months, may decrease dose to 500mg daily for 1-2 months • Doxycycline • More effective than tetracycline • Produces less resistance • Initial dose 100-200mg daily, followed by 50mg daily maintenance • Can be taken with food, more effective taken 30 mins prior to meal

41. Tetracyclines • Minocycline • More effective than tetracycline • Dosed similar to doxy, 100mg/day or 50mg BID • Because of amino side chain has ability to cause: • Hypersensitivity syndromes, • Serum sickness-like illness • Discoloration of the skin, nail and bone • Cutaneous hyperpigmentation of at least four distinct types: • Blue-black pigmentation confined to sites of scarring or inflammation of the face • Blue-gray circumscribed pigmentation of normal skin of the lower legs and forearms • Diffuse muddy brown pigmentation of normal skin accentuated in sun-exposed areas • Circumscribed blue-gray pigmentation within acne scars confined to the back

42. Oral Contraceptives • Those containing two agents, an estrogen an progestin, are used as alternate treatment for moderate acne in women • FDA approved agents: • Norgestimate with ethinylestradiol • Norethindrone acetate with ethinylestradiol • MOA • Decrease androgen effect  decrease sebum production • Adverse effects • Nausea and vomiting • Breast tenderness • HA • Spotting and breakthrough bleeding • Edema • Decreased libido • Increased appetite • Weight gain • Increase risk of VTE  especially in women over 35 who smoke!

43. Evaluation of Therapy • Typically acne flares when initial treatment is started • May take up to 8 weeks for full benefits of therapy • Assessment of patient in 1 month to see improvements and assess adverse effects • F/u again usually at month 3,6,12 at least depending on therapy, progress and tolerability • See text for some sample plans

44. Psoriasis

45. Definition • Psoriasis is hyperproliferation of epidermal keratinocytes combined with inflammation of the epidermis and dermis

46. Epidemiology • Affects nearly 7 million Americans and 1-5% of the world’s population • Accounted for approximately 14 million physicians visits over a 12 period between 1990-2001 • Occurs in all racial groups, but more prevalent in Caucasians • Equal among men and women • Two peaks of onset: • Between 20-30 years of age (greatest incidence) • 50-60 years of age • Although rarely life-threatening, adverse emotional and physical impact on QoL

47. Types of Psoriasis

48. Types of Psoriasis

49. Etiology • Most people with psoriasis have at least one immediate relative with the disorder • Aggravating factors: • Climate • Stress • Alcohol • Smoking • Infection • Trauma (Koebner response) • Drugs • Lithium carbonate • BB • Anti-malarial • NSAIDS • Tetracycline

50. Pathophysiology • In psoriatic lesions, T cell migrate into the epidermis where they would not usually be present • Cytokine production of TNF-α, IL-23, IL-20, TGF-α, TGF-β, amphiregulin, IL-1, IL-6, and IL-8 • Result of pathogenic T cell production and activation: • Psoriatic epidermal cells proliferate at a rate 7-fold faster than normal • Duration of epidermal cell cycle is also nearly 8 times faster than normal