1. Acne Vulgaris and Rosacea Dr. Lyn Guenther University of Western Ontario

2. Objectives State the incidence of acne Discuss the psychosocial impact of acne & scarring Discuss the pathophysiology of acne Differentiate acne vulgaris from rosacea Elicit a history and perform a relevant examination Give an approach to acne and rosacea treatment from mild to severe

3. Acne vulgaris Incidence: 95% Scarring - In 95% seeing a dermatologist for the first time - Increased with: Squeezing Inflammatory lesions Longer disease duration

4. Psychological Scarring QOL studies: - Social, psychological & emotional deficits comparable to: Asthma Epilepsy Diabetes Mellitus Back Pain Arthritis

5. Pilosebaceous Unit Sebaceous Gland Sebum Follicle Arrector Pili Muscle 900 glands/cm 2 on face, back, chest <100 glands/cm 2 on rest of body

6. Pathogenesis of Acne Abnormal Keratinization (genes) Androgens cause increased sebum production Propionibacterium acnes Inflammation

7. Acne Vulgaris Pathophysiology Microcomedones Accumulation of Sebum Closed/Open Comedones (non-inflammatory acne) Proliferation of P. acnes Infiltration of neutrophils Ruptured comedones Papules, Pustules, Cysts (inflammatory acne)

8. Acne vulgaris - History Age of onset Family history of acne Location and severity of lesions Scarring Psychosocial impact Menses/Contraceptive use Moisturizer and foundation Medications & Drug Allergies Current and Past treatment including response and A/E’s

9. Physical Examination: Scarring and Pigmentary Changes Scarring: depressed / ice pick / saucer / keloid Excoriations Hyper / hypo-pigmentation Lesion Morphology Non-inflammatory Comedonal Inflammatory Papules / pustules Nodules / cysts

10. Acne Lesions Comedones Papules & Pustules Cysts

11. Acne vulgaris - Why treat? Improve appearance Minimize scarring Eliminate discomfort of inflammatory lesions Reduce psychological consequences

12. Acne vulgaris - Dispel myths Acne is NOT caused by: - Chocolate - Fried or fatty food - Too much or too little sex - Dirt - Wrong kind of soap Not contagious

13. Acne vulgaris - Aggravating Factors Stress Lack of sleep Tight headbands/helmets Grease-filled environments Heavy makeup while exercising Premenstrual in some

14. Acne vulgaris - Cleansing Wash BID Lukewarm water Mild cleanser No abrasives No scrubbing Don’t squeeze

15. Acne vulgaris Moisturizers and Foundation Non-comedogenic Non-acnegenic

16. Treatment Guidelines Non-scarring acne * Comedones: Retinoid * Tretinoin cream.01-.05% daily or * Tazarotene cream/gel or * Differin cream/gel * Papules/Pustules * Topical antibiotic B.I.D. * Benzoyl peroxide 5% daily * Antibiotic/benzoyl peroxide * Oral antibiotics * Hormonal agents for women desiring oral contraception

17. ANTIBIOTIC DOSE Tetracyclines Tetracycline 500 mg B.I.D. Minocycline 100 mg/day Doxycycline 100 mg/day Erythromycin 500 mg B.I.D. Trimethoprim 100 - 200 mg/day NOTES *Avoid in pregnancy or children < 8 years *Take on empty stomach *G.I. irritation *May be taken with food *Dizziness may develop at higher dos es *Pigmentary changes *May be taken with food *Phototoxicity a potential problem *Safe in pregnancy and for children *May caus e G.I. Ups et *Useful in those resistant to other antibiotics

18. Hormonal Therapies for Acne Diane-35® cyproterone acetate/ ethinyl estradiol Ortho -Tricyclen® norgestimate/ ethinyl estradiol Alesse® levonorgestral/ ethinyl estradiol Yasmin ® drospirenone-ethinyl estradiol

19. Treatment Guidelines Severe or Scarring acne Isotretinoin: * 0.5mg/kg/day for the first 2-4 weeks * 1 mg/kg /day for the next 4-5 months to a total cumulative dose of 120-150 mg/kg * 80% have long-term drug free remission * 20% require a second course * patients unable to take isotretinoin should be given topical therapy combined with systemic antibiotics or hormonal agents

20. Isotretinoin Sebaceous follicles Decreases sebum production within 2 weeks Corrects follicular hyperkeratinization Decreases growth of P. acnes Decreases inflammation Pre-Accutane On Accutane

21. Isotretinoin Contraindication: Absolute: Pregnancy (see Pregnancy Prevention Program™) Relative: History of pre-morbid depression History of hypertriglyceridemia/ hypercholesterolemia Pre-existing liver disease

22. Accutane use and pregnancy Isotretinoin is a potent teratogen - >25% risk of fetal malformation. Reported pregnancy rate on Accutane<1% - Average age: 26 years. Reasons for these pregnancies: - abstinence unsuccessful - use of ineffective method of contraception - contraceptive used inconsistently - unexpected sexual activity - failure of contraceptive method

23. Pregnancy Prevention Program™ Two negative pregnancy tests required before starting Accutane - Initial visit & day 2-3 of next period Two effective forms of birth control - one primary and one secondary Begin therapy on 2nd or 3rd day of next menses

24. Pregnancy Prevention Program™ One month prescription only Monthly pregnancy testing Monthly contraceptive counseling Initial Consent form Patient Information booklet

25. Effective Forms of Contraception Primary Tubal ligation Partner’s vasectomy Birth control pills Injectable/implanted hormones IUD Secondary Diaphragms with spermicide Latex condoms with spermicide Cervical caps with spermicide

26. Isotretinoin Adverse Events Cheilitis 96% Dermatitis 55% Dry nose 51% Eye irritation 11% Joint pain 13% Depression rare Elevated TG (25%) & cholesterol (7%) Elevated liver enzymes (15%)

27. Isotretinoin and Psychiatric Events DepressionSuicide/attempt Isotretinoin Use (1982-2000) USA General Pop’n (CDC 1980-92) 10-13 per 100,000 patients 20,000 per 100,000 patients 1-1.7 per 100,000 patients 20 per 100,000 patients

28. Isotretinoin Mucutaneous adverse events: Chapstick Lubricants Lab monitoring: CBC, liver function and fasting lipids Pregnancy test

29. Case studies

30. Case 1 Washes with apricot scrub Has tried numerous other cleansers Has stopped eating chocolate No other treatment

31. Case 2 Won’t socialize Regular menses Not sexually active No prior treatment

32. Case 3 Oily skin Seborrheic dermatitis Plucks facial hair Irregular menses Proactive-No help

33. Case 4 Acne lesions hurt Tetracycline 500 mg BID for 6 months, then Minocycline 100 mg BID for 8 months Differin gel x14 months

34. Rosacea ~10% of Canadians affected Women: Men=2:1, but men more prone to rhinophyma Celtic descent - Uncommon in Africans & Asians Onset usually after age 30 - Peak: 4 th to 7 th decade - Rarely in children Konshik PC et al. Dermatol Clin 1992;10(3):533-47

35. Rosacea Pathophysiology Genetic Abnormalities of cutaneous vasculature - Dysregulation of thermal mechanisms Dermal matrix degeneration - Poor connective tissue support for cutaneous vessels Infectious organisms - Demodex - Helicobacter pylori Excess of canthelicidins and protease stratum corneum tryptic enzyme (STCE) in facial skin Yamaski K et al. Nat Med 2007;13:975-80

36. Rosacea Pathophysiology Murine model: - Injection of cathelicidins found in rosacea or addition of SCTE → skin inflammation - Deletion of the serine protease inhibitor gene Spink5 → protease activity → skin inflammation - TCN + Minocycline indirectly inhibit serine proteases and work even in the face of bacterial resistance Hypothesis: Increase in local antimicrobial peptide expression may change the normal skin microflora in rosacea Yamaski K et al. Nat Med 2007;13:975-80

37. Rosacea affects QOL Recent Canadian Survey (n=1271) : - Social life affected in 36% 16% of all respondents declined a social invitation due to rosacea symptoms Lower self esteem Affects professional interactions

38. Rosacea: Skin changes Symmetric over convexities of central face - nose, cheeks, chin, central forehead Occ. on neck, scalp, chest Very rarely on back and limbs

39. Rosacea: Skin changes Primary features: - Flushing: Usually lasts > 10 minutes Sparing of periocular skin Often assoc. with burning, stinging - Persistent Erythema - Telangiectasia - Papules, pustules (follicular and non- follicular) …….. NO COMEDONES

40. Rosacea: Skin changes Secondary features: - Burning or stinging - Lowered threshold for irritation from topical substances - Plaques - Dry appearance - Edema (e.g. periorbital, glabellar, malar) Acute, chronic recurrent, chronic persistent Pitting or non-pitting - Ocular - Peripheral location (neck, chest, scalp, ears, back)

41. Subtypes of Rosacea 1. Erythematotelangiectatic 2. Papulopustular 3. Phymatous 4. Ocular

42. Phymatous Variant Men Erythematous, irregularly swollen, bulbous, dilated pores, telangiectasia - Rhinophyma (nose) - Metophyma (forehead) - Gnathophyma (chin) - Blepharophyma (eyelids) - Otophyma (ears) Aloi F et al. JAAD 2000;42:468-72

43. Rosacea-Ocular 50% of patients 6 th -7 th decade (later than skin) Women=Men Onset with skin: 2 - 53% skin first - 20% eyes first - 27 % together Strong correlation with flushing 3 1. Barankin B, Guenther L. Can Fam Physician. 2002;48:721-4. 2. Borrie P. Br J Ophthalmol 1953:65:458. 3. Wilkin JK. Int J Dermatol 1983;22:393-400.

44. Rosacea-Ocular Dry, gritty eyes, itching, burning, tearing, blurry vision, photophobia Blepharitis (93%), conjunctival hyperemia (86%), conjunctivitis, keratitis, superficial punctate keratopathy (41%), keratoconjunctivitis sicca (up to 40%) corneal vascularization ulceration and perforation, iritis (20%), chalazion (22%) ~ 60% of patients with chalasion have rosacea Barankin B, Guenther L. Can Fam Physician. 2002;48:721-4.

45. Rosacea Triggers Food: - Hot food - Spicy food - Tomatoes - Chocolate - Yogurt, sour cream,cheese Alcohol Hot and cold temperatures Wind Exercise Stress

46. Rosacea Triggers Drugs: 1 - Corticosteroids - Amiodarone Rosacea + multiple chalazia 2 - Epidermal growth factor receptor inhibitors - High dose vitamin B6 and B12 1.Crawford GH et al. JAAD 2004;51:327-41 2.Reifler DM et al. Am J Ophthalmol 1987;103:594-5

47. Rosacea Treatment Avoid triggers Flushing: - Clonidine 0.05 mg OD→BID - Green moisturizers Telangiectasia - Vascular lasers (e.g. pulsed dye, KTP, 532 and 810 light-emitting diode (LED), Alexandrite, Nd-TAG, IPL alone or with PDT)

48. Rosacea Treatment: Topical Mild cleansers Sunscreen: titanium dioxide & zinc oxide well tolerated Topical - Metronidazole - Azelaic acid 15% (Finacea) - Sodium sulfacetamide 10%/sulfur 5% - Clindamycin - Dapsone - Pimecrolimus/Tacrolimus - +/- BP, VAA (phymatous rosacea; may irritate) Eye: - Warm soaks, dilute baby shampoo - Topical steroids (ophthalmologist) - Artificial tears:

49. Rosacea Treatment: Oral Oral antibiotics (skin + eye) - Tetracyclines: Tetracycline Minocycline Doxycycline - Others: Erythromycin Clarithromycin Azithrmycin Metronidazole Dapsone Isotretinoin (skin including phymas + eye)

50. Rosacea Treatment: Rhynophyma Medical: Isotretinoin Surgical: - Ablative lasers - Shave excision - Cryosurgery - Electrosurgical loops to shave off excessive tissue, then fine tune with dermabrasion

51. www.rosaceainfo.com