2. Acne vulgaris: overview Introduction: Definition: Multi-factorial disease characterized by abnormalities in sebum production, follicular desquamation, bacterial proliferation and inflammation. Prevalence: 85% adolescents experience it Prevalence of comedones (lesions) in adolescents approaches 100%

3. Overview Acne vulgaris is the most common cutaneous disorder in the U.S. It affects more than 17 million Americans. 10 percent of all patient encounters with primary care physicians. Pts can experience significant psychological morbidity and, rarely, mortality due to suicide. Important that physicians are familiar with Acne Vulgaris and its treatment.

4. Acne Vulgaris Asked questions concerning acne. How does acne develops ? Factors for development of acne What are the predisposing factors Is it familiar? Is it controllable. Is it associated with diet or dust? Does cosmetic cause acne. Does drugs cause acne. Does stress has any role in causation of the acne ?

5. Pathogenesis: Acne vulgaris is a disease of pilosebaceous follicles. Factors: Retention hyperkeratosis. Increased sebum production. Propionibacterium acnes within the follicle. Inflammation

6. Etiology, signs and symptoms Acne vulgaris commences in the pilosebaceous units in the dermis. These units consist of hair follicle and the associated sebaceous glands. They are connected to the skin by a duct(infundibulum) through which the hair shaft passes. Non inflamatory acne; ( acne that characterized by closed and open comedones ) The cause of acne is an increase in the activity of the sebaceous glands and the epithelial tissue lining the infundibulum.

7. Etiology, signs and symptoms The glands produce more sebum causing increased oiliness of the skin. The epithelial cells become more distinct,durable and stick together to form a coherent horny layer which blocks the follicular channel. This impaction plugs distends the follicle to form a microcomedo NB, normally epidermal cells continually sloughs off and moves to the surface of the skin with the sebum.

8. continue As more cells and sebum are added, the comedo becomes visible (whitehead) and is called a closed comedo, is., its content do not reach the surface of the skin. If plug enlarges and protrudes from the orifice of the follicular canal, it is called an Open comedo, its contents open to the surface of the skin. The tip may darken (blackhead) because of the accumulation of melanin that is produced by the epithelial cells of the follicular lining.

9. Initial pathogenesis (reason unknown): follicular hyperkeratinization proliferation + decreased desquamation of keratinocytes hyperkeratotic plug (microcomedone)

10. Pathogenesis Sebaceous glands enlarge Sebum production increases Growth medium for P. Acnes plugs provide anaerobic Lipid-rich environment

11. Pathogenesis Bacteria thrive Inflammation results Chemotactic factors attract neutrophils Depending on conditions Non-inflammatory open/closed comedones Inflammatory papule/ pustule/nodule

13. Terms/Definitions Microcomedone: hyperkeratotic plug made of sebum and keratin in follicular canal

14. Closed comedones (whiteheads) closed comedo (a whitehead): Accumulation of sebum converts a microcomedo into this.

15. Closed comedones (whiteheads)

16. Open comedo (blackhead) open comedo (a blackhead): when follicular orifice is opened + distended. Melanin + packed keratinocytes + oxidized lipids  dark colour

17. Open comedo (blackhead)

18. Whitehead and blackheads

19. Inflammatory acne Acne characterized by inflammation surrounding the comedones, papules, pustules, and nodulocystic lesions. it may cause permanent scarring. Inflammatory acne begins in closed comedones, rarely in open ones. As the micro comedo develops, it.distends the follicle, which cause thinning of the walls. primary inflammation of the follicle wall develops with the disruption of the epithelium and infiltration of lymphocytes in to the adjacent area of the dermis. Normal sebum does not contain free fatty acids and is nonirritating, however, in the presence of biolytic enzymes produced by C.acne), triglycerides of the sebum are split and release fatty acids which are irritating to the tissue. Thus sebum contribute to inflammation of the surrounding tissue. The inflamed follicle or pustules either heal in about a week or develop in to cyst or sterile abscesses, which can lead to scaring.

20. Cysts Cysts: when follicles rupture into surrounding tissues, resulting in papule/pustule/nodule.

21. Cysts

22. Aggravating factors Change in sebaceous activity and hormonal level (e.g. before or during premenstrual cycle) High humidity conditions Local irritation or friction Rough or occlusive clothing Cosmetics( having greasy base) Diet; chocolate, nuts, fats colas, or carbohydrates. Oils greases, or dyes in hair product.

23. Strategy for treatment of acne Treatment must be long term however symptoms can be reduced and permanent scaring can be minimized.) it involves: * Removal of excess sebum by washing the affected areas three times a day with warm water and soap. *Topically applied oils and fats e.g. in cosmetics should be eliminated. * Prevention of pilosebaceous orifice closure by use of mild irritants. the irritant effect causes an increased rate of turnover of the epithelial cells lining the follicular duct. Peeling agents also cause keratolysis, which reduces the cohesiveness of the follicular lining.

24. Medications that can cause acne ACTH Azathioprine Barbiturates Isoniazid Lithium phenytoin Disulfiram Halogens Iodides Steroids Cyclosporine Vitamins B2,6,12

25. Treatment of Acne Vulgaris depends on type of clinical lesions Choose vehicle for topical drug according to pt’s skin type. (gel for oily, cream for dry skin). Microcomedone matures in 8 weeks Therapy must continue beyond this time frame considerable heterogeneity in the acne literature, and no clear evidence-based guidelines are available

26. Ingredients in OTC products Sulfur; precipitated or colloidal, 2-10 % other forms, such as zinc sulfide or sodium thiosulfate, are milder. Sulfur presents a paradox in that it helps resolve formed comedones but may promote the formation of new ones. Due to this comedogenic effect, the use of salicylic acid or resorcinol is preferred. Resorcinol and salicylic acid;

27. continue Combination of resorcinol and salicylic acid in ethanol solution is advantageous because it dries quickly and does not leave a visible film. Benzoyl peroxide;(5to 10% cream)a primary irritant which increases the growth rate of epithelial cells, causing an increased rate of sloughing and promoting resolution of comedones, Salicylic acid is used in concentration of o.5 to 2%. Applied at night after washing the affected area with soap and water. Resorcinol(1to 4%) may produce a dark brown scale on some black- skinned people; reaction is reversible when the condition is discontinued. NB, the drug may produces a feeling of warmth, slight stinging, and reddening of the skin. If this action is excessive the preparation should be removed with soap and water and not reapplied until the next day. It should not be used on the eye lids, lips, or neck.

28. Tretinoin Transe retinoic acid The acid form of vitamin A, is a strong primary irritant, similar to benzoyl peroxide, but is more effective. It is available as solution in aqueous gel base (0.05%). Or as cream (0.1%). The products are applied at night. They cause a feeling of warmth or slight stinging. Optimum results occur in3 to 4 months. NB. Care should be taken to avoid touching with eyes, nose, and mouth with tretinoin. Should not used with other keratolytic Should not be applied to wet skin as it cause excessive irritation Exposure to strong sunlight should be avoided because of the increased sensitivity of the skin,. Does not cause the toxic effects of a large doses of vitamin a

29. Tetracycline and some other antibiotics orally administered reduce bacterial population and the concentration of the fatty acids in the sebaceous follicle. Topical antibacterial agents generally are ineffective, because acne is not an infection. These agents can not reach the anaerobic C. Acnes which are found in the deeper areas of the follicle.

30. Oral tetracycline Acne is not an infection, so topically antibacteril agent are ineffective, these agents cannot reach in the deeper areas of the follicles( to the anaerobic coryn bacterium acne) ERYTHROMYCIN: 2% solution in 2:2:1 mix of ethanol- ethylene glycol monomethyl ether + propylene glycol. NB, erythromycin reduce level of fatty acid of the follicles to the level reached by the oral tetracyclin Why ? It is lipid soluble antibiotics which can penetrate the sebaceous follicle to suppress c. bacterium acne Both oral tetracyclin and local erythromycin are prescription drugs only.

31. Effect of sunlight Is often beneficial in acne conditions, due to the irritant properties of the UV rays. Secondary formulation factors.. Lotion and creams, are generally used as the vehicles to carry anti acne medication to the skin. They should have a low fat content so that they do not counteract drying and peeling..ethyl or isopropyl alcohol added to the liquid preparations and gels hastens their drying to a film.

32. Comedonal acne Other topical agents: Useful when topical retinoids not tolerated  Salicylic acid (promotes desquamation)  Azelaic acid (antimicrobial, reduces hyperpigminetation)  Gycolic acid  Sulfur in OTC rx (keratolytic)

33. Mild to moderate inflammatory acne Benzoyl peroxide: (antimicrobial, anticomedonal, pregnancy risk C) Topical antibiotic Combination of both Combination rx more effective than mono in increased inflammatory lesions.

34. Mild to moderate inflammatory acne Topical antibiotics Eliminate P. Acne Reduce inflammation  Clindamycin  Erythromycin  Tetracycline  Metronidazole  Azelaic acid

35. Moderate to severe acne: If topical Rx not effective  oral isotretinoin  oral antibiotics  hormonal rx Oral isotretinoin Reduces sebaceous gland size/sebum production regulates cell proliferation and differentiation Effect last 1 yr after cessation Only med altering course of A. Vulgaris

36. Moderate to severe acne: oral isotretinoin Adverse effects can be severe: Inc TG, teratogenic, bone marrow suppression, hepatotoxicity, top 10 drugs for suicide/depression reports. FDA practice rules: 2 negative pregnancy tests before rx Pregnancy test each month ( bring pt in) physicians need authorization before prescribing Pregnancy risk pts must use 2 contraceptive for at least 1 mo prior to rx. ( manufacturer—must commit to 2 contracept.)

37. Moderate to severe acne: Oral antibiotics -Tetracycline- erythromycin - minocycline- TMP-SMX - doxycycline- clindamycin Given daily over 4-6 mo, with taper.

38. Patient FAQs Soaps, detergents remove sebum but do not alter production Avoid occlusive clothing Water based cosmetic better than oil based Diet modification no role in rx