acne vulgaris: overview

1. 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% affects 8% of 25 - 34y yr olds, and 3% of 35-44yr olds

3. Overview affects all races and ethnicities with equal significance Darker skinned patients at increased risk for developing post-inflammatory hyper-pigmentation and keloids.

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

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

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

7. Pathogenesis Bacteria thrive Inflammation results Chemotactic factors attract neutrophils Depending on conditions

8.

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

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

11. Closed comedones (whiteheads)

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

13. Open comedo (blackhead)

14. Whitehead and blackheads

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

16. Cysts

17. Pustular

18. Keloids Well-demarcated overgrowths of scar tissue Altered connective tissue response in predisposed individuals (darker skin), abnormal fibroblast activity. Most commonly on earlobes, chest, upper back, shoulders Can be permanent, pruritic and painful

19. keloids

20. Pathogenesis Most pts with acne likely have glands locally hyper-responsive to androgens. Other factors can cause increased androgen production Higher serum levels of DHEA-S are found in pre-pubertal girls with acne Acne tends to resolve in the third decade as DHEA-S levels decline Medication induced

21. Pathogenesis Acne may develop de novo in adulthood. Post-adolescent acne predominantly affects women (76%): -hyperandrogenous -family history in half -premenstrual flares in older women adolescent acne has a male predominance

22. External factors: Oils, greases, or dyes in hair products Cosmetics water-based products are less comedogenic Repetitive trauma may worsen inflammation Soaps decrease sebum but do not alter production Humidity perspiration

23. External factors: Role for diet in acne is controversial A study of 47,355 women that used a retrospective data found an association between acne and intake of milk - natural hormonal components of milk? A study of 22 university students found in a multivariate analysis some correlation with stress.

24. Classification Classification system generally as follows     Type 1 — Mainly comedones with an occasional small inflamed papule or pustule; no scarring present     Type 2 — Comedones and more numerous papules and pustules (mainly facial); mild scarring  Type 3 — Numerous comedones, papules, and pustules, spreading to the back, chest, and shoulders, with an occasional cyst or nodule; moderate scarring

25. Diagnosis Complete history Pay attention to endocrine function Rapid appearance with virilization/menstrual irregularity ?PCOS and other syndromes Complete medication list Physical exam: Location - scarring Lesion type - keloid pigmentation

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

27. Treatmentof Acne Vulgaris depends on type of clinical lesions Choose vehicle for topical rx acc 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

28. Comedonal acne: Process -increased sebum + abnormal desquamation. To reduce sebum production no other effective rx apart from hormonal therapies or oral isotretinoin Hence Rx of abnormal keratinization is most effective

29. Comedonal acne Topical retinoids: Normalize keratinization only agents that affect terminal differentiation of follicular epithelium. initial drugs of choice All transretinoic acid (tretinoin): C/I in pregnancy. Adapalene gel (no studies for pregnancy) Isotretinoin (tazoretene) : keratolytic, C/I in pregnancy

30. Issues with topical retinoids Photosensitivity – use in pm, sunscreen Local irritation – start lowest strength. Pustular flare during first few wks of Rx sign of accelerated resolution.

31. 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)

32. Comedonal acne Mechanical removal of comedones useful adjunct to topical rx

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. Monitoring parameters: CBC w/ diff, ESR, glucose, Chol, TG, LFT, CPK Obtain baseline, then regular intervals. LFT 1-2 x week until response to rx Lipids 1-2 x week until response to rx.

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

39. Moderate to severe acne: Practices to reduce resistance Use abx if absolutely necessary Concomitant use of B.P. may reduce resistance If abx are stopped and need to be restarted, prescribe the same abx

40. Moderate to severe acne: Hormone rx Unresponsive acne Send for Gyn eval if hirsutism/menstrual irregularities. Consider adult onset congenital adrenal hyperplasia, ovarian/adrenal tumour, Cushing’s dz /syndrome, PCOS (hirsutism, acne, irregular menses, acanthosis nigrans, insulin resistance) Anti-androgens (spironolactone, flutamide, ketoconazole, cimetidine) estrogen Min 3-6 mo of rx

43. Blue light therapy moderate inflammatory acne FDA approved small uncontrolled trial of biweekly rx for 5 wks showed 64% lesion reduction expensive; eight treatments generally cost the patient $800 to $1600 Further data needed to recommend it

44. Laser therapy Conflicting data on pulsed dye laser rx Randomized of 41 assigned to sham or laser showed sig improvement after 12 wks. Second randomized trial (June 04) of similar laser rx comparing sham to laser on either side of face showed no such benefit. Further data needed.

45. Costs Minocycline 100 mg (30): $21.99 to $160 Benzoyl peroxide 5% gel 90 gm : $22 (3-11$/mo for qd) Erythromycin 2% gel 60 mg: $38.65-57 (19-28$/mo qd)

46. 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