Acne By Lee so hee

Burden of Disease Acne Most common skin disease Can cause disfigurement and permanent physical scarring Can cause emotional and psychological scarring as well

Burden of Disease Acne Social, psychological and emotional impairment reported to be similar to that associated with epilepsy, asthma, diabetes and arthritis Scarring can lead to lifelong problems with self-esteem

Pathophysiology Acne: A Disease of Pilosebaceous Units Exist all over body except palms and soles Most concentrated on face, chest and upper back Make sebum which maintains hydration of the skin and hair Lined by keratinocytes Contains hair follicle 병이 어떻게 생기고, 어떻게 진행되고, 결국 어떻게 되는가.....

Pathophysiology Normal pilosebaceous unit: Image courtesy www.nih.gov

Pathophysiology Pathogenesis of Acne: Four key factors Excess sebum production Comedogenesis Propionibacterium acnes colonization Inflammation

Pathogenesis 1. Excessive sebum production Due to sebaceous gland hyperplasia Thought to be related to androgen activity, but precise role unclear 5α-reductase type 1 is present in sebaceous gland and converts testosterone to dihydrotestosterone (DHT)

Pathogenesis Comedogenesis: Hyperproliferation of follicular epithelial cells May be related to lower levels of linoleic acid in sebum Prevents normal shedding of follicular keratinocytes Leads to plugging of the follicle and creates a microcomedo Lipid and cellular debris build up within the microcomedo Exact mechanism not understood

Pathogenesis Microcomedo Earliest microscopic lesion Characterized by follicular plugging No bacteria or inflammation Image courtesy of www.nih.gov

Pathogenesis Microcomedones can evolve into: Noninflammatory lesions Closed and open comedones Can remain stable for long periods of time or turn into inflammatory lesions Inflammatory lesions acne pustules, papules, nodules and cysts

Pathogenesis Open and closed comedones Open comedo – “blackhead” – follicular opening reaches skin Dark discoloration is not dirt Closed comedo – “whitehead” follicular opening remains beneath skin Images courtesy of www.nih.gov

Pathogenesis Propionibacterium acnes colonization Anaerobic diphtheroid Part of normal skin flora Proliferates inside plugged follicle Microcomedo fills with P acnes Provokes an immune response through inflammatory mediators

Pathogenesis Inflammation – due to P acnes P acnes hydrolyzes the triglycerides and creates free fatty acids Fatty acids penetrate dermis causing inflammation P acnes also secretes chemotactic and pro-inflammatory factors that recruit neutrophils and lymphocytes to follicular epithelium Inflammatory cells surround follicle, diffuse through follicular wall and make enzymes that disrupt follicular wall

Pathogenesis Inflammation – cont. Follicular wall ruptures and leaks lipids, fatty acids and bacteria into dermis This causes more inflammation and characteristic acne lesions Degree of inflammation may be dependent on individual immune response to P acnes

Pathogenesis

Epidemiology of Acne J Am Acad Dermatol 1995 May;32(5 Pt 3):S6-14.

Epidemiology of Acne Subtypes of Acne Intrinsic Acne Extrinsic Acne Acne Vulgaris – most common Acne Fulminans Perioral Dermatitis Extrinsic Acne Acne Cosmetica Drug Induced Childhood Acne Acneiform Eruptions Rosacea Steroid Acne

Epidemiology of Acne Acne Vulgaris Peak incidence at puberty M>F Close to 100% prevalence in teenage boys Prevalence drops to <5% in adults age 35-44yrs

Epidemiology of Acne Acne Vulgaris in Women As age increase, acne become more common in females than males At age 40, found in 1% of males and 5% of females 70% of females have flare 2-7 days prior to menses Pregnancy can cause flares or improvement Look for PCOS in women with severe acne, irregular menses, hirsutism

Epidemiology of Acne Myths of Acne Vulgaris Eating chocolate or rich/oily foods not associated Skin is not “dirty” – aggressive cleaning does not help No clear association with stress – may be from touching/picking at face while stressed Sunlight never found to improve acne

Classification of Acne Classification of Acne Vulgaris No great classification system Based on 1990 American Academy of Dermatology guidelines Mild Acne – Few to several papules and pustules but no nodules Moderate Acne – Several to many papules and pustules with a few nodules Severe Acne – Numerous papules and pustules as well as several nodules

Classification of Acne Classification of Acne Vulgaris Can also classify based on type of lesion Comedonal (Non-inflammatory) Papulopustular or Nodulocystic (Inflammatory)

Topical Treatments Benzoyl peroxide Generally considered first-line therapy Inexpensive and available over the counter Bactericidal Has not been shown to induce bacterial resistance Primary side effects are skin drying and irritation

Topical Treatments Superior to tretinoin, equal to Retin-A Micro Retinoids: Normalize desquamation of the epithelium, preventing obstruction of the pilosebaceous outlet. Prevents formation of new comedones. Maximal response occurs over 12 weeks. Adapalene (Differin) Superior to tretinoin, equal to Retin-A Micro Less irritation Tazarotene (Tazorac) Superior to tretinoin and adapalene in some studies Most irritating

Topical Treatments Antimicrobials: More effective for inflammatory lesions than retinoids. When used as monotherapy induction of microbial resistance is a major issue. Combination with benzoyl peroxide mitigates this problem. Clindamycin (Cleocin) Erythromycin Sulfacetamide (Klaron) Azelaic acid (Azelex) There are preparations of clindamycin + benzoyl peroxide (BenzaClin) and erythromycin + benzoyl peroxide (Benzamycin) that are available

Oral Treatments Antibiotics: Indicated for moderate to severe disease or in patients for whom topical treatments have failed Erythromycin Has become 2nd line because of microbial resistance Tetracycline Moderate to severe phototoxicity and GI intolerance Cheap Doxycycline Minocycline Potent acne medication Generally reserved for doxycycline or tetracycline refractory cases because of rare but severe side effects TMP-SMX

ORAL TREATMENTS Hormonal therapy OCs Useful adjunct in female patients Decrease circulating androgens, thereby decreasing sebum production Choose a formulation with progestins of low androgenic potential such as norethindrone (Norlutin), ethynodiol (Zovia), and norgestimate (Ortho-Cyclen) Spironolactone Best if used in combination with OCs

ORAL TREATMENTS Isotretinoin (Accutane) Used to treat severe, nodulocystic inflammatory acne Affects all four pathogenetic factors of acne: reduces size and secretion of sebaceous glands inhibits growth of P. acnes reduces inflammation normalizes differentiation of follicular keratinocytes Only treatment that can suppress acne over the long-term and possibly induce permanent remission 40% have remission after one treatment, 40% have a mild recurrence that is responsive to medications that did not work previously, and 20% need retreatment

ORAL TREATMENTS Isotretinoin Continued Side effects Extremely teratogenic (females must be on 2 forms of birth control during use) Monthly monitoring of LFT’s and triglyceride levels is required The link between isotretinoin and depression remains controversial

References Chiu A, Chon SY, Kimball AB. The response of skin disease to stress. Arch Dermatol 2003;139:897-900. Feldman S, Careccia RE, Barham KL. Diagnosis and treatment of acne. Am Fam Physician 2004;69:2123-30, 2135-6.