acne vulgaris discussion[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

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  • Acne vulgaris: overviewIntroduction:

    Definition:Multi-factorial disease characterized by abnormalities in sebum production, follicular desquamation, bacterial proliferation and inflammation.

    Prevalence:85% adolescents experience itPrevalence of comedones (lesions) in adolescents approaches 100%affects 8% of 25 - 34y yr olds, and 3% of 35-44yr olds

  • OverviewAcne 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.

  • Overview affects all races and ethnicities with equal significance

    Darker skinned patients at increased risk for developing post-inflammatory hyper-pigmentation and keloids.

  • Pathogenesis:

    Acne vulgaris is a disease of pilosebaceous follicles.

    Factors:Retention hyperkeratosis.

    Increased sebum production.

    Propionibacterium acnes

    within the follicle.


  • Initial pathogenesis (reason unknown):follicular hyperkeratinization proliferation + decreased desquamation of keratinocytes

    hyperkeratotic plug(microcomedone)

  • PathogenesisSebaceous glands enlarge

    Sebum production increases

    Growth medium for P. Acnes

    plugs provide anaerobicLipid-rich environment

  • PathogenesisBacteria thrive

    Inflammation results

    Chemotactic factors attract neutrophils

    Depending on conditions

    Non-inflammatory open/closed comedones

    Inflammatory papule/pustule/nodule

  • Terms/DefinitionsMicrocomedone:

    hyperkeratotic plug made of sebum and keratin in follicular canal

  • Closed comedones (whiteheads)closed comedo

    (a whitehead):

    Accumulation of sebum converts amicrocomedo into this.

  • Closed comedones (whiteheads)

  • Open comedo (blackhead)open comedo

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

  • Open comedo (blackhead)

  • Whitehead and blackheads

  • CystsCysts:

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

  • Cysts

  • Pustular

  • KeloidsWell-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

  • keloids

  • PathogenesisMost pts with acne likely have glands locally hyper-responsive to androgens. Other factors can cause increased androgen productionHigher 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

  • PathogenesisAcne may develop de novo in adulthood. Post-adolescent acne predominantly affects women (76%):

    -hyperandrogenous -family history in half -premenstrual flares in older womenadolescent acne has a male predominance

  • External factors:

    Oils, greases, or dyes in hair productsCosmetics water-based products are less comedogenic Repetitive trauma may worsen inflammationSoaps decrease sebum but do not alter productionHumidityperspiration

  • 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.

  • ClassificationClassification 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

    Type 4 Numerous large cysts on the face, neck, and upper trunk; severe scarring

    Note: categories are not rigid. A pt with mainly comedones and papules but notable scarring may be considered to have severe acne

  • DiagnosisComplete historyPay attention to endocrine function

    Rapid appearance with virilization/menstrual irregularity PCOS and other syndromesComplete medication listPhysical exam:

    Location- scarringLesion type - keloidpigmentation

  • Medications that can cause acne ACTHAzathioprineBarbituratesIsoniazidLithiumphenytoin

    DisulfiramHalogensIodidesSteroidsCyclosporineVitamins B2,6,12

  • Treatmentof Acne Vulgarisdepends on type of clinical lesionsChoose vehicle for topical rx acc to pts skin type. (gel for oily, cream for dry skin).Microcomedone matures in 8 weeks

    Therapy must continue beyond this time frameconsiderable heterogeneity in the acne literature, and no clear evidence-based guidelines are available

  • 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

  • Comedonal acneTopical retinoids:Normalize keratinizationonly 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

  • Issues with topical retinoidsPhotosensitivity use in pm, sunscreen

    Local irritation start lowest strength.

    Pustular flare during first few wks of Rx sign of accelerated resolution.

  • Comedonal acneOther topical agents:

    Useful when topical retinoids not tolerated

    Salicylic acid (promotes desquamation)Azelaic acid (antimicrobial, reduces hyperpigminetation)Gycolic acidSulfur in OTC rx (keratolytic)

  • Comedonal acneMechanical removal of comedones useful adjunct to topical rx

  • 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.

  • Mild to moderate inflammatory acneTopical antibiotics Eliminate P. AcneReduce inflammation

    ClindamycinErythromycinTetracyclineMetronidazoleAzelaic acid

  • Moderate to severe acne:

    If topical Rx not effective oral isotretinoin

    oral antibiotics hormonal rx

    Oral isotretinoinReduces sebaceous gland size/sebum productionregulates cell proliferation and differentiationEffect last 1 yr after cessationOnly med altering course of A. Vulgaris

  • Moderate to severe acne:oral isotretinoinAdverse 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 rxPregnancy 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. (manufacturermust commit to 2 contracept.)

  • Monitoring parameters: CBC w/ diff, ESR, glucose, Chol, TG, LFT, CPKObtain baseline, then regular intervals.

    LFT 1-2 x week until response to rxLipids 1-2 x week until response to rx.

  • Moderate to severe acne:

    Oral antibiotics

    -Tetracycline- erythromycin - minocycline- TMP-SMX - doxycycline- clindamycin

    Given daily over 4-6 mo, with taper.

  • 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

  • Moderate to severe acne:

    Hormone rxUnresponsive acneSend for Gyn eval if hirsutism/menstrual irregularities.Consider adult onset congenital adrenal hyperplasia, ovarian/adrenal tumour, Cushings dz /syndrome, PCOS (hirsutism, acne, irregular menses, acanthosis nigrans, insulin resistance)

    Anti-androgens (spironolactone, flutamide, ketoconazole, cimetidine)estrogenMin 3-6 mo of rx

  • Blue light therapy moderate inflammatory acneFDA approvedsmall 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

  • Laser therapyConflicting data on pulsed dye laser rxRandomized 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.

  • CostsMinocycline

    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)

  • Patient FAQsSoaps, detergents remove sebum but do not alter productionAvoid occlusive clothingWater based cosmetic better than oil basedDiet modification no role in rx