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.

Inflammation

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