Acne vulgaris: overview

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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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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.

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Overview

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

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Pathogenesis

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

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Initial pathogenesis (reason unknown)

• follicular hyperkeratinization
• proliferation
• decreased desquamation of keratinocytes
• hyperkeratotic plug
• (microcomedone)

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Pathogenesis

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

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Pathogenesis

• Bacteria thrive
• Inflammation results
• Chemotactic factors attract neutrophils
• Depending on conditions
• 
  

Non-inflammatory open/closed comedones
Inflammatory papule/ pustule/nodule
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Terms/Definitions

• Microcomedone
• hyperkeratotic plug made of sebum and keratin
  in follicular canal

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Closed comedones (whiteheads)

• closed comedo
• (a whitehead)
• Accumulation of sebum
• converts a
• microcomedo into this.

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Closed comedones (whiteheads)
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Open comedo (blackhead)

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

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Open comedo (blackhead)
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Whitehead and blackheads
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Cysts

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

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Cysts
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Pustular
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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

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keloids
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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

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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

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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

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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.

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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    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

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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

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Medications that can cause acne

• ACTH
• Azathioprine
• Barbiturates
• Isoniazid
• Lithium
• phenytoin

• Disulfiram
• Halogens
• Iodides
• Steroids
• Cyclosporine
• Vitamins B2,6,12

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Treatmentof Acne Vulgaris

• depends on type of clinical lesions
• Choose 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 frame
• considerable heterogeneity in the acne
  literature, and no clear evidence-based
  guidelines are available

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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

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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

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• 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.

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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)

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Comedonal acne

• Mechanical removal of comedones
• useful adjunct to topical rx

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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.

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Mild to moderate inflammatory acne

• Topical antibiotics
• Eliminate P. Acne
• Reduce inflammation
• Clindamycin
• Erythromycin
• Tetracycline
• Metronidazole
• Azelaic acid

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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

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Moderate to severe acneoral 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. (manufacturermust
  commit to 2 contracept.)

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• 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.

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Moderate to severe acne

• Oral antibiotics
• -Tetracycline - erythromycin
• - minocycline - TMP-SMX
• - doxycycline - clindamycin
• Given daily over 4-6 mo, with taper.

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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

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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, Cushings dz
  /syndrome, PCOS (hirsutism, acne, irregular
  menses, acanthosis nigrans, insulin resistance)
• Anti-androgens (spironolactone, flutamide,
  ketoconazole, cimetidine)
• estrogen
• Min 3-6 mo of rx

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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

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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.

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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)

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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