Acne Vulgaris:

Pathophysiology, diagnosis, and treatment of a common

dermatologic condition

Latasha Weeks, B.A., B.S.

Doctor of Pharmacy Candidate, 2007
University of Maryland School of Pharmacy
 Learning Objectives

„ Define acne and describe its epidemiology

„ Explain the pathophysiology of acne
„ Describe the clinical presentation of acne
„ Explain how acne is diagnosed
„ Discuss the various treatment options for acne,
both pharmacologic and non-pharmacologic

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 What is Acne?
„ Acne vulgaris is a chronic, inflammatory disease of the
pilosebaceous units of the skin.

„ Pilosebaceous unit
= hair + hair follicle + sebaceous gland

„ Sebaceous gland
„ Found in hair-covered areas
„ Functions to secrete sebum, an oily substance that acts to protect and
waterproof skin and hair, and keep it from being dry, brittle, and
cracked

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 Epidemiology
„ Age
„ Acne can present at any point during a person’s life
„ Adolescent acne usually presents prior to the onset of
puberty

„ Sex
„ During adolescence, acne is more common in males than
females
„ During adulthood, acne is more common in females than
males

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 Epidemiology cont…
„ US population
„ Acne affects more than 85% of teenagers
„ Results in more than 2 million visits to the doctor per year for patients
15-19 years of age
„ Mean age at presentation for treatment is 24 years
„ 10% of doctor’s visits take place when patients are between the ages of 35
and 44 years.

„ Financial impact
„ Direct cost of acne in the US is estimated to exceed $1 billion per year
„ Of this amount, it is estimated that $100 million is spent on over-the-
counter acne products

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 Epidemiology cont…
„ Psychosocial impact
„ Social, psychological, and emotional impairment that can result from acne
has been reported to be similar to that associated with other chronic
medical conditions like arthritis, asthma, diabetes, and epilepsy

„ Patients are prone to depression, social withdrawal, anxiety, and anger

„ Scarring associated with acne can lead to lifelong problems with regards
to self-esteem

„ Patients with acne are more likely to be unemployed

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The Skin

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 Pathophysiology
„ Primary Causes
„ Increased sebum production
„ Abnormal epithelial desquamation
„ Bacterial growth
„ Inflammation

„ Secondary Triggers
„ Mechanical obstruction (e.g., helmets, shirt collars)
„ Increased hormonal activity (e.g., menstrual cycles, puberty)
„ Stress (due to increased output of hormones from the adrenal gland)
„ Cosmetics and emollients (occlude follicles and cause an acneiform eruption)
„ Medications with halogens (iodine, chlorine, bromine)
„ Lithium, barbiturates, androgens
„ Anabolic steroids

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 1. Increased Sebum Production

„ Maturation of the adrenal gland or an increase in

the number of cells of the sebaceous gland can
lead to excess sebum production

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 2. Abnormal Epithelial Desquamation

„ Hyperkeratinization of the hair follicle prevents the normal

shedding of follicular keratinocytes

„ This results in follicular canal widening and increased cell

production

„ Sebum mixes with excess loose cells in the follicular canal to

form a keratinous plug, or microcomedo
„ “Blackhead” – aka, open comedo; color due to the oxidation of tyrosine
to melanin upon exposure to air
„ “Whitehead” – aka, closed comedo; due to inflammation or trauma to the
follicle

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 3. Bacterial Growth

„ The occluded follicle is rich in lipids as this is a

major component of sebum

„ This environment fosters the growth of

Propionibacterium acnes, a bacteria that is part of
the normal flora of the skin

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 4. Inflammation

„ P. acnes provokes an inflammatory response by

breaking down triglycerides found in sebum to
free fatty acids and glycerol, and these
compounds are proinflammatory

„ P. acnes leads to further inflammation by

releasing chemotactic factors that result in WBC
activity

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 Clinical Presentation
„ Acne may present on the face, neck, chest, back,
shoulders, or upper arms

„ Acne can be described in terms of:

„ Type of lesion
„ Classification of severity

„ Lesions can take months to heal completely, and

fibrosis associated with healing may lead to permanent
scarring

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 Type of Lesion
„ Non-Inflammatory
„ Comedonal
„ “Whitehead” – dilated hair follicle filled with keratin, sebum, and bacteria,
with an obstructed opening to the skin
„ “Blackhead” – dilated hair follicle filled with keratin, sebum, and bacteria,
with a wide opening to the skin capped with a blackened mass of skin debris

„ Inflammatory
„ Papulo-pustular
„ Papule – small bumps less than 5mm in diameter
„ Pustule – small bump with a visible central core of purulent material

„ Nodulocystic
„ Nodule – bump greater than 5mm in diameter

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Severity

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Mild Acne

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Moderate Acne

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Moderately Severe

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Severe Acne

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 Diagnosis

„ The diagnosis of acne is established by

observation of acne lesions

„ The presence of 5-10 comedones is usually

considered to be diagnostic

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 Therapeutic Objectives

„ To prevent the formation of new acne lesions

„ To heal existing lesions

„ To prevent or minimize scarring

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 Treatment Options

„ Non-pharmacologic
„ Surface skin cleansing

„ Pharmacologic
„ Topical products
„ Oral antibiotics

„ Isotretinoin

„ Hormonal agents

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 Non-Pharmacologic Treatment
„ Surface skin cleansing with soap and water has a relatively small
effect on acne because it has minimal impact within follicle

„ Skin scrubbing or excessive face washing does not necessarily

open or cleanse pores and may lead to skin irritation

„ Use of gentle, nondrying cleansing agents is important to avoid

skin irritation and dryness during some acne therapies

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 Pharmacologic Treatment:
Topical Products
„ Benzoyl peroxide
„ Retinoid analogues
„ Topical antibiotics
„ Azelaic acid

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 Benzoyl Peroxide
„ Role in Acne Treatment:
„ Non-antibiotic antibacterial agent that is bacteriostatic against P. acnes
„ Increases the sloughing rate of epithelial cells and loosens the follicular plug structure
„ Proven effective in the treatment of acne

„ Availability
„ Available in a wide variety of dosage forms (e.g., soaps, lotions, creams, washes, and gels)
and dosages (e.g., 2.5% to 10%

„ Dosing
„ To limit irritation and increase tolerability, begin with lowest concentration and increase
either the strength or application frequency
„ Patients should apply the product to cool, clean, dry skin no more than twice daily

„ Common Side Effects

„ Dryness and irritation
„ May bleach or discolor some fabrics

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 Retinoid Analogues

„ Role in Acne Treatment

„ Increases cell turnover in the follicular wall

„ Decreases cohesiveness of cells, leading to extrusion

of the comedones and inhibition of new comedo
formation

„ Effectiveness in the treatment of acne is well

documented

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 Retinoid Analogues cont…
„ Examples
„ Tretinoin (topical vitamin A acid)
„ Availability – wide variety of dosage forms and concentrations, including Retin-A-
Micro
„ Dosing – applied once nightly
„ Side Effects – skin irritation, erythema, peeling, increased sensitivity to sun exposure,
wind, or cold

„ Adapalene (Differin)
„ Availability – 0.1% gel, cream, alcoholic solution, and pledgets
„ Dosing - applied once daily at night or in the morning
„ Side Effects – minimal irritation

„ Tazarotene (Tazorac)
„ Availability – 0.05% and 0.1% gel or cream
„ Dosing – applied once nightly
„ Side Effects – irritation, erythema, burning, stinging

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 Topical Antibiotics
„ Role in Acne Treatment
„ Both erythromycin and clindamycin have demonstrated efficacy and are well
tolerated

„ Availability
„ Wide variety of dosage forms and concentrations
„ Also available in combination with benzoyl peroxide

„ Dosing
„ Erythromycin – applied once or twice daily
„ Clindamycin – applied once or twice daily
„ In combination with benzoyl peroxide – applied once or twice daily

„ Common Side Effects

„ Development of resistance by P. acnes

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 Azaleic Acid
„ Role in Acne Treatment
„ Reported to possess comedolytic, anti-inflammatory, and antibacterial
properties

„ Availability
„ 20% cream

„ Dosing
„ Applied twice daily on clean, dry skin

„ Side Effects
„ Mild transient burning, pruritus, stinging, and tingling

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 Pharmacologic Treatment:
Oral Antibiotics
„ Role in Acne Treatment
„ Standard of care in the management of moderate and severe acne as well as in
treatment-resistant forms of inflammatory acne

„ Examples
„ Minocycline – reserved for patients who do not respond to other oral antibiotics
or topical products; superior to doxycycline in reducing P. acnes
„ Doxycycline – more effective than tetracycline
„ Tetracycline – least expensive and most often prescribed for initial therapy
„ Erythromycin – effective, but use is limited to those who cannot use the
tetracyclines (e.g., pregnant women or children under 8 y.o.)
„ Trimethoprim-Sulfamethoxazole – effective, but use is limited to those who
cannot use the tetracyclines or erythromycin, or in case of resistance to these
antibiotics
„ Clindamycin – use is limited by diarrhea

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 Oral Antibiotics cont…
„ Dosing
„ Minocycline – 50-100mg once to twice daily
„ Doxycycline – 50-100mg once to twice daily
„ Tetracycline – 250-500mg twice to four times daily
„ Erythromycin – 250-500mg twice daily
„ Trimethoprim-Sulfamethoxazole – 160/800mg twice daily
„ Clindamycin – use is limited by diarrhea

„ Common Side Effects

„ Vaginal candidiasis, photosensitivity, diarrhea

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 Pharmacologic Treatment:
Isotretinoin
„ Role in Acne Treatment
„ Indicated for severe nodular or inflammatory acne in patients unresponsive to
conventional therapies, for scarring, for those with chronic relapsing acne, and for
acne associated with severe psychological distress
„ Decreases sebum production, changes in sebum composition, inhibits P.acnes
growth within follicles, inhibits inflammation

„ iPLEDGE
„ This agent is a potent teratogen, and thus should only be prescribed by physicians
knowledgeable in its appropriate administration and monitoring
„ Female patients of child-bearing potential must only be treated with this agent if
they are participating in iPLEDGE, the approved pregnancy prevention and
management program
„ Physician enters the patient’s information into the iPLEDGE website
„ Dispensing pharmacist interviews patient and verifies patient information on
website
„ Patient has to sign a consent form to comply with the program
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 Isotretinoin cont…
„ Dosing
„ 0.5-2.0mg/kg/day
„ Drug is usually given for a 20 week course of therapy
„ Lower doses can be used for a longer time period, with a total cumulative
dose of 120-150mg/kg

„ Common side effects

„ Dry mouth, nose, and eyes
„ Increases in cholesterol, triglycerides, glucose, and transaminases

„ Other reported effects

„ Mood disorders, depression, suicidal ideation,

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 Pharmacologic Treatment:
Hormonal Agents
„ Role in Acne Treatment
„ Estrogen-containing oral contraceptives can be useful in the treatment of
acne in some women

„ Currently FDA-approved products for the treatment of acne include

Ortho Tri-Cyclen (norgestimate with ethinyl estradiol) and Estrostep
(norethindrone acetate with ethinyl estradiol)

„ These products have been shown to be equally efficacious

„ The effect of other estrogen-containing contraceptives (e.g., transdermal

patches, vaginal rings) has not been studied

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 References
„ American Academy of Dermatology: Guidelines of Care for Acne Vulgaris
Management. Access on 11/26/2006 at
http://www.aad.org/professionals/guidelines/guidelines.htm.

„ James WD. Clinical Practice: Acne. N Engl J Med. 2005 Apr 7;352(14):1463-72.

„ Feldman S, Careccia RE, Barham KL, Hancox J. Diagnosis and treatment of acne. Am
Fam Physician. 2004 May 1;69(9):2123-30.

„ Liao DC. Management of acne. J Fam Pract. 2003 Jan;52(1):43-51.

„ Bershad SV. The modern age of acne therapy: a review of current treatment options.
Mt. Sinai J Med. 2001 Sept-Oct;68(4-5):279-86.

„ Federman DG, Kirsner RS. Acne vulgaris: pathogenesis and therapeutic approach. Am
J Manag Care. 2000 Jan;6(1):78-87.

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