Duke Internal Medicine Residency Curriculum
Acne
By Kevin Brown, Jeremy Goodwin, Alice
Gray and Angela Poppe Ries
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Learning Objectives
• Understand the pathogenesis of acne
• Recognize the epidemiology and
prevalence of acne
• Understand the impact acne can have on
a patient’s self esteem and quality of life
• Be able to diagnose acne
• Understand the classifications of acne
• Know the major treatments for acne
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Burden of Disease
Acne
• Affects 17 million Americans
• Most common skin disease
• Can cause disfigurement and permanent
physical scarring
• Can cause emotional and psychological
scarring as well
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Burden of Disease
Acne
•
•
•
•
Mean age of presentation for treatment is 24
Direct cost in US is $1 billion
$100 million in over the counter medication
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 selfesteem
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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 in the stratum corneum
• Sebum contains squalene, wax esters,
triglycerides, sterols and sterol esters.
• Lined by keratinocytes
• Contains hair follicle
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Pathophysiology
Normal pilosebaceous unit:
Image courtesy www.nih.gov
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Pathophysiology
Pathogenesis of Acne: Four key
factors
1.Excess sebum production
2.Comedogenesis
3.Propionibacterium acnes colonization
4.Inflammation
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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)
• Higher rate of sebum production is associated
with lower concentration of linoleic acid in surface
wax esters
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Pathogenesis
Androgen levels and Acne
• Circulating androgen levels are normal in
most people with acne.
– A small proportion of patients with acne
exhibit signs of excessive androgen
production (hirsutism or significant menstrual
dysfunction), but most do not.
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Pathogenesis
2.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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Pathogenesis
Microcomedo
– Earliest microscopic
lesion
– Characterized by
follicular plugging
– No bacteria or
inflammation
Image courtesy of www.nih.gov
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Pathogenesis
3.Propionibacterium acnes
colonization
• Anaerobic diphtheroid
• Part of normal skin flora
• Proliferates inside plugged follicle due to the
specialized microenvironment
• Microcomedo fills with P acnes
• Provokes an immune response through
inflammatory mediators
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Pathogenesis
P. acnes
– Activates toll-like receptor 2 (TLR-2)
– TLR-2 upregulates production and release of
proinflammatory cytokines
• IL-12, IL-8
– TLR-2 expression increases as lesion ages
and becomes more inflamed
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Pathogenesis
4.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 proinflammatory factors that recruit neutrophils
and lymphocytes to follicular epithelium
• Inflammatory cells surround follicle, diffuse
through follicular wall and make enzymes that
disrupt follicular wall
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Pathogenesis
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
J Am Acad Dermatol 1995 May;32(5 Pt 3):S6-14.
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
Subtypes of Acne
• Intrinsic Acne
– Acne Vulgaris – most common
– Acne Fulminans
– Perioral Dermatitis
• Extrinsic Acne
– Acne Cosmetica
– Drug Induced
• Childhood Acne
• Acneiform Eruptions
– Rosacea
– Steroid Acne
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
Childhood Acne
• Neonatal Acne
– Found in 20% of infants
– Spontaneously resolves by 1-3 months
• Infantile Acne
– Appears later
– May last until 5 years of age
– ?increased risk for acne vulgaris
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
Extrinsic Acne
• Acne Cosmetica
– Peak incidence in women ages 20-40
– Cosmetic must be discontinued
• Drug-induced Acne
– Steroid
– Lithium
– Isoniazid
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
Rosacea
• Vascular component of
erythema and telangiectasia
• With or without acneiform
component
• Women>Men
• Peak incidence 30-50yr
• Precipitated by hot
beverages, stress, ETOH,
spicy food
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
Acne Vulgaris
•
•
•
•
Affects >17 million
Peak incidence at puberty
M>F
Close to 100% prevalence
in teenage boys
• Prevalence drops to <5%
in adults age 35-44yrs
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
Racial Differences
• Papules are most frequent presentation in all
groups
• Limited racial & ethnic data about acne
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
Racial Differences
• Blacks are a heterogeneous group
– African, African-American, Afro-Caribbean, and
persons of mixed ethnic background
• Incidence is same as general population
• Blacks are less likely to present with
inflammatory lesions and more likely to have
comedones, both open and closed
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
Racial Differences
• Possible protective role of thicker follicular
epithelium of pilosabeceous units in blacks
– More likely to keratinize and form comedones
– Despite clinically benign appearance
• Biopsy shows marked inflammation
• Higher risk of post-inflammatory hyperpigmentation
• When blacks have inflammatory lesion the
often heal with hypertrophic scarring and
keloids
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Epidemiology of Acne
Epidemiology in Non-Western Society
• Acne rates are considerably lower in non-westernized
societies
• 1200 Kitavan (Pacific Island)
– Including 300 subjects between ages 15-25 years
– no case of acne (grade 1 with multiple comedones or
grades 2-4) was observed.
• 115 Aché subjects (Indonesia)
– Including 15 subject between ages 15-25 years
– no case of active acne (grades 1-4) was observed
• These differences cannot be explained solely on genetic
differences
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Classification of Acne
Classification of Acne Vulgaris
• Can also classify based on type of lesion
– Comedonal (Non-inflammatory)
– Papulopustular or Nodulocystic (Inflammatory)
• Other classification schemes take into
account distribution on the body and scarring
• Patients tend to overestimate severity while
physicians underestimate it
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Topical Treatments
Retinoids: Normalize desquamation of the epithelium, preventing
obstruction of the pilosebaceous outlet. Prevents formation of new
comedones. Maximal response occurs over 12 weeks.
– Tretinoin (Retin-A)
• Is available in generics
• Inactivated by UV light so must be applied at night
• Oxidized by benzoyl peroxide so the two cannot be applied
together
• Retin-A Micro: Slow release form with less irritation
– Adapalene (Differin)
• Superior to tretinoin, equal to Retin-A Micro
• Less irritation
– Tazarotene (Tazorac)
• Superior to tretinoin and adapalene in some studies
• Most irritating
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
ORAL TREATMENTS
• Hormonal therapy
– OCP’s
• 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 OCP’s
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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 longterm 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
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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 but stories in the lay press
have popularized the accutane and suicidal
depression connection
– Heavily regulated
• Prescribing physicians must be registered with the
manufacturer
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
QUESTION 1
1. Your Aunt BettyJo yells at your brother Bud for his “dirty skin
and habits” and tells him this is why he has such bad acne.
Your reply is –
a. Bud IS dirty and he should go scrub his face.
b. Tell Bud he is just stressed with the bull riding competition
looming and that is why he broke out.
c. Calmly, explain to both of them that acne has nothing to do
with dirty skin.
d. You start crying because of all the horrible flashbacks to your
teen years that his conversation has generated.
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
Answer Question 1
C. While you may start crying from your
traumatic, acne-scarred past, the best answer is
C. Acne is not a result of dirty skin, improper
cleansing, stress or other bad habits. Acne is a
disease of the pilosebaceous units. All the
scrubbing in the world won’t cure acne.
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
QUESTION 2
True or false:
Blackheads are dirty whiteheads.
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
ANSWER QUESTION 2
• False. The discoloration of open
comedones, or “blackheads”, is not
dirt. Just remember acne, black
heads, your brother Bud – none of
them have to do with dirt!
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
QUESTION 3
A woman in her twenties comes to clinic concerned about
her moderate acne. She works as a lifeguard. What do
you recommend as a first line agent to treat her acne?
a.
b.
c.
d.
Clindamycin topical gel
Tretinoin ointment
Oral contraceptives
Accutane
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
ANSWER QUESTION 3
C. Oral contraceptives. OCPs are a safe and effective
treatment for acne, especially for patients who are do not
want to get pregnant. Avoid retinoids in this patient who
is out in the sun regularly as it increases photosensitivity.
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
QUESTION 4
An 18 year old man comes to clinic with severe, pustular
acne on his back. He’s getting ready to go off to college
where he will be on the varsity swim team. He’s terribly
embarrassed about his problem and is desperate for help.
You recommend:
a. Benzoyl peroxide wash
b. Aldapalene ointment
c. Tetracycline
d. Isotretinoin
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
ANSWER QUESTION 4
C. Tetracycline. Topical agents may be challenging for this
patient as his symptoms are on his back, and he may
have difficulty reaching the affected area. Accutane is a
possibility, but the physician prescribing it must be
registered with the manufacturer’s System to Manage
Accutane-Related Teratogenicity (SMART) program and
LFTs need to be monitored monthly – not easy to do
when he is off at college. Tetracylcine is a better first line
choice.
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
QUESTION 5
• Topical Antibiotics should generally be combined with
what medicine to avoid inducing bacterial resistance?
A: adapalene
B: benzoyl peroxide
C: isotretinoin
D: antibacterial soap
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
ANSWER QUESTION 5
B. Combining topical antibiotics with benzoyl peroxide can
help mitigate bacterial resistance. While this combo is
good, remember not to combine topical retinoids with
benzoyl peroxide as they are oxidized by benzoyl peroxide
.
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
QUESTION 6
• Concerning isotretinoin therapy, which of the following is
false?
A: Monthly monitoring of LFT’s is required
B: Women must use two forms of birth control while using
isotretinoin
C: Most patients require multiple courses of isotretinoin
D: Isotretinoin is the only therapy that can induce permanent
remission
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
ANSWER QUESTION 6
C. When using isotretinoin therapy, LFTs must be monitored
monthly, the physician prescribing it must be registered
with the manufacturer’s System to Manage AccutaneRelated Teratogenicity (SMART) program, and women
need to be counseled on the dangers of getting pregnant
while on this therapy and then started on birth control.
40% of patients will not need any re-treatment. 40% will
have recurrence but it will be able to be treated with
agents that did not work in the past. 20% may need to
be treated again with isotretinoin therapy.
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services
Duke Internal Medicine Residency Curriculum
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.
Halder RM. Acne in Ethnic Skin. Dermatol Clin 21 (2003) 609-615
Harper JC. An update on the pathogenesis and management of acne vulgaris. J Am Acad Dermatol 2004;51(1):S36-8.
James WD. Acne. N Engl J Med 2005;352:1463-72.
Leyden JJ. New understandings of the pathogenesis of acne J Am Acad Dermatol 1995;32:S15-25.
Loren C. A Disease in Western Civilization. Arch Dermatol. 2002;138:1584-1590.
Taylor CS. Epidemiology of skin diseases in ethnic populations. Dermatol Clin 21 (2003) 601-607
Webster GF. Acne vulgaris. BMJ 2002;325:475-9.
White GM. Recent findings in the epidemiologic evidence, classification, and subtypes of Acne Vulgaris. J Am Acad Dermatol.
1998;39(2, pt 3):S34-S3J
Copyright © 2005, Duke Internal Medicine Residency Curriculum and DHTS Technology Education Services