Transcript Mark Jansen, M.D.

ACNE VULGARIS
Diagnosis, Classification and
Treatment
Mark T. Jansen MD
Disclosures
“I have nothing to
disclose”
Mark T. Jansen MD
Acne
Incidence and Prevalence
• Most common in 15 to 42 yo range
• Affecting up to 100% age 12 to 17
• In US, 50 million experience acne
each year
• Approximately 7.7 million acnerelated visits in US each year
Cost
• Yearly, 2.2 billion spent on acne
care in US
• 1.7 billion on prescriptions
• 320 million on OTC products
• Other costs related to office visits
Etiology
• Increased sebum production
• Increased proliferation and
decreased desquamation of
keratinocytes
• Propionibacterium acnes in follicles
(anaerobic diphtheroid, normal flora)
• Comedone formation / inflammation
Pathogenesis
• Adrenarche (prepubertal rise in
DHEA-S)
• Sebaceous gland hypertrophy
• Increased sebum production
• Sebum-growth medium P. acnes
• Proliferation of P. acnes surface
proteins-inflammation by
triggering humoral and cellmediated immune response
Etiology Misconceptions
• “Blackheads are caused by dirt
and poor hygiene”
• “If you wash harder, you wouldn’t
have acne”
• “You have acne because you eat
too much chocolate”
Etiology Misconceptions?
• Milk – Nurses Health Study
(47,000) women.
• Insulin Growth Factor (IGF) - Acne
• Milk high in IGF
• > 3 portions of milk/week
associated with ^ incidence Acne
• High glycemic foods ^ IGF
Etiology Misconceptions?
• Family History - > 3 fold risk if 1st
degree family member had acne
• Stress – No affect on sebum
production but severity worse with ^
stress, especially males
• BMI – Positive association - ^ BMI
with ^ risk of acne for females only
Types of Lesions
• Microcomedone – Precursor of the
clinical lesions of acne (8 wks. to
mature)
• Closed comedone
• Open comedone
• Inflammatory papule
• Inflammatory pustule
• Inflammatory nodule
Microcomedo
Closed Comedone
Open Comedone
Inflammatory Papules
Inflammatory Pustules
Inflammatory Nodules and
Nodulocystic Acne
(cystic acne conglobata)
Treatment
• Who is the “patient”?
• “Buy in” by patient
• Simpler regimen better than
complex
• Cost of therapy considerations
Treatment
• Pustules can be converted to
nodules and papules quickly
• Inflammation and Post-inflammatory
hyperpigmentation (PIH) slower to
improve
• Establish realistic timetable and
treatment end-point
• Consider long term consequences of
the disease – trivial/short term
vs. significant long term (scarring)?
Psychosocial “Complications”
of Acne
Psychosocial “Complications”
• Acne correlated with higher rates
of:
Depression
Anxiety
Social withdrawal
Poor self esteem
Suicide ideation
Overall quality of life
General Guidelines
Negotiate patient “buy in”
Establish realistic goals of treatment
Simplify regimens
Consider cost of therapy
Inquire about OTC products that may ^
side effects or sabotage therapy
• Encourage water-based lotions,
cosmetics and hair products (less
comedogenic) over oil-based products
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Treatment
• Most effective treatment addresses core
factors promoting disease:
Follicular hyperproliferation and abnormal
desquamation
Increased sebum production
Propionibacterium acnes (P. acnes)
proliferation
Inflammation
Pathogenesis Specific Agents
Follicular hyperproliferation and
abnormal desquamation
Topical Retinoids (Tretinoin,
Adapalene and Tazarotene)
normalize follicular hyperkeratosis
and normalize desquamation which
prevents formation of micorcomedo
Pathogenesis Specific Agents
Topical Retinoids
Vitamin A derivatives bind to
receptors in keratinocytes
Normalize follicular keratinization
Decrease cohesiveness of
keratinocytes reducing follicular
occlusion and microcomedo formation
Pathogenesis Specific Agents
Topical Retinoids
Anti-inflammatory effects
Bind specifically to receptors that
down regulate formation of proinflammatory protein AP-1 and
expression of toll-like receptor (TLR)2
Pathogenesis Specific Agents
Topical Retinoids
Accelerate resolution of acneinduced post-inflammatory
hyperpigmentation (PIH)
PIH more common in patients with
darker complexions
Pathogenesis Specific Agents
Topical Retinoids
Tretinoin (Retin-A, Retin- Micro and
generics)
Adapalene (Differin and generics)
Tazarotene (Tazorac – no generic
psoriasis – pregnancy X)
Pathogenesis Specific Agents
Topical Retinoids
Pearls of application
Tretinoin (Retin-A) photo labile so
night-time application preferred
Only 19% stable 2 hours after UV
sunlight exposure
Pathogenesis Specific Agents
Topical Retinoids
Pearls of application
Avoid tretinoin with benzoyl
peroxide
Oxidizes tretinoin especially with
light exposure, inactivating drug
Pathogenesis Specific Agents
Topical Retinoids
Pearls of Application
Adapalene (Differin) and tretinoin gel
microsphere (Retin-A Micro) more
light stable
Adapalene more stable in presence of
benzoyl peroxide (combo Epiduo)
Pathogenesis Specific Agent
Agent
Pro
Con
Tretinoin
Generic available, multiple
strengths 0.01% gel, 0.025%
cream/gel, 0.05% cream,
0.1% cream
Degraded by light and
benzoyl peroxide.
Avoid in pregnancy.
gels more irritating than
creams
Adapalene
Generic available in 0.1%
cream/gel. Trade name
only in 0.1% lotion, 0.3%gel.
Light stable. Less irritating.
Can be used with BP
Some formulations trade
name only. Avoid in
pregnancy
Tazarotene
Psoriasis and acne. Best
for PIH. Most effective.
Available in 0.05% and 0.1%
cream or gel
No generic currently. Most
irritating. Pregnancy
category X
Pathogenesis Specific Agents
Retinoid Intolerance
Irritation, dryness and flaking,
worse in 1st month
Avoid concomitant harsh soaps,
toners, astringents, alpha hydroxy
acids and salicylic acids
Pathogenesis Specific Agents
Retinoid Intolerance
Consider application every 2nd or 3rd
night
Avoid “typical” soaps which have a
pH of 9 to 10. Use synthetic
detergent cleansers with a pH of
5.5 to 7 (Cetaphil, Dove Sensitive
Skin Bar)
Pathogenesis Specific Agents
Retinoid Intolerance
For true retinoid intolerance,
consider alternatives:
Azelaic acid – 15% gel (Finacea)
and 20% cream (Azelex).
Antimicrobial, comedolytic and
anti-inflammatory comparable
efficacy to tretinoin 0.05% cream
Pathogenesis Specific Agents
Retinoid Intolerance
Alternatives continued:
Salicylic acid. Induces keratolysis.
Available in gel and pads with 0.5%
and 2% as well as multiple products
(cream, cloths, foam, cleansers,
patches, pads, soaps, shower gels)
of 2% concentration
Pathogenesis Specific Agents
Sebum production and the role of
Androgens
DHEA-S – Testosterone – DHT (all in
the sebaceous gland)
DHT attaches to receptors in the
sebaceous gland that upregulate
sebum production
Pathogenesis Specific Agents
Anti-androgenic agents
OCAs – Low dose combination
products estrogen dominant which
makes them “anti-androgenic”
Drospirenone containing pills (Yazmin
and Yaz) may be superior in antiandrogenic effect (potassium sparing
– monitor potassium during 1st cycle)
Pathogenesis Specific Agents
Third generation progestins
Norgestimate
Desogestrel
(Less androgenic)
Gestodene
Second generation progestins
Levonorgestrel
Norethindrone (More androgenic)
Pathogenesis Specific Agents
Progestin-only Contraceptives
Androgenic
Low dose (mini-pill)
Medroxyprogesterone injections
Levonorgestrel IUD (Mirena)
Etonogestrel implant (Implanon)
Pathogenesis Specific Agents
Androgen Receptor Blockers
Spironolactone – Blocks androgen
receptors and inhibits androgen
biosynthesis (off-label use)
50 to 100mg/day in two divided
doses
Pathogenesis Specific Agents
Spironolactone (continued)
Monitor for hyperkalemia and
hypotension at 4 and 6 wks.
Black box warning (tumorigenic in
chronic toxicity animal studies)
Pregnancy category C – feminization
of male fetus. Strongly consider OCAs
Pathogenesis Specific Agents
Antimicrobials
Reduce Colonization of P. acnes
Topical antimicrobials
Oral antimicrobials (antibiotics)
Pathogenesis Specific Agents
Topical Antimicrobials
Benzoyl peroxide (antimicrobial and
comedolytic)
Clindamycin
Erythromycin
Sulfacetamide
Dapsone
Pathogenesis Specific Agents
Benzoyl peroxide
Available in US in both Rx and OTC in 2.5%
up to 10% gels, lotions, bars, pads, masks
and liquid cleansers
Applied BID
Higher concentration not necessarily
better. Higher concentrations more
irritating and all may bleach hair/clothing
Pathogenesis Specific Agents
Clindamycin
1% concentrations in gel, solution,
lotion, foam and pledgets
Not effective as monotherapy. Use in
combination with either retinoids or
benzoyl peroxide to increase efficacy
and reduce bacterial resistance.
Pathogenesis Specific Agents
Clindamycin
Generic widely available in all forms
Topical may be irritating. Prolonged use may
predispose to fungal or bacterial
superinfections including C. difficile. Warn to
notify if patient develops diarrhea or bloody
stool. Less likely than with oral form
Pregnancy risk B
Pathogenesis Specific Agents
Erythromycin
2% concentrations in gel and solution
formulations
Avoid monotherapy. Consider
combination with retinoid or benzoyl
peroxide to increase efficacy and
decrease bacterial resistance
Pathogenesis Specific Agents
Erythromycin
Generic widely available in all
forms
May be irritating. Minimal systemic
absorption. Potential for GI side
effect minimal. Pregnancy risk B
Pathogenesis Specific Agents
Sulfacetamide
Typically combined with 5% sulfur
Not usually 1st line therapy
Avoid in patients with allergy to
sulfa or sulfonamide
Pathogenesis Specific Agents
Sulfacetamide
Widely available as 10% gel, liquid,
suspension, cream, lotion and pads
Pregnancy risk C. Consider
avoiding in potentially fertile
females
Pathogenesis Specific Agents
Dapsone
Topical 5% dapsone gel is newest
topical antimicrobial that also has
anti-inflammatory activity
Unlike oral dapsone, no practical
concern for use in individuals with
G6PD deficiency. No associated
hemolytic anemia or methemoglobinemia issues
Pathogenesis Specific Agents
Dapsone
Not a sulfa. Not contraindicated in
sulfa allergic patients
Applied BID. No generic. May
discolor skin/hair yellow-orange
when used with benzoyl peroxide
Pathogenesis Specific Agents
Combination Topical Therapy
Combination topical therapy shown to
be more effective than monotherapy
Evidence-based confirmation of
superior efficacy of topical retinoids
in combination with topical
clindamycin, erythromycin or benzoyl
peroxide
Pathogenesis Specific Agents
Combination Topical Therapy
Two fixed antimicrobial / retinoid
combinations available in US
Clindamycin 1.2% / tretinoin 0.025%
gel (Ziana, Veltin)
Benzoyl peroxide 2.5% / adapalene
0.1% (Epiduo)
Pathogenesis Specific Agents
Combination Topical Therapy
Resistance to topical antibiotics now
widespread
No resistance of P. acnes to benzoyl
peroxide yet
Combining topical antibiotics with benzoyl
peroxide decreases development of
resistance and improves treatment
efficacy
Pathogenesis Specific Agents
Combination Topical Therapy
Topical benzoyl peroxide / antibiotic
combinations in US:
BP 5% / clindamycin 1% gel (Benzaclin,
Duac)
BP 5% / erythromycin 3% gel (Benzamycin)
BP 2.5% / clindamycin 1.2% gel (Acanya)
Pathogenesis Specific Agents
Topical Therapy
Azelic acid – antimicrobial, comedolytic
and anti-inflammatory properties
20% cream (Azelex), 15% gel (Finacea approved in US for rosacea only) applied
BID
Equally efficacious to tretinoin 0.05%
cream, BP 5% gel or 2% erythromycin
Pathogenesis Specific Agents
Oral Antibiotics
Indicated for moderate to severe
inflammatory acne
May be used for patients with
milder acne of the trunk where
application of topicals are more
problematic
Pathogenesis Specific Agents
Oral Antibiotics
Inhibit growth of P. acnes in
pilosebaceous unit
Tetracycline class have anti-inflammatory
properties too
Systemic antibiotics tend more rapid
clinical improvement than topicals but
carry risk of more side effects
(candidiasis, GI distress, significant
allergic or toxic reaction)
Pathogenesis Specific Agents
Oral Antibiotics
Prescribe for a limited course of 3 to
6 months to reduce risk of antibiotic
resistance
Consider discontinuation as acne
improves
No consensus as stopping systemic
drug abruptly or in tapering fashion
Pathogenesis Specific Agents
Oral Antibiotics
Tetracyclines (doxycycline,
minocycline)
Macrolides (erythromycin,
azithromycin)
Trimethoprim-sulfamethoxazole
Clindamycin
Pathogenesis Specific Agents
Oral Antibiotics
Emerging resistance of P. acnes
20% in 1978. 62% in 1996
Most common with erythromycin
Least common with minocycline
Pathogenesis Specific Agents
Oral Antibiotics
Reducing emergence of resistance:
Use only when necessary. Limit
treatment to < 6 mos. Stop if no
additional improvement noted
Give choice a minimum of 6 to 8
weeks (length of time-microcomedone
to mature clinical lesion)
Pathogenesis Specific Agents
Oral antibiotics
Reducing resistance continued:
Change after 6 to 8 weeks if no
response
Partial response – continue 1st choice
and reassess in 6 to 8 more weeks
Pathogenesis Specific Agents
Oral Antibiotics
Reducing resistance continued:
If stopped antibiotic needs to be restarted and was
effective, resume same drug as long as works
Avoid combination therapy with oral and topical
antibiotics that have different mechanism of action
Prescribe topical BP at start of oral antibiotic
therapy
Pathogenesis Specific Agents
Oral Antibiotics
Reducing resistance continued:
Consider topical retinoid at initiation of
oral antibiotic. Decreases resistance and
more efficacious
Consider topical retinoids for long term
maintenance to decrease oral antibiotic
use and sustain improvement
Pathogenesis Specific Agents
Oral Antibiotics
Macrolides – Erythromycin,
azithromycin
Resistance now common
GI side effects
Consider only in patients where
tetracyclines are contraindicated
Pathogenesis Specific Agents
Oral Antibiotics
Tetracyclines – Hard to get
tetracycline. Inactivated by food
Doxycycline / minocycline not affected
by food. Have anti-inflammatory
effects. Minocycline has less
resistance than doxycycline but
generally higher cost
Pathogenesis Specific Agents
Oral Antibiotics
Tetracyclines continued:
Avoid < 9 yo and women who are or may
become pregnant – teeth
GI distress
Esophagitis
Pseudotumor cerebri, vertigo (minocycline)
Photosensitivity, skin or liver discoloration
Pathogenesis Specific Agents
Oral Antibiotics
Subantimicrobial doxycycline
Maintains anti-inflammatory activity
without antibacterial effect
Maintains improvement in
inflammatory acne without inducing
resistance. 20mg BID
Pathogenesis Specific Agents
Oral Antibiotics
Alternative oral antibiotics
Trimethoprim – sulfamethoxazole
Effective in more severe,
recalcitrant acne but with
associated risk of photosensitivity,
bone marrow suppression and
Stevens-Johnson syndrome
Pathogenesis Specific Agents
Oral Antibiotics
Clindamycin – Risk of
pseudomembranous colitis (C. diff )
Cephalexin – Little evidence.
Hydrophilic so doesn’t penetrate
pilosebaceous unit well. May
promote MRSA
Pathogenesis Specific Agents
Isotretinoin
Reserved for severe, recalcitrant
nodulo-cystic acne
Restricted prescribing (iPLEDGE)
Severe teratogenic effects
Treatment Algorithm
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1st choice
Alternatives
Alternatives
for females
Maintenance
Summary
Negotiate patient “buy in”
Simplify treatment regimens
Cost conscious
Evidence based
Remember pregnancy potentials
Good “stewardship” of oral
antibiotics
• Psychological considerations
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Summary
Target areas of pathophysiology
Follicular hyperproliferation,
abnormal desquamation
Increased sebum production
P. acnes proliferation
Inflammation