acne

Question 1

Pathogenesis ofAcne

New evidence 1 suggests
inflammation
precedes comedone
formation possibly2

Answer 1

1. Sebum
   production by the
   sebaceous gland
2. Alteration in the
   keratinization
   process
3. C.acnes
   follicular
   colonization

1 or 4. Release
of inflammatory
mediators into
the skin
Acne is a cyclical process

Question 2

Further Investigations

Answer 2

 Usually not required:
 The diagnosis is a clinical one
 Culture and sensitivity of pustules:
 Only appropriate to rule out Gram-negative folliculitis (uniform,
eruptive pustules in the perinasal and perioral region, typically in
the setting of long-term use of tetracycline antibiotics)
 Hormonal investigations may be warranted if there are other
signs of hyperandrogenism such as:
 Hirsutism
 Infertility
 Irregular or infrequent menses
 Insulin resistance
 Middle-age onset in female sex

Question 3

Recognizing the Chronicity of

Acne

Answer 3

Acne should be approached as a chronic disease

“…there is good evidence that acne can persist into
adult years in as many as 50% of individuals”

 Acne has characteristics used to define chronicity:
 Prolonged course
 Pattern of recurrence or relapse
 Manifestation as acute outbreaks or slow onset
 Psychological and social impact on quality of life
 Early and aggressive treatment of acne is necessary to prevent scarring and pigmentation
 Maintenance therapy is recommended for optimal outcomes

Question 4

AcneTreatment Algorithm

Answer 4

Comedonal: topical retinoid, BPO (no diff above 5%

more severe roal isotretinoin -> dont add oral agents to it

see slide 7

Question 5

Retinoids

TOPICAL

Answer 5

 Retinol
 Many OTC products

 Alitretionoin (topical or oral)
 Used for Kaposi’s carcinoma (topical)
 Toctino (oral) – hand excema

 Tretinoin
 Stieva-A, Retin A micro
 0.04%
 0.1%

 Adapalene
 Differin – 0.1%
 Differin XP – 0.3%

 Tazarotene
 Tazorac (topical accutane/isotret, very potent)
▪ 0.05%, 0.1%

Question 6

Retinoids

ORAL

Answer 6

 Isotretinoin
 Accutane
▪ 10 mg, 20 mg, 40 mg
 Clarus
 Epuris

 Acitretin-Etrenate (not
for acne, used for
psoriasis)
 Soriatane

Question 7

Retinoids

fxn

Answer 7

 Retinoids-natural and synthetic analogues of vitamin A
 Retinol
 Tretinoin

 Essential for formation of body tissues such as skin,
bone, vasculature
 Promotion of good vision
 Immune function
 Embryonic development and organogenesis
 Cell proliferation and differentiation
 Apoptosis

Question 8

Mechanism ofAction of

Retinoids

Answer 8

 Act on gene expression by activating 2 families of receptors
 RARs (retinoic acid receptors)
▪ Predominantly affect cellular differentiation and proliferation
▪ E.g. tretinoin, adapalene, tazarotene
▪ Side effects: mucocutaneous and muscoskeletal symptoms
 RXRs (retinoid X receptors)
▪ Predominantly induce apoptosis
▪ E.g. bexarotene and alitretinoin (used in Kaposi’s sarcoma)
▪ Side effects: “physiochemical changes”

 The clinical effects of retinoids in dermatology are related to their
ability to affect pathways involved in inflammation, cellular
differentiation, apoptosis, and sebaceous gland activity.
 Generally, all the interesting effects of retinoids are not completely
understood!

Question 9

Fetal Risk Summaries and

Breast Feeding Compatibilities

Answer 9

typically say no to topical retinoid for pregnancy

evidence changing

Question 10

A NoteAboutAcitretin

 Acitretin (Soriatane®) and Etretinate

Answer 10

 Acitretin is a metabolite of etretinate
▪ Can be converted back to etretinate in the presence of ethanol
▪ Alcohol indirectly enhances the re-esterification of acitretin to etretinate.

 Both are teratogenic
▪ Must avoid pregnancy for 3 years after discontinuation
▪ Prolonged storage in subcutaneous fat (etretinate has a very long t1/2)
▪ Difficult to predict plasma concentrations of both molecules
 Long elimination half lives
▪ 80-160 days for etretinate
▪ ~2 days (50 hrs) for acitretin

Question 11

GeneralAdverse Effects for

Retinoids

Answer 11

 1. Teratogenicity
 Isotretinoin and acitretin must not be taken by patients who are pregnant
or who may become pregnant
 Even with topical retinoids?/ Medicolegal issues?

 2. Hypervitaminosis A
 Dry skin and mucous membranes
▪ Avoid areas around corner of nose, eyes, mouth, mucous membranes
 Epidermal fragility
▪ Use lowest strength possible
▪ Every second night application for topicals and titrate up to daily use
 Visual disturbances
 Hair thinning
 Suggest that patient do not take excess of vitamin A supplements

Question 12

Retinoids AE hypervitaminosis

Answer 12

 Hypervitaminosis Cont’d
 Skin lesions
 Liver toxicity
 Reduced bone density (seen in chronic and higher dosing)
 Photosensitivity
▪ Caution with other drugs that may be photosensitizing
 May increase tumorigenic potential of UV radiation
 Myalgia & arthralgia
 Nail fragility
 Degree of side effects determined by route of
administration and dosing regimen

Question 13

Topical Retinoids-Mechanism

Answer 13

 Vitamin A analogues
 Modifies epithelial growth and differentiation
 Decreases cohesiveness of epithelial cells and
decreases microcomedone formation
 Affects abnormal keratinization, inflammation
 Tretinoin specifically increases turnover of
epithelial cells causing purge of comedones.
 Promotes epidermal thickening, dermal regeneration,
pigment lightening - also used to prevent wrinkles

Question 14

Topical Retinoids use

Adapalene
• Differin 0.1% cream or gel
• Differin XP 0.3% gel
Trifarotene
• Actlief cream
Tretinoin
• Retin-A 0.05% cream, Retin A Micro 0.04 % &
0.1% gel, Stieva-A 0.025% cream
Tazarotene
• Tazorac 0.05% and 0.1% as cream or gel

Answer 14

 3 types prescribed most often:
 Adapalene, tretinoin, tazarotene
 Trifarotene (Aklief) – newest agent on the block
 Each retinoid binds to a different set of retinoic
acid receptors thereby each retinoid has slightly
different activity, tolerability and efficacy
 Potency: ADA< TRE < TAZ (TRI potency uncertain)
 Use:
 Monotherapy or combo formulations for comedolytic
acne
 All forms of acne (inflammatory/non-inflammatory)
when used in combination with other agents

Question 15

Topical Retinoids
contra
administration
response time
AE

Answer 15

Administration Apply topically to entire affected area at bedtime
May apply adapalene in the morning due to less
photosensitivity

Contraindications Pregnancy? Look up current evidence.

Response time May worsen in the first 2-4 weeks, see maximumeffect at 3 months

Adverse effects Erythema, drying, stinging, photosensitization (less with adapalene)

Question 16

topical retinoids

Counseling points

Answer 16

• Use sunscreen SPF 15-30

• To decrease irritation: start on low concentration,
apply every 2-3 nights, work your way up to daily
application
• Pea size dab for entire face
• After successful course can consider stepping down
to less frequent maintenance treatment
• Regular moisturization of the skin
• Stop retinoid 1 week prior to derm procedure or
sunny vacation

Question 17

Combination Formulations

remember active ingredients, not brand names

Answer 17

 Antibiotic + retinoids
 Biacna Gel (clindamycin 1.2% + tretinoin 0.025%)
- could get resistance to clindamycin, there should be BP to mitigate resistance
 Stievamycin Gel (0.01-0.05% tretinoin + 4%
erythromycin)

 Benzoyl peroxide + retinoids
 Tactupump gel (adapalene 0.1%+ BP 2.5%)*
 Tactupump forte gel (adapalene 0.3% +BP 2.5%)*

*Note: BPO has oxidizing action and may inactivate
retinoids/antibiotics so use premixed formulations!

Question 18

Systemic Retinoid: Isotretinoin

mechanism

Answer 18

Mechanism
 Reduces sebaceous gland size and reduces
sebum production
 Targets sebum excretion, keratinization,
inflammation, C. acnes

Most powerful anti-acne agent
 Reliable clearing and sustained remission in even the most
severe cases

Question 19

Systemic Retinoid: Isotretinoin

uses

Answer 19

 Reserve use because of significant adverse effects

 Uses
 Severe nodulystic acne
 Scarring
 Failure to respond to other treatments/ intolerability of prior
systemic therapy
 Significant psychological distress because of acne

Question 20

Isotretinoin Contraindications

Answer 20

Absolute • Pregnancy, lactation, or female

contemplating conception
• Female of childbearing potential non-compliant with contraception
• Not a concern in males, studies
have shown insignificant concentrations of isotretinoin in semen.
• Pregnancy Category X (contraindicated, teratogen)
• Soybean allergy (Accutane, Clarus) epuris ok

Relative
• Moderate to severe dyslipidemia, impact lipid
• Severe liver disease
• Severe kidney disease

Question 21

Isotretinoin

Dosing based on
weight
admin
response time

Answer 21

• Standard daily dose: 0.5-1mg/kg
• Course recommended cumulative dose:
120-150mg/kg
• Course is typically about 6 months (takes 6 mo to get to that dose)
- relapse high if not getting to the cumulative dose

Administration • Once to twice daily with meals

• Increased absorption with high fat meal, note Epuris can be taken without a fatty meal

Response time • May see initial flare first 2 months,
adherence can be an issue!
• Response time ~ 3 months
10mg, 20mg, 40mg capsule Brands:
Accutane, Clarus, Epuris

Question 22

Isotretinoin: Low dose versus standard dosing

Answer 22

 Low dose dosing (<0.4mg/kg or 20mg/day) improves acne similar
to standard dosing (0.5-1mg/kg)
▪ Would still give patient total calculated dose of therapy, spread over a longer
period of time
 Less side effects (chapped lips, dry skin)

 Initial Acne Flare with Isotretinoin
 Initial acne flare up may occur during the first 2 months of tx
(~6% of patients).
 If flare severe: stop ISO, restart at lower dose of 0.1mg/kg/d, &
slowly increase to 0.5mg/kg/d; OR give prednisone 0.5-1mg/kg/d
x 2-3 wks with a gradual taper.

Question 23

Isotretinoin

Drug
interactions

Answer 23

• Tetracyclines***
• Risk: Benign intracranial hypertension (pseudotumor
cerebri)
• Avoid using together
• If transitioning patient from a tetracycline to isotretinoin:
washout period of ~7 days.

• Vitamin A
• Increase risk of additive toxic effects
• Advise against taking supplements with Vit A
• Combined oral contraceptives
• “Decrease effectiveness cannot be ruled out” Patient
should be on 2 forms of contraceptives

• Alcohol
•  risk of hepatotoxicity
• Advise abstaining from alcohol or to drink in moderation
• Concomitant topical therapy
• Generally avoided due to drying effect but consider
maintenance once iso d/c

Question 24

iso monitroing

Answer 24

Pregnancy

• Test for pregnancy twice before initiating treatment,
monthly, and after discontinuation (1 month), blood test to
rule out pregnancy every month (need a negative
pregnancy test before initiating therapy (be sensitive to
patient’s preferences and probability of pregnancy)
• 2 reliable contraception forms are recommended

CBC, LFT, lipids: 0,1, every 3 months
• New approach (slide 33): Lipid and hepatic screen
baseline and repeat in 2 months

Mood
• Monitoring done by patient, family/friends, pharmacist

Question 25

iso Counseling points (not

exhaustive)

Answer 25

• Regularly moisturize skin and lips
• Keep hydrated
• Dryness worst in first 8 weeks  use Vaseline,
eye lubricants, temporary removal of contacts,
nasal lubricants
• Avoid other acne topicals during treatment and a
few months after  increase dryness, avoid makeup
• Avoid intense sunlight, tanning (use sunscreen
everyday minimum SPF 30)
• Avoid waxing during and 5-6 months after therapy
(risk of epidermal stripping, scarring, dermatitis)
• Female: 2 reliable contraception forms are
recommended
• Loss in night vision, stop isotretinoin immediately
and contact prescriber (seeing halos)

Question 26

Should you do monthly labs?

Answer 26

 Lipid and hepatic
screen baseline and
repeat in 2 months

 In female patients
consider regular
pregnancy testing
(monthly) if applicable

Question 27

zAntibiotics

 Topical
oral

Answer 27

 Topical (Clindamycin, Erythromycin)
 Not recommended as monotherapy! Add it to BPO!
 Act directly on C. acnes and reduce inflammation.
▪ Not that great for non-inflammatory lesions (i.e. white heads
and blackheads)

 Oral
 tetracycline, doxycycline, minocycline (1st line)
 erythromycin (2nd line)
 trimethoprim (3rd line))

always add benzoyl peroxide to this regimen (topical)

Question 28

Topical Antibiotics‐ Clindamycin,

Erythromycin

Answer 28

Mechanism Decreases skin colonization of C. acnes

When to use Inflammatory acne

Brands (single ingredient)

Dalacin T 1% solution, Clindets 1% topical pad
Erythromycin gel 1-5%

Administration Apply topically to entire affected area once to twice daily

Response time See improvement 8-12 weeks

Adverse effects Erythema, itching, peeling, dryness, burning
Clindamycin CI: Hx of previous colitis, ulcerative
colitis, pseudomembranous colitis

Question 29

Combination products available

topical abx

Answer 29

Should be combined with topical benzoyl
peroxide to prevent antibacterial resistance
 Combination products available
 Benzaclin, Clindoxyl: benzoyl peroxide 5% +
clindamycin 1%
 Benzamycin: benzoyl peroxide 5% + erythromycin 3%
 Biacna: tretinoin 0.025% + clindamycin 1%

Question 30

Oral Antibiotics: Tetracycline,

Minocycline, Doxycycline

Answer 30

Mechanism • Targets C. acnes

When to use • Moderate to severe acne, acne on back/chest/shoulders, failed topical treatment

Administration • Space 2 hours from milk and multivitamins (tetracycline  empty stomach)

Response time • Allow 8-12 weeks to see response, if no improvement stop

Contraindications • Pregnancy
Adverse effects • Stomach upset, *photosensitivity

• May decr oral contraceptive effectiveness
• *Major concern with long-term therapy= BACTERIAL
RESISTANCE

Other • Patient should use in combination with topical benzoyl peroxide**

Question 31

compare oral abx

Answer 31

Doxycycline 50-100 mg once or twice daily
Apprilon® (40mg daily used
for anti-inflammatory MOA)
**actually subtherpeutic - fro rosacea not acne
• Can be taken with food
• Higher risk of photosensitivity reaction
• Least GI upset

Minocycline 50-100 mg once or twice daily

• Hyperpigmentation (blue-ish) of oral
mucosa and skin; lupus-like reactions,
drug-induced liver toxicity
• Once was favoured by clinicians, but
now there is no clear evidence that it is
superior to tetracycline
• It is also associated with more severe
adverse effects than tetracycline

Tetracycline 250-500 mg once or twice daily

• Inexpensive and well-tolerated
• Needs to be taken on empty stomach
• Not before sleep = esophageal
ulceration

Question 32

Combined Oral Contraceptives
(COC)

 Tri-Cyclen
▪ Ethinyl estradiol (35mcg)/Norgestinate

▪ Alesse
▪ Ethinyl estradiol 20 mcg/Levonorgestrel 100 mcg

 Diane 35
▪ Ethinyl estradiol & cyproterone acetate (androgen blockade)
▪ Lacks contraception indication (CAN)

▪ Yasmin, YAZ, YAZ-Plus
▪ Ethinyl estradiol + drospirenone 3mg
▪ Increased risk of VTE with drospirenone ?

Answer 32

 Mechanism
 Anti-androgenic effect suppresses sebaceous gland activity
 Takes 3-6 months to assess full benefit
 All COCs are beneficial but only some have an official indication
 Progestin-only contraceptives may worsen acne
 Good option in patients that also want a method of contraception
(female use only)
 Overall > 50% improvement in lesions

talk to endocardiologists for those transitioning, can use nonhormonal tx for acne

Question 33

Aldactone (Diuretic)

Answer 33

 Spironolactone
 Anti-androgenic
 Dose: 25-200 mg daily
 Response time: 2-3 months
 Monitor potassium for incr., additional side effects include menstrual irregularity, Gi
upset, headache

NOT AN OCP

Question 34

Topical dapsone

Aczone®

Answer 34

 5% gel applied BID (>12
yo)

 A sulfone with anti-
inflammatory and

antibacterial properties
 Altering action of C. acnes
in the pilosebaceous unit
 Works better in females (?)
 Adverse effects:
▪ Dryness and erythema

Question 35

Topical azelaic acid

Finacea®

Answer 35

 15% gel BID
 Comedolytic and
antibacterial. Does not
promote resistance.
 Can reduce
hyperpigmentation
 Adverse effects:
▪ Mildly irritating

Question 36

Keloid Scarring

Answer 36

 Thick, enlarged scars which are
bigger than the original wound
 More common in people with
darker skin
 Can occur from minor injury or
spontaneously
 Identify:
 Raised, firm to touch,
hairless appearance and
will be similar in colour or
darker than surrounding
skin
 Location: earlobes,
cheeks, upper chest

ask abt hair practices (any cultural routines)

Question 37

maskne

Answer 37

 Due to occlusion of the skin around the
perioral region and jawline
 Hormonally dependent area (more so in
females)
 Development of blackheads and white
heads along the mask line
 Management:
 Non Pharm:
▪ Wash mask frequently
▪ Choose a cotton mask
▪ Follow general care measures as discussed
 Pharm”
▪ OTC Benzoyl Peroxide
▪ OTC Salicylic Acid
▪ Prescription: Topical Retinoid, Topical Dapsone,
BP + Topical Antibiotics