acne Flashcards

1
Q

Pathogenesis ofAcne

New evidence 1 suggests
inflammation
precedes comedone
formation possibly2

A
  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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Further Investigations

A

 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Recognizing the Chronicity of

Acne

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

AcneTreatment Algorithm

A

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

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

see slide 7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Retinoids

TOPICAL

A

 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%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Retinoids

ORAL

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

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Retinoids

fxn

A

 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Mechanism ofAction of

Retinoids

A

 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!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Fetal Risk Summaries and

Breast Feeding Compatibilities

A

typically say no to topical retinoid for pregnancy

evidence changing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

A NoteAboutAcitretin

 Acitretin (Soriatane®) and Etretinate

A

 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

GeneralAdverse Effects for

Retinoids

A

 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Retinoids AE hypervitaminosis

A

 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Topical Retinoids-Mechanism

A

 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

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
A

 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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q
Topical Retinoids
contra
administration
response time
AE
A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

topical retinoids

Counseling points

A

• 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

17
Q

Combination Formulations

remember active ingredients, not brand names

A

 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!

18
Q

Systemic Retinoid: Isotretinoin

mechanism

A

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

19
Q

Systemic Retinoid: Isotretinoin

uses

A

 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

20
Q

Isotretinoin Contraindications

A

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

21
Q

Isotretinoin

Dosing based on
weight
admin
response time

A

• 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
22
Q

Isotretinoin: Low dose versus standard dosing

A

 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.

23
Q

Isotretinoin

Drug
interactions

A

• 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

24
Q

iso monitroing

A

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

25
iso Counseling points (not exhaustive)
• 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)
26
Should you do monthly labs?
 Lipid and hepatic screen baseline and repeat in 2 months  In female patients consider regular pregnancy testing (monthly) if applicable
27
zAntibiotics  Topical oral
 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)
28
Topical Antibiotics‐ Clindamycin, | Erythromycin
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
29
Combination products available | topical abx
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%
30
Oral Antibiotics: Tetracycline, | Minocycline, Doxycycline
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**
31
compare oral abx
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
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 ?
 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
33
Aldactone (Diuretic)
```  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
34
Topical dapsone | Aczone®
 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 ```
35
Topical azelaic acid | Finacea®
```  15% gel BID  Comedolytic and antibacterial. Does not promote resistance.  Can reduce hyperpigmentation  Adverse effects: ▪ Mildly irritating ```
36
Keloid Scarring
```  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)
37
maskne
```  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 ```