acne Flashcards
Pathogenesis ofAcne
New evidence 1 suggests
inflammation
precedes comedone
formation possibly2
- Sebum
production by the
sebaceous gland - Alteration in the
keratinization
process - C.acnes
follicular
colonization
1 or 4. Release of inflammatory mediators into the skin Acne is a cyclical process
Further Investigations
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
Recognizing the Chronicity of
Acne
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
AcneTreatment Algorithm
Comedonal: topical retinoid, BPO (no diff above 5%
more severe roal isotretinoin -> dont add oral agents to it
see slide 7
Retinoids
TOPICAL
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%
Retinoids
ORAL
Isotretinoin Accutane ▪ 10 mg, 20 mg, 40 mg Clarus Epuris
Acitretin-Etrenate (not
for acne, used for
psoriasis)
Soriatane
Retinoids
fxn
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
Mechanism ofAction of
Retinoids
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!
Fetal Risk Summaries and
Breast Feeding Compatibilities
typically say no to topical retinoid for pregnancy
evidence changing
A NoteAboutAcitretin
Acitretin (Soriatane®) and Etretinate
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
GeneralAdverse Effects for
Retinoids
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
Retinoids AE hypervitaminosis
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
Topical Retinoids-Mechanism
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
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
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
Topical Retinoids contra administration response time AE
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)
topical retinoids
Counseling points
• 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
Combination Formulations
remember active ingredients, not brand names
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!
Systemic Retinoid: Isotretinoin
mechanism
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
Systemic Retinoid: Isotretinoin
uses
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
Isotretinoin Contraindications
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
Isotretinoin
Dosing based on
weight
admin
response time
• 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
Isotretinoin: Low dose versus standard dosing
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.
Isotretinoin
Drug
interactions
• 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
iso monitroing
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
