Acne Vulgaris (2) Flashcards
Acne is more common in which patients?
Adolescents (effects 85% of teens)
-tends to occur younger in girls
note - can persist beyond adolescence or have late onset (>25 years old)
Sebum
Oily secretion produced by the sebaceous gland
Keeps skin and hair hydrated
Follicle
small pore/cavity in skin that surrounds the root of a hair
(where the hair grows)
Comedome
Clogged hair follicle - filled with skin, bacteria, and sebum
(note - some therapies are “comedolytic” - meaning they inhibit the formation of comedomes)
Keratinocytes and Hyperkeratinization
main skin cells found on the surface of skin (epidermis)
have a fast turnover rate
Hyperkeratinization (overproduction of skin cells) - there is overproduction of the keratinocyte layer, or failure to slough off as a normal - resulting in thickening of the layer
-this is a sign of acne
Keratinolytic agents can be used to remove/lyse keratinocytes
Etiology of acne (4)
There are 4 parts that contribute to etiology …
- Increased sebum production
- Inflammation
- Bacterial colonization (with gram positive Cutibacterium acnes)
- follicular hyperkeratinozation (overproduction of skin cells, increase clogging)
Types of acne lesions
Present differently based on if inflammation is occurring or not…
Non-inflammatory:
First starts as microcomedomes (small clogged hair follicles, not visible at first)
Then forms closed comedomes (white heads)
Which can progress to open comedomes (black heads)
Inflammatory
Development of papules and pustules
-papules don’t have puss, pustules do
And can progress to even more severe… nodules and cysts
-nodules don’t have puss and cysts do
-these are deeper lesions and can cause scarring
Risk factors for acne
Biggest one: Hormonal changes
-typical onset is during puberty/pre puberty
-also occur with pregnancy
-hormone altering medications
Genetic factors - first degree relatives
Possibly - diet (this is controversial)
-excessive milk consumption
-high glycemic load
What are some factors that can exacerbate acne?
Oil based cosmetics
Scratching, picking, scrubbing (increases lesion exposure to bacteria)
Tight/occlusive clothing, helmets, headbands (local irritation and friction)
Constant exposure to dirt, oil, and chemicals (occupational)
Certain medications
Certain medical conditions (hormone induced acne -pregnancy, premenstrual flares)
Extreme stress or anger
Which medications can induce acne?
Corticosteroids
Anabolic steroids
Isoniazid
Lithium
Phenytoin
What are some complications of acne? (3)
Depression
Anxiety
Scarring
What are some exclusions to self care?
- Moderate, severe, or cystic acne
- concurrent use of comedogenic medications (e.g. corticosteroids, isoniazid, lithium, phenytoin)
- Unavoidable mechanical irritation (such as occupational factors)
- Probable that the patient has another form of acne (e.g. rosacea)
Non pharm strategies
Eliminate exacerbating factors (environmental, behavioral, and emotional factors)
Proper skin care
-cleanse no more than twice daily (frequent cleansing can cause dry skin and worsening of acne)
-use mild soap or non-soap cleanse (harsh soaps have alkaline pH which can promote C. acne growth)
-avoid abrasive products (e.g. exfoliants, harsh washcloths)
-hydrate skin with moisturizer once daily
Almost all topical acne agents cause what side effect?
Xeroderma - dry skin
(at least when initiating therapy, can resolve with time)
Benzoyl Peroxide MOA
Exhibits bactericidal effects against C. acne
Once it is absorbed by the skin, it is metabolized to benzoic acid
Benzoic acid is then metabolized by cysteine in the skin, releasing free-radical oxygen species resulting in oxidation of bacterial proteins
Benzoyl peroxide counseling points
-Available OTC
-Use lowest strength once daily to small affected areas for the first 3 days to test tolerance, then slowly increase to 3 times a day
-decrease frequency if irritation and skin peeling occurs (note mild erythema and scaling usually subsides after 1-2 weeks of use)
-avoid contact with hair and clothes (can bleach)
-use sunscreen and avoid sun exposure to decrease risk of photosensitivity
-visible improvements may occur from 5 days to 3 weeks, but full effect may take 8-12 weeks and adherence is important for this to occur
Retinoid MOA
These are derived from vitamin A
When topically applied, they remain in the epidermis (minimal systemic absorption)
They bind specific receptors in cells - retinoic acid receptors (RARs) and retinoid X receptors (RXRs)
-these receptors are involved in regulating gene expression and cell differentiation
(so their MOA is kind of like steroids - bind to nuclear receptors which then move to nucleus and alter gene transcription)
They decrease cohesion between epidermal cells and increase epidermal cell turnover causing the expulsion of open comedomes and the conversion of closed into open ones
(Animal studies suggest that this may be tumorigenic)
What are the available topical retinoid products (3)
Adapalene (Differin) - available OTIC
Tretinoin (Retin-A, Tretin-X) - prescription only
Tazarotene (Tazorac) - prescription only
Note - there is no evidence to suggest that one works better than the other
Topical retinoids counseling points
Apply thin layer to affected skin once daily at bedtime
Can cause dry skin, scaling, erythema, skin irritation during the first few weeks of use (decrease frequency if side effects aren’t tolerable)
-peeling and dryness is expected, this is how these drugs work to open microcomedones
-note acne may look like its worsening at first (since opening of microcomedones occurs)
Can cause photosensitivity (use sunscreen, avoid exposure)
Do NOT use in pregnancy (due to risk of systemic absorption)
May take 8-12 weeks to see full therapeutic effect
Avoid applying tretinoin at the same time as __________
Benzoyl peroxide
-tretinoin can be oxidized and inactivated by benzoyl peroxide (this does not apply to the other retinoids)
Alpha Hydroxy Acids (AHA) considerations/use
E.g. lactic, glycolic, and citric acids
These are available OTC, are referred to as “chemical peels”
Not as effective as other available agents, not in the guidelines
May quicken the process of non-inflammatory comedone resolution, but the improvement is usually mild and temporary
Should only be used sparingly (every 2 weeks)
Salicylic acid MOA
This is a lipophilic acid
It works by dissolving intercellular cement (the substance that causes skin cells to stick together) - preventing pores from clogging up
Makes it easier to shed skin cells
Also has some anti-inflammatory properties
Sulfur MOA
keratolytic, antiseptic, antiparasitic, and antiseborrheic
Exerts keratolytic effect by reacting with cysteine within keratinocytes - producing cystine and hydrogen sulfide (H2S)
H2S breaks down keratin
BHA (salicylic acid) counseling points
Available OTC
Should be applied 1-3 times daily only to the affected area
-application to large areas can cause systemic toxicity
-so, should only be used as spot therapy or as wash off formulations
Can cause skin peeling/dryness (decrease frequency if cannot tolerate)
Do NOT use in patients with aspirin allergy
Not preferred option - less effective than benzoyl peroxide
Azelaic Acid MOA
Naturally occurring dicarboxylic acid
AZA is metabolized via beta oxidation pathway to form malonyl-CoA or acetyl CoA
Has antibacterial, comedolytic and peeling action
Exact mechanism is unknown but inhibits the synthesis of cellular proteins in anaerobic and aerobic bacteria
Also has anti-inflammatory properties
What are the 2 azelaic acid products available
Azelex (cream)
Finacea (gel/foam)
Prescription only for both
Azelaic acid counseling points
Apply twice daily (morning and evening)
Mostly localized ADRs - burning, tingling, stinging of skin (decrease frequency if not tolerated)
Can cause hypopigmentation in darker skinned people
Do not use occlusive dressing/wrapping after application to avoid systemic absorption
What are 3 topical antibiotics that can be used for acne vulgaris?
- Dapsone gel
- Clindamycin gel
- Erythromycin gel
Clindamycin is preferred
(erythromycin is not as effective compared to clindamycin due to resistance)
Note - clindamycin and erythromycin also come as combination products with benzoyl peroxide
Dapsone MOA
interfered with folate synthesis
Dapsone clinical considerations
Has anti-inflammatory effect (other topical antibiotics do not)
If more effective in females than males
Can cause orange skin discoloration if used with benzoyl peroxide
Clindamycin and erythromycin MOA
Clindamycin is a lincosamide
Erythromycin is a macrolide
Both inhibit bacterial protein synthesis by binding to the 50S subunit of the ribosome
Which oral antibiotics can be used for acne vulgaris? Which are preferred?
Tetracyclines
-Doxycycline
-tetracycline
-minocycline
Macrolides
-erythromycin
-azithromycin
Tetracyclines are preferred over macrolides for acne
And doxycycline is the preferred out of the tetracyclines
Macrolides are used off label if tetracyclines can not be used and patient needs systemic antibiotic
When should oral antibiotics be used for acne?
Reserved for moderate/severe cases of acne vulgaris
And they should NEVER be used as monotherapy for acne (combine with benzoyl peroxide and retinoid) - to reduce antibiotic resistance
Tetracycline should not be used in which patients? (2)
Children under 8
Pregnant women
Tetracycline counseling points
Common ADRs: stomach upset, nausea, photosensitivity, headache, diarrhea
To avoid stomach upset take with food and water
Tetracycline chelate cations … consider DDIs - separate from calcium, aluminum, magnesium, and iron
Tetracyclines should be avoided with concomitant use of which 3 medications
Oral retinoids
Methotrexate
Acitretin
Macrolide counseling points
Main ADRs: GI upset (n/v/d), headache
They are strong CYP3A4 inhibitors
-more interactions with erythromycin than azithromycin
-erythromycin is contraindicated with lovastatin and simvastatin
Chelate ions … separate administration from antacids or calcium, magnesium, aluminum containing medications
Isotretinoin MOA
Synthetic retinoid
Exact mechanism is unknown - appears to act by inhibiting sebaceous gland size and functioning
When isotretinoin used
Reserved last line for severe, refractory, cystic acne
-because of many side effects
Available isotretinoin products
Brands: Acutane, Clavaris, Asorbica, Amnesteem
(10-40 mg capsules)
Isotretinoin dosing
Weight based dosing, start low to minimize reactions…
start at 0.5 mg/kg/day and divide into 2 daily doses
-do this for 1 month
Then increase to full dose - 1 mg/kg/day (as tolerated)
How long should isotretinoin be used for?
15-20 weeks or until full clearance of acne cysts
Isotretinoin counseling points
Take with food for better absorption
Teratogenic - BBW for birth defects
-requires REMS program - iPLEDGE to prevent fetal exposure
Common side effects of isotretinoin and management of them (3)
-Dry skin, lips, nose, eyes, and mouth
^use moisturizer, lip balm regularly
-Photosensitivity
^avoid sun exposure, use sunscreen (SPF >15) daily
-Back/muscle pain
^monitor MSK pain tolerability
Rare but serious side effects of isotretinoin and management of them
-Depression, suicidal ideation, psychosis
^monitor and discontinue if psychiatric symptoms occur
-Conjunctivitis or eyelid inflammation
^monitor for vision changes
-Acute pancreatitis
^avoid alcohol, monitor for increased triglycerides
-Inflammatory bowel disease
^monitor and discontinue if severe diarrhea, abdominal pain, or rectal bleeding occurs
-Hepatitis
^monitor for increased liver enzyme tests
-Neutropenia
^monitor for decreased WBC count
Oral and topical antibiotics for acne should never be used as _________________
Monotherapy!
They should be used with topical products to avoid antibiotic resistance
Comparison of topical vehicle formulations
Bars and liquids - less effective because washed off, but better tolerated because not absorbed
Gels and solutions - work as astringents (drying effect) - most effective for acne
Creams and lotions - add hydration to skin, good for dry skin but can clog pores
Ointments - clogs pores not good for acne
Oral and topical antibiotics should only be used for how long?
8-12 weeks (3-4 months)
Sarecycline
(Seysara)
This is new tetracycline that has only been approved for the treatment of moderate/severe acne
It has weight based dosing
Can be taken with or without food (with food to help stomach upset)
But should be taken with a full glass of water - to prevent esophageal irritation and ulceration
(same contraindications/drug interactions as other tetracyclines)
Mild acne treatment algorithm
For mild non-inflammatory acne (comedones only)
-First line - monotherapy topical retinoid
-Alternative: BP or azelaic acid
For mild inflammatory acne (papules/pustules)
-First line - topical retinoid + benzoyl peroxide
-alternative: TR or BP or azelaic acid
Note - alternatives can be used if inadequate response to first line or if unable to use first line
-can switch or add agents…
If partial response after 12 weeks add another topical agent
If no response after 12 weeks switch to another topical agent
Moderate acne treatment algorithm
For inflammatory papules/pustules
-First line: topical retinoid + benzoyl peroxide
Alternative: consider addition of topical antibiotic
If inflammatory + nodules are present:
-First line: topical retinoid + benzoyl peroxide + oral antibiotic
-Aternative: consider addition of COC or spironolactone
Severe acne treatment algorithm
If inflammatory + nodules:
First line: topical retinoid + benzoyl peroxide + oral antibiotic
Alternative: consider addition of COC, spironolactone, can consider isotretinoin
If inflammatory + cysts
First line: oral isotretinoin
Alternative: consider addition of COC, spironolactone, and oral antibiotic + BP
How long should acne therapy be used for?
Typically 12 weeks - after that we start to taper down to monotherapy if possible
At which point can we consider efficacy monitoring?
No sooner than 8 weeks - much longer for some things/full efficacy
-just know and counsel patients that it will take a while to see improvement and adherence is important to get to that point
What are 3 alternative agents that can be used for acne treatment
- Combined oral contraceptives (COC)
- Spironolactone
- Clascoterone
Combined oral contraceptives for acne
Work be decreasing androgen production and binding free circulating testosterone
Can only be used in women who also want contraceptive therapy
Can only be used in females
Cannot be used in pregnancy
Takes 6 cycles of COC therapy (6 months) for full effect
More adverse effects and discontinuation as a result
COCs should NOT be used in which cases?
-Pregnancy or breastfeeding
-35 or older and heavy smoker
-Uncontrolled hypertension
-History of blood clots or stroke
-History of migraine
-Current breast cancer
-Current liver disease or liver tumor
Spironolactone for acne
Works by decreasing testosterones production
Not FDA approved for acne
Can only be used in females
Should NOT be used in pregnancy
ADRs: gynecomastia, hyperkalemia, hypotension, diuresis
Clascoterone
Androgen receptor inhibitor
Topical application
Can be used for males or females - can be used if failed initial topical therapy or in a combination regimen
ADRs - xeroderma, peeling
Oral corticosteroids for acne
Not generally recommended or used
May be used in severe exacerbations to quickly decrease inflammation
