treatment of acne-ii. important points to remember! self-treatment of acne is effective in patients...
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Treatment of Acne-II
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Important points to remember!
Self-treatment of acne is effective in patients mature enough to understand that acne can be controlled but not cured;
Treatment of noninflammatory acne: pharmacologic agents + nonpharmacologic measures;
Self treatment is appropriate only for grade I acne (i.e. noninflammatory acne of mild to moderate severity), presenting with open or closed comedones
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Classification of AcneGrade of Acne
Qualitative Description
Quantitative Description
IComedonal acneComedones only, < 10 on face, none on trunk, no scars, noninflammatory lesions only
IIPapular acne10-25 papules on face and trunk, mild scarring, inflammatory lesions < 5 mm in diameter
IIIPustular acneMore than 25 pustules, moderate scarring, size similar to papules but with visible purulent core
IVSevere persistent pustulocyctis acne
Nodules or cysts, extensive scarring, inflammatory lesions > 5 mm in diameter
-Recalcitrant severe cystic acne
Extensive nodules/cysts
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Exclusion for Self-Treatment
Grades II-IV acne: papules, pustules, nodules, cysts and/or scarring
Severe, recalcitrant acne (extensive nodules/cysts)
Exacerbating factors (e.g. comedogenic drugs)
Possible rosacea (If acne lesions persist beyond mid-20s or develop in the mid-20s or later, the symptoms may signal rosacea rather than acne vulgaris)
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Comedonal acne - topical treatment appropriate:
Pustular - an oral antibiotic would be best
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A) Before treatment:
Severe acne treated with Isotretinoin:
B) After 5 months
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Prescription Medication for acne:
Retinoic acid & DerivativesIsotretinoinAzelaic AcidAlpha-hydroxy acidsAntibiotics (topical or systemic)Hormonal therapy
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Retinoic Acid & Derivatives
Retinoic acid (tretinoin) is the acid form of vitamin A
13-cis-retinoic acid (isotretinoin) is analog of retinoic acid effective when given orally
Retinoic acid insoluble in water; susceptible to oxidation and ester formation particularly when exposed to light;
Topically applied retinoic acid remains chiefly in the epidermis (< 10% absorbed)
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Retinoic Acid & Derivatives
The small quantities absorbed following a topical application are metabolized by the liver and excreted in bile and urine;
Retinoic acid has several effects on epithelial tissues (lysosomes, PG-E2, cAMP, cGMP and RNA polymerase)
Action in acne: (1) decreased cohesion between epidermal cells (2) increased epidermal cell turnover.
This results in expulsion of open comedones and transformation of closed comedones into open ones
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Retinoic Acid & Derivatives Retinoic acid is applied initially in a concentration
sufficient to induce slight erythema with mild peeling
If too much irritaion is produced, decrease concentration or frequency of application;
During the first 4-6 weeks of therapy, comedones not previously evident may appear
However, with continued therapy, the lesions will clear, and in 8-12 weeks optimal clinical improvement should occur
(Retin-A Micro): timed release formulation with tretinoin containing microspheres. Less irritating
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Retinoic Acid & Derivatives
Prolonged use of tretinoin promotes :(1) dermal collagen synthesis(2) new blood vessel formation(3) thickening of the epidermisWhich helps diminish fine lines and wrinkles
Renova (0.05% cream): specially formulated for this purpose
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Retinoic Acid & Derivatives
The most common adverse effects (topical):
1. erythema, dryness: first few weeks of use, but resolve with continued therapy;
2. May increase tumerogenic potential of UV radiation (in animals). Thus, patients are advised to minimize or avoid sun exposure and use protective sunscreen
3. Allergic contact dermatitis: rare
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Adapalene (Differin)
A derivative of naphathoic acid that resembles retinoic acid in structure and effects
Applied 0.1% gel once dailyUnlike tretinoin:
1. photochemically stable2. less irritating
Most effective: mild to moderate acne vulgaris
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Treatment with Adpalene gel
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Tazarotene (Tazorac)
Acetylenic retinoid0.1% gelTreatment of mild to moderately severe
facial acneShould not be used by pregnant women
(pregnancy risk factor=X)Contraceptive counseling in women of
childbearing age.
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Isotretinoin (Accutane)
A synthetic retinoid currently restricted to the treatment of severe cystic acne that is recalcitrant to standard therapies;
MOA: (precise not known); inhibits sebaceous gland size and function
Well absorbed to circulation, extensively bound to plasma albumin,
elimination half-life of 10-20 hours
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Isotretinoin (Accutane)
Dose: 1-2 mg/kg, given orally in two divided doses
daily for 4-5 months; If severe cystic acne persists following this initial
treatment, a second course of therapy may be initiated after 2 months;
The skin would be sensitive during treatment. Patient is at high risk for abnormal healing and development of excessive gradulation following procedures (e.g. piercing, tatoos, epilation)
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• Isotretinoin is available in 10-, 20-, and 40-mg soft gelatin capsules for oral administration.
• Isotretinoin capsules should always be taken with food to maximize absorption
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Isotretinoin (Accutane)
Adverse EffectsCommon adverse effects (resemble hypervitaminosis A):
Dryness and itching of skin and mucous membranes
Less common: Headache, corneal opacities, pseudotumpr cerebri inflammatory bowel disease, anorexia, alopecia, muscle and joint pains
These effects are all reversible on discontinuation of therapy.
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Isotretinoin (Accutane)
Adverse Effects Skeletal hyperostosis has been observed in
patients receiving isotretinoin Premature closure of epiphyses noted in
children treated with this medication Lipid abnormalities (triglycerides, HDL) are
frequent Depression, psychosis, aggressiveness or violent
behavior & rarely suicidal thoughts (discontinuation MAY NOT be sufficient)
Teratogenecity
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Teratogenecity
the skull, ears, and eyes and include facial dysmorphia and cleft palate.
Internal abnormalities affecting the thymus gland, central nervous system, cardiovascular system, and parathyroid gland (hormone deficiency) are recognized.
In some cases, these abnormalities have resulted in fetal death.
Nursing mothers should not receive isotretinoin.
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Isotretinoin (Accutane)
Teratogenecity1. Women of childbearing age must use an
effective form of contraception for at least 1 month before; throughout isotretinoin therapy, and for one or more menstrual cycles following discontinuance of therapy
2. A serum pregnancy test must be obtained within 2 weeks before starting therapy
3. Therapy should be initiated only on the second or third day after the next normal menstrual period
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Isotretinoin (Accutane)
Monitoring parameters:1. CBC with differential & platelet count, baseline
sed. rate, glucose, 2. Pregnancy tests3. Lipids: prior to treatment & at weekly or
biweekly intervals until response to treatment is established
4. Liver function tests: prior to treatment & at weekly or biweekly intervals until response to treatment is established
5. Creatine Phosphokinase
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Azelaic Acid (Azelex)
Straight chain saturated dicarboxylic acid; effective in the treatment of acne vulgaris;
Its mechanism of action not fully determined. However, studies shown:
1. Antimicrobial activity against P acnes
2. In vitro inhibition of the conversion of testosterone to dihydrotestosterone
Initial therapy: once daily application of 20% cream to affected areas for 1 week. Then twice daily thereafter
Mild irritation with redness and dryness of the skin during the first week of treatment
Clinical improvement 6-8 weeks of continuous therapy
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Alpha-hyrdoxy Acids
They occur naturally in sugar cane, fruits and milk products;
The most useful AHAs in dermatologic practice are glycolic acid, lactic acid and gluconic acid
MOA: facilitate desquamation of the stratum corneum.
Effective in treatment of comedonal acne
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Topical Antibiotics
Commonly prescribed: erythromycin and clindamycin alone or in combination with benzoyl peroxide
MOA: (1) bactericidal activity against P acnes. (2) may also have anti-inflammatory effect
Topical antibiotics are not comedolytic, Bacterial resistance may develop to any of these
agents. The development of resistance is lessened if
topical antibiotics are used in combination with benzoyl peroxide
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Systemic Antibiotics
Tetracycline and congeners (minocycline and doxycycline)
Erythromycin, azithromycinTrimethoprim alone or in combination with
sulfamethoxazoleMOA: (1) P acnes; (2) Anti-inflammatory Minocycline is more effective than
tetracycline and bacteria has less resistance to this agent
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Systemic Antibiotics
Bacterial resistance to these agents may be reduced by combining them with topical retinoids and/or topical benzoyl peroxideMost common side effects:
phototoxicity from tetracycline group, especially doxycycline
Vertigo-like dizziness>> minocycline Stevens-Johnson syndrome>> trimethoprim-
sulfamethoxazole All oral antibiotics predispose to Candida
infections, particularly vaginitis
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Stevens Johnsons Syndrome
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Hormonal Therapy
MOA: estrogens are responsible for maintenance of the normal structure and function of the skin and blood vessels
Acne may be exacerbated by agents containing androgen-like progestins (e.g. norethindrone, lynestrenol, norethynodrel), whereas agents containing large amounts of estrogen usually cause marked improvement in acne
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ProgestinProgestational Activity(relative to 1 mg of
norethindrone)
Androgenic Activity(relative to 1 mg of
norethindrone)
norethindrone 1 mg1.01.0
norethrindrone acetate 1 mg1.21.6
ethynodiol diacetate 1 mg1.40.6
levonorgestrel 1 mg5.38.3
dl-norgestrel 1 mg2.64.2
norgestimate 1 mg1.31.9
norelgestromin 1 mg1.31.9
desogestrel 1 mg9.03.4
drospirenone 1 mg1.50.0
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Hormonal Therapy
FDA approved a triphasic, combination OCP:
Ortho-Tri-Cyclen: Ethinyl estradiol (0.035 mg) + Norgestimate:
Days 1-7 ………. 0.18 mg
Days 8-14……….0.215 mg
Days 15-21………0.25 mg
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Hormonal Therapy
A study showed that this OC reduced acne lesion counts by more than 50% in female subjects, compared with lesion reductions of about 26% in controls
Acne improvement during treatment with Ortho-Tri Cyclen may take 3-4 months to become apparent;
Main limitation of anti-androgen therapy for acne is that it cannot be used with male patients