Treatment of Acne-II

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

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

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)

Comedonal acne - topical treatment appropriate:

Pustular - an oral antibiotic would be best

A) Before treatment:

Severe acne treated with Isotretinoin:

B) After 5 months

Prescription Medication for acne:

Retinoic acid & DerivativesIsotretinoinAzelaic AcidAlpha-hydroxy acidsAntibiotics (topical or systemic)Hormonal therapy

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)

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

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

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

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

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

Treatment with Adpalene gel

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.

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

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)

• 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

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.

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

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.

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

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

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

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

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

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

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

Stevens Johnsons Syndrome

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

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

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

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