Acne is a highly prevalent disorder affecting many adolescents and adults.
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1 Treatment of Acne
2 Key Concepts Acne is a highly prevalent disorder affecting many adolescents and adults. It is an extremely complex disease with an etiology originating from multiple causative and contributory factors. Elements of pathogenesis involve defects in epidermal keratinization, androgen secretion, sebaceous function, bacterial growth, inflammation, and immunity. Acne vulgaris cannot be "cured." Goals of treatment of this chronic disorder include control and alleviation of symptoms by reducing the number and severity of lesions, slowing progression, and limiting disease duration and recurrence. Key elements for patient adherence to therapy include prevention of long-term disfigurement associated with scarring and hyperpigmentation and avoidance of psychologic suffering. The most critical target for treatment is the microcomedone, as the entire pathogenic cascade of acne is arrested if follicular occlusion is minimized or reversed. This involves a combination of treatment measures, integrating pharmacologic protocols targeting all four mechanisms involved in acne pathogenesis: increased follicular keratinization, increased sebum production, bacterial lipolysis of sebum triglycerides to free fatty acids, and inflammation.
3 Nondrug measures are aimed at both long-term prevention and treatment. Patients should eliminate aggravating factors, maintain a balanced, low-glycemic load diet, and control stress. They should wash twice daily with a mild soap or soapless cleanser, and restrict cosmetic use to oil-free products. Comedone extraction results in immediate cosmetic improvement in about 10% of patients. Shaving should be done as lightly and infrequently as possible, using a sharp blade or electric razor. First-, second-, and third-line therapies should be selected and altered as appropriate for the severity and staging of the clinical presentation. Treatment is directed at controlling the disorder, not curing it. Regimens should be tapered over time, adjusting to response. The smallest number of agents should be used at the lowest possible dosages to ensure efficacy, safety, avoidance of resistance, and patient adherence. Once control is achieved, simplify the regimen but continue with some suppressive therapy. It takes 8 weeks for a microcomedone to mature; thus, any therapy must be continued beyond this duration to assess efficacy in terms of comedonal and inflammatory lesion count, control or progression of severity, and management of associated anxiety or depression. Safety endpoints include monitoring for adverse effects of treatment. Through empathic and informative counseling, the health professional can motivate the patient to continue long-term therapy.
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7 To assess severity grading, several taxonomies are used but none are accepted universally. The following system includes factors such as lesion type, location of lesions, and number and status of irreversible sequelae: Type 1: Comedones only, fewer than 10 lesions on the face, no lesions on the trunk, and no scarring. Type 2: Papules, lesions on the face and trunk, mild scarring Type 3: Pustules, more than 25 lesions, moderate scarring Type 4: Nodules or cysts, extensive scarring
8 Nodules Papules Pustules
9 Papule pimple whiteheads pustule blackheads
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15 Oral Contraceptives. Estrogen-containing contraceptive agents have been studied for the treatment of acne. Those currently approved by the US Food and Drug Administration (FDA) for the management of acne contain norgestimate with ethinyl estradiol and norethindrone acetate with ethinyl estradiol. There is good evidence and consensus opinion that other estrogen-containing oral contraceptives are also equally effective. 44 The effect on acne of other estrogen-containing contraceptives (e.g., transdermal patches, vaginal rings) has not been studied.
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17 Classification of Acne Grade of Acne Qualitative Description Quantitative Description I Comedonal acne Comedones only, < 10 on face, none on trunk, no scars, noninflammatory lesions only II Papular acne papules on face and trunk, mild scarring, inflammatory lesions < 5 mm in diameter III Pustular acne More than 25 pustules, moderate scarring, size similar to papules but with visible purulent core IV Severe persistent pustulocyctis acne - Recalcitrant severe cystic acne Nodules or cysts, extensive scarring, inflammatory lesions > 5 mm in diameter Extensive nodules/cysts
18 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)
19 Comedonal acne - topical treatment appropriate: Pustular - an oral antibiotic would be best:
20 Severe acne treated with Isotretinoin: A) Before treatment: B) After 5 months
21 Treatment of Acne Non-pharmacologic therapy Cleansing of Skin Minimize Exacerbating factors Pharmacologic Therapy
22 Pharmacologic Therapy Benzoyl Peroxide Salicylic acid Sulfur Sulfur-Resorcinol combination products Alpha-hydroxy acids
23 Benzoyl Peroxide Available in variety of concentrations (2.5%, 5% and 10%) and dosage forms (lotions, gels, creams, cleansers, masks and soaps); MOA: (1) irritation & desquamationprevents closure of pilosebaceous duct. Increase turnover rate of epithelial cells. (2) Oxidizing potential-antibacterial activity, decreasing P.acnes Safety studies are ongoing
24 Benzoyl Peroxide The most effective and widely used OTC drug for non-inflammatory acne; Clinical response to all concentrations is similar in reducing the number of inflammatory lesions Different formulations are not equivalent: alcohol gel is superior to lotion of the same concentration; Washes and cleansers: have little or no comedolytic effect
25 Benzoyl Peroxide Adverse Effects: excessive dryness, peeling, some skin sloughing, erythema or edema lower concentrations must be used for shorter duration Stinging/burning: non alarming unless persist or worsen Precautions: (1) bleach hair, clothes, bed linens, (2)avoid excessive sun or sunlamps, (3) alcohol-based products (e.g. after shave lotion)( may exacerbate stinging/burning
26 Salicylic Acid Available in wide range: 0.5%-2% A milder, less effective alternative for teretoin MOA: acts as a surface keratolytic, mild comedolytic agent When used in cleansing preparations: adjunctive treatment
27 Sulfur Keratolytic and antibacterial (precipitated or colloidal) 3%-10% Generally: accepted as effective in promoting the resolution of existing comedones, but, on continued use, may have a comedogenic effect Alternative forms of sulfur: Na thiosulfate, Zn sulfate, Zn sulfide NGRSE Applied in thin film to skin 3 times daily Have noticeable color and odor
28 Sulfur-Resorcinol combination 3-8% sulfur with resorcinol 2% (enhances the effect of sulfur) MOA: keratolytics, fostering cell turnover and desquamation Resorcinol produces a reversible dark brown scale on some darker-skinned individuals
29 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
30 Therapeutic Comparison Benzoyl Peroxide Salicylic Acid Sulfur Bactericidal Yes - - Keratolytic - Yes Yes Comedolytic - Yes Yes Concentration 2.5%-20% 0.5%-2% 2%-10% Frequency of use 1-2 times daily Adverse effects Bleached hair and clothing Used mainly as cleanser, then rinsed off Potent keratolytic at high concentration 1-3 times daily Color, unpleasant odor
31 Product Selection Guidelines Cosmetic appearance may influence compliance Cleansers (bars, liquids, suspensions, lotions, creams, gels, and pads/wipes) are not of much value (WHY?) Lotions & creams with low fat content are intended to counteract drying (astringent effect) and peeling (keratolytic effect): alternative to more effective gels for dry sensitive skin or during winter weather
32 Patient Education: The goal of self-treatment is to control mild acne, thus preventing more serious form from developing Acne usually goes away on its own Symptoms can usually be managed with diligent and long term treatment Best approach is use cleansers and medications to keep skin ducts and orifices open
33 Patient Education: Cleanse skin thoroughly but gently at least twice daily to produce a mild drying effect that loosens comedones, using soft wash cloth, warm water and facial soap without moisturizing oils To prevent or minimize acne flare-ups, avoid or reduce exposure to environmental factors, such as dirt, dust, petroleum products, cooking oils or chemical irritants
34 Patient Education: To prevent friction or irritation that may cause acne flare-ups, do not wear tightfitting clothes, headbands, or helmets, avoid resting the chin on the hand; To minimise acne related to cosmetic use, do not use oil based cosmetics and shampoos
35 Patient Education: To prevent excessive hydration of the skin, which can cause flare-ups, avoid areas of high humidity and do not wear tight fitting clothes that restrict air movement; Try to maintain proper diet, although a link between diet and acne is not found; Avoid stressful situations. Stress may play a role in acne flare-ups but it does not cause acne
36 Prescription Medication for acne: Retinoic acid & Derivatives Isotretinoin Azelaic Acid Antibiotics (topical or systemic) Hormonal therapy
37 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)
38 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
39 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
40 Retinoic Acid & Derivatives Prolonged use of tretinoin promotes : (1) dermal collagen synthesis (2) new blood vessel formation (3) thickening of the epidermis Which helps diminish fine lines and wrinkles Renova (0.05% cream): specially formulated for this purpose
41 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
42 Adapalene (Differin) A derivative of naphathoic acid that resembles retinoic acid in structure and effects Applied 0.1% gel once daily Unlike tretinoin: 1. photochemically stable 2. less irritating Most effective: mild to moderate acne vulgaris
43 Treatment with Adpalene gel
44 Tazarotene (Tazorac) Acetylenic retinoid 0.1% gel Treatment of mild to moderately severe facial acne Should not be used by pregnant women (pregnancy risk factor=x) Contraceptive counseling in women of childbearing age.
45 Isotretinoin (Accutane) A synthetic retinoid currently restricted to the treatment of severe cystic acne that is recalcitrant to standard therapies; Well absorbed to circulation, extensively bound to plasma albumin, elimination half-life of 21 hrs (parent drug), hrs (metabolite) MOA: inhibits sebaceous gland size and function.details
46 MOA- isotretenoin: Isotretinoin prevents the formation of new comedos and resultant inflammatory lesions by decreasing the size and secretions of the sebaceous glands, normalizing follicular keratinization, and exerting anti-inflammatory effects. Sebum production is reduced by at least 90% through competitive inhibition of retinol dehydrogenase-4, the enzyme that mediates the skin's production of dihydrotestosterone and androstenedione.
47 Isotretinoin (Accutane) Dose: mg/kg/day, 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 granulation following procedures (e.g. piercing, tatoos, epilation)
48 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
49 Isotretinoin (Accutane) Adverse Effects Common 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.
50 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
51 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.
52 Facial dysmorphism
53 Cleft palate
54 Isotretinoin (Accutane) Teratogenecity 1. 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
55 Isotretinoin (Accutane) Monitoring parameters: 1. CBC with differential & platelet count, baseline sed. rate, glucose, 2. Pregnancy tests 3. 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 6. Blood Glucose
56 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
57 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
58 Systemic Antibiotics Tetracycline and congeners (minocycline and doxycycline) Erythromycin, azithromycin Trimethoprim alone or in combination with sulfamethoxazole MOA: (1) P acnes; (2) Anti-inflammatory Minocycline is more effective than tetracycline and bacteria has less resistance to this agent
59 Systemic Antibiotics Bacterial resistance to these agents may be reduced by combining them with topical retinoids and/or topical benzoyl peroxide Most common side effects: phototoxicity from tetracycline group, especially doxycycline Vertigo-like dizziness>> minocycline Stevens-Johnson syndrome>> trimethoprimsulfamethoxazole All oral antibiotics predispose to Candida infections, particularly vaginitis
60 Stevens Johnsons Syndrome
61 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
62 Progestin Progestational Activity (relative to 1 mg of norethindrone) Androgenic Activity (relative to 1 mg of norethindrone) norethindrone 1 mg norethrindrone acetate 1 mg ethynodiol diacetate 1 mg levonorgestrel 1 mg dl-norgestrel 1 mg norgestimate 1 mg norelgestromin 1 mg desogestrel 1 mg drospirenone 1 mg
63 Hormonal Therapy FDA approved a triphasic, combination OCP: Ortho-Tri-Cyclen: Ethinyl estradiol (0.035 mg) + Norgestimate: Days mg Days mg Days mg
64 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
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