Acne Vulgaris Lecture 1 PDF

Dermatologic Disorders Acne Vulgaris ACNE Guidelines: https://www.aad.org/member/clinical-quality/guidelines/acne Introduction  Introduction - It is essential for pharmacists to be able to: Recognize and differentiate common skin con...

Dermatologic Disorders Acne Vulgaris ACNE Guidelines: https://www.aad.org/member/clinical-quality/guidelines/acne Introduction  Introduction - It is essential for pharmacists to be able to: Recognize and differentiate common skin conditions, Suggest appropriate treatments for these conditions, Know when to refer patients to a primary care provider or dermatologist for further evaluation.  Introduction…cont’d Human Skin and Principles of Topical Therapy The skin is the largest organ of the human body, accounting for approximately 15% of the body weight of an average person. Skin performs a number of vital physiologic functions, including: - Protecting the body from injury. - Serving as a barrier against microorganisms. - Synthesizing melanin to protect underlying tissues from irradiation. - Receiving sensory input from the proximal environment. - Producing cholecalciferol (vitamin D3) through exposure to ultraviolet (UV) radiation. The skin also plays a major role in thermoregulation, as both cutaneous blood flow and perspiration contribute to maintaining a normal core body temperature. Cross-Section of Human Skin  Introduction Introduction…cont’d …cont’d Human skin Human skin is about 1 to 2 mm thick. It is composed of three functionally distinct regions: epidermis, dermis, and hypodermis. The epidermis—the outermost and thinnest layer of the skin—regulates the water content of the skin and controls drug absorption into the lower layers and systemic circulation. The dermis, immediately below the epidermis, is much thicker than the epidermis and contains nerve endings, blood vessels, and hair follicles. It also contains the sebaceous glands, which produce oil (sebum) that lubricates the skin and prevents excess drying. The hypodermis provides nourishment and cushioning for the upper two layers.  Introduction Introduction…cont’d …cont’d Principles of Drug Absorption Drugs used to treat dermatologic disorders may be formulated as ointments, creams, lotions, gels, solutions, suspensions, aerosols, foams, powders, or pastes. When a drug is applied topically, it is transported from the skin surface to the general circulation through percutaneous absorption. The major mechanism of drug absorption is passive diffusion through the stratum corneum (SC) —the outermost layer of the epidermis—followed by transport through the deeper epidermal regions and then the dermis. The SC provides the greatest resistance and is often a rate-limiting barrier to percutaneous absorption.  Product Selection Considerations A general approach to product selection for dermatologic disorders is summarized by the adage: “If it’s dry, wet it; if it’s wet, dry it” Dry lesions benefit from products that have enough occlusive property to help the skin surface retain water content. Ointments are the vehicle of choice for dry lesions, especially areas of skin that are very dry and fissured. Ointments should not be used on: - lesions that are moist, weeping, oozing, or infected. - Puncture wounds or lacerations; intertriginous areas (e.g., axillae, skin folds of the groin, finger and toe webs), mucous membranes, and acne-prone areas. Ointments with oleaginous hydrocarbon bases such as petrolatum are transiently occlusive, promote hydration, and generally enhance the transport of medications through the skin layers.  Product Selection Considerations …….continued Wet lesions benefit from products with a higher water content; these products provide a drying effect as water evaporates from the skin. Creams may be used for dry lesions. Creams should be used on lesions that are moist, macerated, weeping, or oozing. Compared with ointments, creams : - Allow fluid to flow freely from lesions - Do not trap bacteria. However, solutions, gels, or lotions are the vehicles of choice for wet areas.  Product Selection Considerations…….continued Pharmacists should consider patient preference when recommending products for dermatologic disorders. Ointments typically are very greasy; as a result, they can be difficult for patients to spread and remove and may stain clothing and other fabrics. To avoid a greasy feeling, patients should be advised to: - warm an ointment product gently in the hands, - apply a very thin layer, and - massage it into the skin gently but thoroughly. Creams generally are a more acceptable alternative for patients who are unwilling to use ointments. Foams, sprays, and lotions are especially useful in areas that pose application challenges such as the scalp, other hairy areas, and locations that are difficult to reach. ACNE Vulgaris  Definition It is a chronic inflammatory dermatosis notable for open or closed comedones (blackheads and whiteheads) and inflammatory lesions, including papules, pustules, or nodules (also known as cysts).  Prevalence/incidence http://bbi.com.eg/Viewer/ProductImages/15121409111783.jpg Acne vulgaris is the most common skin condition in the United States, affecting an estimated 40 million to 50 million people. Although roughly 85% of people with acne are adolescents, acne can occur at any age. – 16-18 year olds: >90% – 10-12 year olds: 40% of girls; 15% of boys – Peak severity: 13 for girls; 15 for boys – Severity and extent reduce after adolescence (settles in 80% by 18-19, 95% by 25) but most experience occasional lesions into adulthood Upward of 40% of men and women older than 25 years of age have acne.  Pathophysiology Acne is the result of several pathologic processes that occur with the pilosebaceous unit located in the dermis. It is the site of acne disorder. It consists of: ✓ Hair follicle: a tubular infolding (Invaginaiton) of the epidermis containing the root of hair. ✓ Sebaceous gland (secretes sebum): Sebum is a light yellow, oily fluid responsible for keeping skin & hair moisturized. ✓ Arrector pili muscle: Is involuntary muscle responsible for hair erection when it contracts in case of cold and fear.  Pathophysiology …..continued Acne progresses through four pathogenic stages: (1) Androgenic hormonal triggers and Increased follicular keratinization. (2) Increased sebum production. (3) Proliferation of the gram +ve bacteria Propionibacterium acnes with bacterial lipolysis of sebum triglycerides to free fatty acids. (4) Inflammation.  Pathophysiology …..continued During puberty, there is increase in the secretion of these hormones and subsequently, the sebaceous glands enlarge in size, become active and start secreting oil rich sebum. There is increased keratinization of epidermal cells and development of an obstructed sebaceous follicle, called a microcomedone (sign of acne), the initial pathologic lesion.  Pathophysiology …..continued Cell debris adhere to each other, forming a dense keratinous plug. Propionibacterium acnes (P. acnes), an anaerobic organism, is also found in the normal flora of the skin. This bacteria proliferates in the mixture of sebum and keratinocytes and can result in an inflammatory response.  Pathophysiology …..continued The action of P. acnes is mainly two folds: 1. It generates enzymes like lipases which digest the triglycerides in the sebum into free fatty acids which irritate the area 2. Release certain chemotactic agents which attract the inflammatory cells like neutrophils to arrive at the site. This further results in the keratin structure of the hair follicle which become plugged and blocked.  Pathophysiology …..continued The degree of plugging and inflammation decides the severity of acne (Stages of Acne): When this keratin plug blocks the hair follicle opening on the surface, it is known as a closed comedone (white head). An open comedone (blackhead) occurs when the orifice is open and the sebum comes in contact with the atmosphere and changes its color into a black plug.  Pathophysiology …..continued The dark color of open comedones is attributable to the presence of melanin and oxidation of lipids upon exposure to air; blackheads are not caused by dirt, nor are they an indicator of poor hygiene. When the inflammation and infection is severe, the follicular wall ruptures, releasing part of the comedone into the dermis, thus causing intense foreign body reaction and inflammation in the dermis. This results in pustules, cysts and nodules.  Development of acne keratinocytes form a plug that blocks the follicular opening Comedo (pharmacist) Inflammatory acne (physician) White head or closed Black head Papule/nodule Pustule/cyst comedo or opened comedo 25 Stages of ACNE  Clinical Presentation Closed and open comedones constitute noninflammatory acne. These lesions often are the first to manifest in the early stage of puberty and often appear initially on the forehead. With the progression of puberty and with age, lesions tend to appear on areas of the body below the neck (e.g., the chest and back).  Clinical Presentation ………continued Closed and open comedones are the precursors of inflammatory acne lesions, which result from proliferation of P. acnes and localized tissue destruction. Acne papules are characterized by redness and inflammation in and around the follicular canal  Clinical Presentation ………continued Inflammatory acne lesions (Papule) - It is a solid, raised redden inflammatory lesion on the surface of the skin. - The content of the follicular duct ↑ and can be easily ruptured and then all contents may be get out to the surface of skin which are sebum, dead cells and propionibacterium bacteria which feeds on the sebum. - Papules occur along with comedones on the face and give a sand paper like feel.  Clinical Presentation ………continued Inflammatory acne lesions (Pustules) have visible purulence in the center of the lesion. They are raised redden inflammatory lesions filled with pus, which may rupture spontaneously.  Clinical Presentation ………continued Inflammatory acne lesions (Nodules) Nodules form when the follicular wall ruptures and releases the contents of the follicle into the surrounding dermis. It is most severe inflammatory acne. It resembles the papule in structure but this causes scarring as it extends into the deep layers of the skin. It can cause tissue destruction leading to scarring and it might not respond to skin therapies as well  Risk Factors A. Puberty B. Ultraviolet light may make sebum more comedogenic, but some of the visible wavelengths may reduce the follicular bacterial population. C. Diet: lower-milk-intake and lower-glycemic-load diets have potential benefits in acne. C. Family history and increased body mass index increased the risk for acne D. Worsening of acne has been associated with times of increased stress.  Non-pharmacologic Measures Proper skin hygiene including: Washing of affected area twice daily with mild or medicated soap followed by gentle drying. N.B. - Overcleansing or using abrasive products may worsen acne. - Medicated cleansing products (bars or liquids) generally do not leave enough active ingredient on the skin to be effective. Patients should use water based cosmetic products and wash oily hair frequently with a water-based shampoo. Avoidance of facial masks and scrubs. Picking, pinching and squeezing of acne lesions must be avoided Exacerbating factors especially chocolate, cola, fried foods, or milk products which are considered to increase the acne development must be identified and avoided.  Non-pharmacologic Measures……continued Minimizing factors that exacerbate acne can help control the condition: - Local irritation or friction from occlusive clothing, headbands, helmets, friction producing devices (acne mechanica). - Exposure to dirt, vaporized cooking oils, or certain industrial chemicals such as coal tar and petroleum derivatives may cause (occupational acne). - Oil-based cosmetics and topical products that contain comedogenic oils (e.g., lanolin, mineral oil, cocoa butter) may exacerbate acne or even induce it. - Certain medications can exacerbate preexisting acne. Such as; phenytoin, isoniazid, moisturizers, phenobarbital, lithium, ethionamide, and steroids. However, patients should not discontinue any prescribed medication without consulting the prescriber.  Non-pharmacologic Measures Dermatologists may use procedures such as surgical comedo extraction, chemical peels, and microdermabrasion as adjunct therapy to improve cosmetic appearance. Acne scarring is treated with various microsurgical techniques such as dermabrasion, laser therapy, chemical peels, and tissue augmentation.  Treatment Selection by Acne Type Type Treatment Options Comedonal acne Topical retinoid, azelaic acid Or Salicylic acid (as alternative or add-on) Maculopapular acne Topical retinoid + topical antimicrobial (antibiotic or benzoyl peroxide) Or Topical retinoid + oral antibiotic + benzoyl peroxide Or (additional options for female patients) Combination oral contraceptive Androgen receptor antagonist Nodular acne Isotretinoin  ogic Therapy for Comedon acol al acn arm e Ph  1-Topical Retinoids (Vitamin A analogs) Mechanism of action: 1. Retinoids are active keratolytics (the most potent comedolytic agents). 2. Retinoids reduce obstruction within the follicle and are useful for both comedonal and inflammatory acne. 3. They inhibit microcomedone formation, decreasing the number of mature comedones and inflammatory lesions. 4. Topical retinoids have no antibacterial properties. N.B.: Retinoids should be applied at bedtime (to avoid degradation in ultraviolet light), a half-hour after cleansing, starting with every other night for 1 to 2 weeks to avoid irritation and hyperpigmentation. Doses can be increased only after beginning with 4 to 6 weeks.  Topical Retinoids…….cont’d 1. Tretinoin: (1st generation retinoic acid and vitamin A acid). It should not be used in pregnant women because of risk to the fetus. 2. Adapalene (Differin): is the topical retinoid of first choice for both treatment and maintenance therapy because it is effective comedolytic and anti-inflammatory agent but less irritating than other topical retinoids. Adapalene should be considered for patients with darker skin tones secondary to the reduced risk for hyperpigmentation. 3. Tazarotene (Tazorac): (2nd generation topical retinoid) Compared with tretinoin, it is as effective for comedonal and more effective for inflammatory lesions when applied once daily but less tolerated.  2-Azelaic acid (Azelex) Azelaic acid 20% is a dicarboxylic acid. It has antibacterial, antiinflammatory, and comedolytic activity. It has limited efficacy compared with other therapies. It is an alternative to topical retinoids for maintenance therapy for patients who are unable to tolerate it.  3-Salicylic Acid Wash Mild comedolytic and keratolytic agent available for nonprescription use in concentrations ranging from 0.5% - 2%. It provides a milder, less effective, alternative to the prescription agent tretinoin. It also is considered to be less effective than benzoyl peroxide. Salicylic acid is applied once or twice daily, usually in a gel formulation, to the entire area. Use should be limited to once daily or every other day if excessive peeling occurs. The chronic use over large body surfaces may increases the risk of systemic salicylate toxicity.  gic Therapy for Maculopapu acolo lar a arm cne h P  1-ANTIBIOTICS Antibiotics do not resolve existing lesions, but they can prevent future lesions by decreasing both P. acnes colonization and inflammation. Antibiotics inhibit the release of reactive oxygen species by P. acnes , which in turn reduces leukocyte recruitment. Successful antibiotic courses do not necessarily eradicate P. acnes.  A. Topical Antibiotics Topically applied antibiotics avoid systemic exposure and achieve high follicular concentrations with minimal adverse effects. Topical antibiotics alone in acne treatment should be avoided due to concerns for bacterial resistance. So, A. They can augment topical retinoids when initiating therapy for comedonal and papular acne cases involving inflammatory lesions B. they can be added to regimens for patients failing monotherapy. Topical antibiotics are usually applied once or twice daily for 3 months, followed by continuation of a topical retinoid for maintenance therapy. Clindamycin and erythromycin are commonly used agents.  B. Oral Antibiotics Oral antibiotics should not be used as monotherapy. If lesions are widespread or difficult to reach, oral antibiotics are generally preferred over topical agents. They are also used as a step-up therapy when topical antibiotic regimens fail to suppress acne.  Examples of oral Antibiotics 1. Doxycycline is most convenient and effective 2. Tetracycline is used as an alternative. C.I.: a. Tetracyclines should not be prescribed for children younger than 9 years of age because of potential impairment of bone growth and discoloration of forming teeth. b. Pregnant women must avoid tetracyclines because of bone growth effects on the fetus. 3. Minocycline (in tetracyclines failure): it is more expensive with lower efficacy and a higher rate of serious adverse effects than other tetracycline antibiotics. 4. Trimethoprim/sulfamethoxazole (for situations when other antibiotics are unable to be used): effective, but has a less favorable adverse effect when compared to tetracycline. 5. Erythromycin may be an alternative option In patients who are unable to take other oral antibiotics despite association with higher rates of resistance.  To Minimize Resistance Antibiotics should be reserved for acne of at least maculopapular subtype Antibiotics should be used with drugs exerting additional mechanisms of action (topical retinoids) rather than used as monotherapy should be used for the shortest effective duration ( 3 months) to obtain acne control Antibiotics should not be used for maintenance of control if antibiotic therapy needs to be continued beyond 3 months to maintain control, add benzoyl peroxide  2-Benzoyl Peroxide The MOST effective nonprescription medication currently available for the treatment of noninflammatory acne. This is due to: - Inhibits the growth of P. acnes by generating free radicals that oxidize protein in the cell membrane. - Not antibiotic but it has antibacterial activity (Prevent or eliminate the development of P. acnes resistance of bacteria), and it often is used in conjunction with topical or oral antibiotics. - Acts as a keratolytic by reducing follicular hyperkeratosis. - It has also anti-inflammatory activity. Available for nonprescription use in concentrations ranging from 2.5% to 10%. It should be applied in a thin layer to the entire affected area. Some mild stinging or peeling is normal and usually diminishes with continued use.  Benzoyl Peroxide Patients should be cautioned that benzoyl peroxide may cause bleaching of hair, clothing, bed linens, and towels. Benzoyl peroxide also may cause increased sensitivity to the sun. Patients should be advised to avoid excessive sun exposure and to use a sunscreen product with a sun protection factor (SPF) of 15 or higher when going outdoors. Pregnant women often have problems with acne as a result of hormonal imbalances. Benzoyl peroxide is a Pregnancy Category C medication and should be used only with the knowledge and consent of the patient’s obstetrician or primary care provider.  3- Hormonal Therapies (anti-androgenic drugs) 1. Androgen Receptor Antagonists 2. Combination Oral Contraceptives  A. Androgen Receptor Antagonists Spironolactone at doses of 25 to 100 mg/day reduces acne because it is an androgen receptor antagonist. Spironolactone is generally well tolerated, although gynecomastia, menstrual irregularities, and hyperkalemia are possible. Tolerability and serum potassium should be monitored every 3 weeks until maximum tolerated dose or 100 mg/day is achieved. Spironolactone should be used with caution in male patients given the risk for gynecomastia and possibly lower efficacy when compared to female patients  B. Combination Oral Contraceptives Oral contraceptives (norgestimate with ethinyl estradiol , or norethindrone acetate with ethinyl estradiol), improves acne in females by reducing ovarian androgen production and by increasing sex hormone-binding globulin concentrations in the serum, thereby lowering free testosterone levels. Products containing progestins with androgenic effects (e.g., norgestrel, levonorgestrel) may override the effect of ethinyl estradiol and worsen acne.  ologic Therapy for Nodular Ac rmac n ha e P  Oral Isotretinoin It exhibits all four of the mechanisms of action currently used to attack acne, making it a uniquely effective monotherapy. 5-month-long course of therapy will induce a remission lasting for several months or even years. It should be reserved as a last-line therapy for patients with nodular acne due to its adverse effect profile.  Oral Isotretinoin Adverse Effects: Approximately 90% of patients experience mucocutaneous effects including dryness, erythema, peeling and photosensitivity. Other common side effects include hair dryness, hair thinning and nail fragility. Isotretinoin may cause depression, including suicide attempts, psychosis, and violent behavior. Isotretinoin is severely teratogenic.  A Food and Drug Administration-mandated Risk Evaluation Mitigation Strategy (REMS) strict risk management program called iPLEDGE regulates the prescription and distribution of isotretinoin in the United States. The goals of iPLEDGE are to ensure that women using isotretinoin do not become pregnant and that women who are pregnant do not use isotretinoin.  iPLEDGE Program The program requires that all female patients of childbearing potential must have two negative pregnancy tests before initiating isotretinoin therapy, one at the time of screening and then another after 1 month of using their chosen contraception regimen. The program also requires a negative pregnancy test before each monthly refill is prescribed, immediately after therapy, and a month after therapy.  iPLEDGE Program Patients (both male and female) should also be counseled not to donate blood during therapy and for at least a month after therapy, to ensure no pregnant woman receives isotretinoin- contaminated blood products. Female patients of childbearing potential must use two forms of contraception for at least a month before, during, and a month after isotretinoin therapy  Isotretinoin monitoring Before beginning isotretinoin therapy, all patients, both male and female, should have the following baseline laboratory tests: (a fasting lipid panel; a liver function panel; and a complete blood count, including platelets). Monthly monitoring should continue throughout isotretinoin therapy. N.B.: If triglyceride levels exceed from 700 to 800 mg/dL, isotretinoin should be discontinued, or continued at a reduced dosage with concomitant gemfibrozil therapy to reduce the risk of pancreatitis. If pancreatitis develops, isotretinoin must be discontinued. Liver function tests and blood counts only need to be redrawn during therapy if symptoms suggestive of hepatitis or blood dyscrasias appear.  Isotretinoin’s adverse effects and treatment strategies 1. Use artificial tears for dry eyes; if the dryness still after several days, apply lubricating ophthalmic ointment at bedtime. 2. apply moisturizer to dry skin 3. Frequent application of a lip balm or emollient, ideally one containing sunscreen, will treat cheilitis. 4. If the symptoms become intolerable, a small reduction in the isotretinoin dose (e.g., reduction of 10–20 mg/day) usually decreases the intensity of skin and mucous membrane reactions. 5. Drug discontinuation is rarely necessary [email protected] 66