Self-Treatment of Acne, Self-Treatment of Acne, Dermatitis, and General Dermatitis, and General

Skin CareSkin CareJohn Pedey-BraswellJohn Pedey-Braswell

2005 Pharm.D. Candidate2005 Pharm.D. CandidateUniversity of Washington School of Pharmacy University of Washington School of Pharmacy

Pharmacy 301Pharmacy 301June 4, 2003June 4, 2003

tafkab@u.washington.edutafkab@u.washington.edu

Lecture OverviewLecture Overview

Skin Anatomy and PhysiologySkin Anatomy and Physiology

AcneAcne

Dermatitis and Dry SkinDermatitis and Dry Skin

Skin FactsSkin Facts

Largest Organ in the Body.Largest Organ in the Body.

Variable Thickness, averages about 1-2mm.Variable Thickness, averages about 1-2mm.

Skin, Hair, and Nails serve as protective barrier Skin, Hair, and Nails serve as protective barrier between body and environment.between body and environment.

Success of protection depends on age, Success of protection depends on age, immunologic status, underlying disease states, immunologic status, underlying disease states, use of certain medications, and preservation of use of certain medications, and preservation of intact stratum corneum (outermost dead layer).intact stratum corneum (outermost dead layer).

The SkinThe Skin

Three LayersThree Layersepidermisepidermisdermisdermishypodermishypodermis

GlandsGlandssebaceoussebaceoussweatsweat

HypodermisHypodermis

Also known as subcutaneous tissue, is the Also known as subcutaneous tissue, is the innermost area of skin.innermost area of skin.

Consists of loose connective tissue and adipose Consists of loose connective tissue and adipose firmly anchored to the dermis above it.firmly anchored to the dermis above it.

Varying thickness allows necessary pliability of Varying thickness allows necessary pliability of human skin.human skin.

Fatty component facilitates thermal control, Fatty component facilitates thermal control, holds food reserve, and provides cushioning or holds food reserve, and provides cushioning or padding.padding.

The SkinThe Skin

Three LayersThree Layersepidermisepidermisdermisdermishypodermishypodermis

GlandsGlandssebaceoussebaceoussweatsweat

DermisDermis

Approximately 40 times thicker than the Approximately 40 times thicker than the epidermis above.epidermis above.

Consists of elastic and connective tissue Consists of elastic and connective tissue (collagen and elastin) surrounded by a (collagen and elastin) surrounded by a mucopolysaccharide substance.mucopolysaccharide substance.

Fibroblasts, mast cells, nerves, blood supply.Fibroblasts, mast cells, nerves, blood supply.

Sensation of itching arises in upper portion, Sensation of itching arises in upper portion, stinging in middle region, pain in the lowest stinging in middle region, pain in the lowest level.level.

The SkinThe Skin

Three LayersThree Layersepidermisepidermisdermisdermishypodermishypodermis

GlandsGlandssebaceoussebaceoussweatsweat

EpidermisEpidermis

Outermost layer consisting of compact, Outermost layer consisting of compact, avascular stratified epitheal cellsavascular stratified epitheal cellsFive distinct layers (from bottom to top): strata Five distinct layers (from bottom to top): strata germinativum, spinosum, granulosum, lucidum, germinativum, spinosum, granulosum, lucidum, corneum.corneum.Keratinocytes in the stratum germinativum divide Keratinocytes in the stratum germinativum divide and move upwards to the skin surface. In the and move upwards to the skin surface. In the process, they change from living cells to dead, process, they change from living cells to dead, thick-walled, flat, nonnucleated cells that thick-walled, flat, nonnucleated cells that contain keratin (a fibrous, insoluble protein).contain keratin (a fibrous, insoluble protein).Melanin is produced in stratum spinosum.Melanin is produced in stratum spinosum.

Stratum CorneumStratum CorneumComposed of flat, scaly, dead (keratinized) tissue.Composed of flat, scaly, dead (keratinized) tissue.Outermost cells are flat plates that are constantly Outermost cells are flat plates that are constantly shed (desquamated) and replaced by new cells shed (desquamated) and replaced by new cells continually generated by mitotic processes in the continually generated by mitotic processes in the basal cell layer. basal cell layer. Complete cycle from basal cell formation to shedding Complete cycle from basal cell formation to shedding is 28 to 45 days.is 28 to 45 days.Flexibility of this layer depends on its water content, Flexibility of this layer depends on its water content, which is normally 10-20% by weight. Influenced by which is normally 10-20% by weight. Influenced by humidity, temperature, surfactants, and trauma.humidity, temperature, surfactants, and trauma.Keratin can absorb many times its weight in water, Keratin can absorb many times its weight in water, and thus retains water to maintain the skin’s flexibility and thus retains water to maintain the skin’s flexibility and integrity.and integrity.When the skin’s water content drops below 10%, When the skin’s water content drops below 10%, chapping occurs and the stratum corneum becomes chapping occurs and the stratum corneum becomes brittle and cracks easily – allowing irritants and brittle and cracks easily – allowing irritants and bacteria to penetrate more easily, leading to bacteria to penetrate more easily, leading to inflammation and possibly infection.inflammation and possibly infection.

Acne vulgaris (common acne)Acne vulgaris (common acne)

Most common adolescent skin disorder, often linked to Most common adolescent skin disorder, often linked to the onset of puberty.the onset of puberty.Approximately 85% of all people between ages 12-24 Approximately 85% of all people between ages 12-24 years will develop it to some degree.years will develop it to some degree.Onset in males is typically between 16-18 years. Usually Onset in males is typically between 16-18 years. Usually clears by the mid-20s.clears by the mid-20s.Female onset is usually 15-17 years. Unfortunately, may Female onset is usually 15-17 years. Unfortunately, may persist into 30s or 40s, and worsen in menopause.persist into 30s or 40s, and worsen in menopause.First lesions may precede other signs of puberty and First lesions may precede other signs of puberty and diagnosed as early as age 7 years.diagnosed as early as age 7 years.Papular lesions generally appear during the mid-teen Papular lesions generally appear during the mid-teen years, while nodular lesions appear in the late teens.years, while nodular lesions appear in the late teens.

Dermal Pilosebaceous UnitsDermal Pilosebaceous Units

Acne vulgaris has its origin in Acne vulgaris has its origin in these units.these units.Consist of a hair follicle and Consist of a hair follicle and associated sebaceous glands.associated sebaceous glands.Connected to the skin surface Connected to the skin surface by the infundibulum – an by the infundibulum – an epithelial tissue lined duct epithelial tissue lined duct through which the hair shaft through which the hair shaft passes.passes.Sebaceous glands produce Sebaceous glands produce sebum, which passes to skin sebum, which passes to skin surface through infundibulum surface through infundibulum then spreads over the skin to then spreads over the skin to retard water loss and maintain retard water loss and maintain hydration of skin and hair.hydration of skin and hair.Glands are more common on Glands are more common on the face, back, and chest – the face, back, and chest – and so is acne.and so is acne.

Typical Distribution of Typical Distribution of Pilosebaceous UnitsPilosebaceous Units

Source: skincarephysicians.comSource: skincarephysicians.com

Origins of Acne VulgarisOrigins of Acne Vulgaris

Production of androgenic hormones increases as a male Production of androgenic hormones increases as a male or female approaches puberty. Precise cause of acne is or female approaches puberty. Precise cause of acne is not known, but believed to be linked to this increase and not known, but believed to be linked to this increase and closely related to acne development.closely related to acne development.Androgenic hormones stimulate the sebaceous glands – Androgenic hormones stimulate the sebaceous glands – appearance of acne usually noticed at actual onset of appearance of acne usually noticed at actual onset of puberty.puberty.Four processes linked to increase in androgens are Four processes linked to increase in androgens are closely related to acne development:closely related to acne development:

1. Abnormal keratinization of cells in the infundibulum;1. Abnormal keratinization of cells in the infundibulum; 2. Increase in sebum production;2. Increase in sebum production; 3. Accelerated growth in 3. Accelerated growth in Propionibacterium acnesPropionibacterium acnes;; 4. Occurrence of inflammation.4. Occurrence of inflammation.

A Zit is BornA Zit is Born

Abnormal keratinization of cells in the infundibulum leads Abnormal keratinization of cells in the infundibulum leads to increased cohesiveness between the cells, and results to increased cohesiveness between the cells, and results in obstruction of the follicle rather than the removal of in obstruction of the follicle rather than the removal of these cells to the skin surface.these cells to the skin surface.The trapped, keratinized cells plug and distend the The trapped, keratinized cells plug and distend the follicle to form a microcomedo, the initial lesion of acne.follicle to form a microcomedo, the initial lesion of acne.As more cells and sebum accumulate, microcomedo As more cells and sebum accumulate, microcomedo enlarges and becomes visible as a closed comedo or enlarges and becomes visible as a closed comedo or whitehead. This is the precursor to other developing whitehead. This is the precursor to other developing acne lesions.acne lesions.Hair in follicle can determine extent of comedo formation. Hair in follicle can determine extent of comedo formation. Thin and small hairs can become trapped in the plug, Thin and small hairs can become trapped in the plug, while thick, heavier hairs (like on the scalp or in the while thick, heavier hairs (like on the scalp or in the beard) will push the plug to the surface, thus preventing beard) will push the plug to the surface, thus preventing comedo formation.comedo formation.

More on Zit FormationMore on Zit Formation

Open comedones, or blackheads, occur when sufficient Open comedones, or blackheads, occur when sufficient material accumulates behind the plug, and the orifice of material accumulates behind the plug, and the orifice of the follicular canal becomes distended, allowing the plug the follicular canal becomes distended, allowing the plug to protrude. The tip of the plug of the open comedo may to protrude. The tip of the plug of the open comedo may darken because of melanin content.darken because of melanin content.Increase in circulating androgens stimulates the Increase in circulating androgens stimulates the production of sebum, which is prevented from reaching production of sebum, which is prevented from reaching the surface of the skin by the obstructing keratinized the surface of the skin by the obstructing keratinized cells. At the same time the bacteria cells. At the same time the bacteria P.acnes P.acnes undergoes undergoes accelerated growth.accelerated growth.P.acnes P.acnes is a major contributor to inflammatory acne is a major contributor to inflammatory acne lesions due to lipase production and breakdown of lesions due to lipase production and breakdown of sebum to free fatty acids. Colony counts are higher in sebum to free fatty acids. Colony counts are higher in patients with acne than in those without it. Resulting patients with acne than in those without it. Resulting inflammation causes localized tissue distruction.inflammation causes localized tissue distruction.

Inflammatory AcneInflammatory Acne

Begins with closed comedones that distend the follicle, Begins with closed comedones that distend the follicle, causing the cellular lining of the walls to spread and causing the cellular lining of the walls to spread and become thin.become thin.Primary inflammation of the follicle wall develops with the Primary inflammation of the follicle wall develops with the disruption of the epitheleal lining and lymphocyte disruption of the epitheleal lining and lymphocyte infiltration.infiltration.Severe inflammatory reaction follows if the follicle wall Severe inflammatory reaction follows if the follicle wall ruptures spontaneously or is ruptured by picking, ruptures spontaneously or is ruptured by picking, squeezing, attempted extraction by dermatologist, or if squeezing, attempted extraction by dermatologist, or if contents are discharged into the surrounding tissue. contents are discharged into the surrounding tissue. May result in abscesses, which can cause scars or pits May result in abscesses, which can cause scars or pits after healing.after healing.Pustules or purulent nodules are more likely to cause Pustules or purulent nodules are more likely to cause permanent scarring.permanent scarring.

A Picture is Worth a Thousand A Picture is Worth a Thousand WordsWords

FIGURE 1. FIGURE 1. Stages of Stages of acne. acne. (A)(A) Normal Normal follicle; follicle; (B)(B) open open comedo (blackhead); comedo (blackhead); (C)(C) closed comedo closed comedo (whitehead); (whitehead); (D)(D) papule; papule; (E)(E) pustule. pustule.

Source: American Source: American Academy of Family Academy of Family Physicians.Physicians.

Closed Comedones Closed Comedones (Whiteheads)(Whiteheads)

(L):skincarephysicians.com (R): dermatlas.med.jhmi.edu(L):skincarephysicians.com (R): dermatlas.med.jhmi.edu

Open Comedones (Blackheads)Open Comedones (Blackheads)

(L):dermatlas.med.jhmi.edu (R):medlib.med.utah.edu/kw/derm(L):dermatlas.med.jhmi.edu (R):medlib.med.utah.edu/kw/derm

Inflammatory Acne: PapulesInflammatory Acne: Papules

A papule is defined as a A papule is defined as a small (5 millimeters or less), small (5 millimeters or less), solid lesion slightly elevated solid lesion slightly elevated above the surface of the above the surface of the skin. A group of very small skin. A group of very small papules and papules and microcomedones may be microcomedones may be almost invisible but have a almost invisible but have a "sandpaper" feel to the "sandpaper" feel to the touch. A papule is caused by touch. A papule is caused by localized cellular reaction to localized cellular reaction to the process of acne. This the process of acne. This photo shows papules and photo shows papules and comedones on the face of an comedones on the face of an acne patient.acne patient.

Source:skincarephysicians.comSource:skincarephysicians.com

Inflammatory Acne: PustulesInflammatory Acne: Pustules

A dome-shaped, fragile lesion A dome-shaped, fragile lesion containing pus that typically containing pus that typically consists of a mixture of white consists of a mixture of white blood cells, dead skin cells, blood cells, dead skin cells, and bacteria. A pustule that and bacteria. A pustule that forms over a sebaceous follicle forms over a sebaceous follicle usually has a hair in the usually has a hair in the center. Acne pustules that heal center. Acne pustules that heal without progressing to cystic without progressing to cystic form usually leave no scars. form usually leave no scars. This photo shows pustules, This photo shows pustules, papules and comedones on papules and comedones on the face of an acne patient.the face of an acne patient.

Source: skincarephysicians.comSource: skincarephysicians.com

Inflammatory Acne: MaculesInflammatory Acne: Macules

A macule is the temporary red A macule is the temporary red spot left by a healed acne spot left by a healed acne lesion. It is flat, usually red or lesion. It is flat, usually red or red-pink, with a well defined red-pink, with a well defined border. A macule may persist border. A macule may persist for days to weeks before for days to weeks before disappearing. When a number disappearing. When a number of macules are present at one of macules are present at one time they can contribute to the time they can contribute to the "inflamed face" appearance of "inflamed face" appearance of acne. This photo shows the acne. This photo shows the "red face" appearance of acne "red face" appearance of acne with macules.with macules.

Source: skincarephysicians.comSource: skincarephysicians.com

Inflammatory Acne: NodulocysticInflammatory Acne: NodulocysticLike a papule, a nodule is a solid, dome-Like a papule, a nodule is a solid, dome-shaped or irregularly-shaped lesion. shaped or irregularly-shaped lesion. Unlike a papule, a nodule is Unlike a papule, a nodule is characterized by inflammation, extends characterized by inflammation, extends into deeper layers of the skin and may into deeper layers of the skin and may cause tissue destruction that results in cause tissue destruction that results in scarring. A nodule may be very painful. scarring. A nodule may be very painful. Nodular acne is a severe form of acne Nodular acne is a severe form of acne that may not respond to therapies other that may not respond to therapies other than isotretinoin.than isotretinoin.A cyst is a sac-like lesion containing A cyst is a sac-like lesion containing liquid or semi-liquid material consisting liquid or semi-liquid material consisting of white blood cells, dead cells, and of white blood cells, dead cells, and bacteria. It is larger than a pustule, may bacteria. It is larger than a pustule, may be severely inflamed, extends into be severely inflamed, extends into deeper layers of the skin, may be very deeper layers of the skin, may be very painful, and can result in scarring. Cysts painful, and can result in scarring. Cysts and nodules often occur together in a and nodules often occur together in a severe form of acne called nodulocystic. severe form of acne called nodulocystic. Systemic therapy with isotretinoin is Systemic therapy with isotretinoin is sometimes the only effective treatment sometimes the only effective treatment for nodulocystic acne. for nodulocystic acne.

Source: skincarephysicians.com Source: skincarephysicians.com

What About Rosacea?What About Rosacea?Referred to as "adult acne," rosacea causes facial swelling and Referred to as "adult acne," rosacea causes facial swelling and redness and therefore, is easy to confuse with other skin redness and therefore, is easy to confuse with other skin conditions, such as acne or sunburn. conditions, such as acne or sunburn. Those who have rosacea might first notice a tendency to flush or Those who have rosacea might first notice a tendency to flush or blush easily. The condition can occur over a long period of time blush easily. The condition can occur over a long period of time and often progresses to a persistent redness, pimples and visible and often progresses to a persistent redness, pimples and visible blood vessels in the center of the face that might eventually blood vessels in the center of the face that might eventually involve the cheeks, forehead, chin and nose. Other areas that involve the cheeks, forehead, chin and nose. Other areas that can be affected by rosacea are the neck, ears, chest and back. can be affected by rosacea are the neck, ears, chest and back. Sometimes, rosacea affects the eyes. Sometimes, rosacea affects the eyes. The pimples of rosacea, which often occur as the disease has The pimples of rosacea, which often occur as the disease has progressed, are different than those of acne because blackheads progressed, are different than those of acne because blackheads and whiteheads rarely appear. Rather, people who have rosacea and whiteheads rarely appear. Rather, people who have rosacea have visible small blood vessels and their pimples—some have visible small blood vessels and their pimples—some containing pus—appear as small, red bumps. containing pus—appear as small, red bumps. Rosacea can be controlled with medications and lifestyle Rosacea can be controlled with medications and lifestyle changes. Early intervention by a dermatologist, the expert in skin, changes. Early intervention by a dermatologist, the expert in skin, hair and nail conditions, is key to successful treatment. Delay in hair and nail conditions, is key to successful treatment. Delay in diagnosis and treatment because of non-physician treatments diagnosis and treatment because of non-physician treatments can result in scarring.can result in scarring.

Things Proven to Make Acne Things Proven to Make Acne WorseWorse

Heredity – chances of offspring developing acne are Heredity – chances of offspring developing acne are higher when both parents have had acne than when only higher when both parents have had acne than when only one parent has the disorder. one parent has the disorder. Skin Hydration – decreases the size of the pilosebaceous Skin Hydration – decreases the size of the pilosebaceous duct orifice. Acne can be worsened by high humidity duct orifice. Acne can be worsened by high humidity environments and tight-fitting clothing.environments and tight-fitting clothing.Local irritation (acne mechanica) – occlusive clothing, Local irritation (acne mechanica) – occlusive clothing, headbands, helmets, chin straps can aggravate acne.headbands, helmets, chin straps can aggravate acne.Exposure to dirt, vaporized cooking oils, industrial Exposure to dirt, vaporized cooking oils, industrial chemicals may cause occupational acne.chemicals may cause occupational acne.Acne cosmetica is a mild form of acne on the face, cheek, Acne cosmetica is a mild form of acne on the face, cheek, and chin. Typically closed, noninflammatory comedones. and chin. Typically closed, noninflammatory comedones. Oil-based cosmetics, including shampoos, may be Oil-based cosmetics, including shampoos, may be occlusive and plug the follicles, exacerbating or even occlusive and plug the follicles, exacerbating or even initiating acne.initiating acne.

Unsubstantiated FactorsUnsubstantiated Factors

ChocolateChocolateNutsNutsFatsFatsColasColasCarbohydratesCarbohydratesSexual Activity – acne begins at puberty and Sexual Activity – acne begins at puberty and sexual activity may begin at the same time, but sexual activity may begin at the same time, but not a cause and effect relationship.not a cause and effect relationship.

Treatment ApproachesTreatment Approaches

Goals are to unblock pilosebaceous ducts and keep Goals are to unblock pilosebaceous ducts and keep orifices open, plus avoiding factors that worsen acne.orifices open, plus avoiding factors that worsen acne.Talk with your pharmacist. Some medications such as Talk with your pharmacist. Some medications such as corticosteroids (prednisone, et al) can cause acne. She, corticosteroids (prednisone, et al) can cause acne. She, or he, can help with self-care product selection and or he, can help with self-care product selection and provide feedback.provide feedback.Self-treatment is appropriate for mild-to-moderate Self-treatment is appropriate for mild-to-moderate noninflammatory acne (open or closed comedones).noninflammatory acne (open or closed comedones).Do NOT add nonprescription medications to prescribed Do NOT add nonprescription medications to prescribed regimens unless recommended by prescriber.regimens unless recommended by prescriber.

Proper Skin CleansingProper Skin CleansingRemoving excess sebum from the skin in a program of daily Removing excess sebum from the skin in a program of daily washing produces a mild drying of the skin and, perhaps, mild washing produces a mild drying of the skin and, perhaps, mild erythema.erythema.Affected areas should be washed at least twice daily (more Affected areas should be washed at least twice daily (more frequently if skin is oily) with warm water, medicated or frequently if skin is oily) with warm water, medicated or unmedicated soap, and a soft washcloth; then patted dry.unmedicated soap, and a soft washcloth; then patted dry.Washing should not be excessively vigorous; it should cause Washing should not be excessively vigorous; it should cause barely noticeable peeling that can loosen comedonesbarely noticeable peeling that can loosen comedonesWashing intensity and frequency should be reduced and a less Washing intensity and frequency should be reduced and a less drying soap considered if tautness occurs.drying soap considered if tautness occurs.Facial soaps that do not contain moisturizing oils are usually Facial soaps that do not contain moisturizing oils are usually satisfactory. A certain degree of drying action is desirable, so satisfactory. A certain degree of drying action is desirable, so facial soap should be tried before surfactant soap substitutes. facial soap should be tried before surfactant soap substitutes. Antibacterial soaps have no clinical value. Antibacterial soaps have no clinical value. Salicylic acid, sulfur, and resorcinol are safe and effective for Salicylic acid, sulfur, and resorcinol are safe and effective for treating acne, but their effectiveness as soaps is questionable treating acne, but their effectiveness as soaps is questionable because little, if any, residue is left on the skin after washing. because little, if any, residue is left on the skin after washing. Abrasive agents may be useful in treating noninflammatory acne, Abrasive agents may be useful in treating noninflammatory acne, but avoid in inflammatory acne because of increased irritation.but avoid in inflammatory acne because of increased irritation.If inconvenient to wash during the day, cleansing pads can be If inconvenient to wash during the day, cleansing pads can be used at school or work.used at school or work.

Benzoyl PeroxideBenzoyl PeroxideAvailable in diverse dosage forms such as lotions, gels, creams, Available in diverse dosage forms such as lotions, gels, creams, cleansers, masks, and soaps.cleansers, masks, and soaps.Different formulations are not equivalent – the drying effect of the Different formulations are not equivalent – the drying effect of the gel base is superior to a lotion or cream of the same strength gel base is superior to a lotion or cream of the same strength (most gels are Rx only). Washes and cleansers are widely used (most gels are Rx only). Washes and cleansers are widely used as treatment adjuncts, but have little or no comedolytic effect.as treatment adjuncts, but have little or no comedolytic effect.Causes irritation and desquamation that prevents closure of the Causes irritation and desquamation that prevents closure of the pilosebaceous orifice.pilosebaceous orifice.Irritant effect causes an increased turnover rate of epithelial cells Irritant effect causes an increased turnover rate of epithelial cells lining the follicular duct, which increases sloughing and promotes lining the follicular duct, which increases sloughing and promotes resolution of the comedones. May take 4-6 weeks see full effect.resolution of the comedones. May take 4-6 weeks see full effect.Its oxidizing potential may contribute to antibacterial activity Its oxidizing potential may contribute to antibacterial activity against against P.acnesP.acnes. . AEs: excessive dryness, peeling, skin sloughing, edema indicate AEs: excessive dryness, peeling, skin sloughing, edema indicate that lower concentrations should be used for shorter periods of that lower concentrations should be used for shorter periods of time. Can cause transient stinging or burning.time. Can cause transient stinging or burning.May bleach hair or clothing.May bleach hair or clothing.Avoid excessive exposure to sun or tanning beds – may enhance Avoid excessive exposure to sun or tanning beds – may enhance the ability of UV rays to produce skin cancer.the ability of UV rays to produce skin cancer.

Salicylic Salicylic Acid/Sulfur/ResorcinolAcid/Sulfur/Resorcinol

Salicylic acid is a mild comedolytic agent, available in Salicylic acid is a mild comedolytic agent, available in nonprescription acne products.nonprescription acne products.Acts as surface keratolytic, and enhances absorption Acts as surface keratolytic, and enhances absorption of other agents. of other agents. Considered adjunctive therapy, but cleansing pads Considered adjunctive therapy, but cleansing pads are safe, effective, and superior to benzoyl peroxide are safe, effective, and superior to benzoyl peroxide in preventing and clearing both comedones and in preventing and clearing both comedones and inflammatory lesions of acne.inflammatory lesions of acne.Precipitated, or colloidal, sulfur is in products as a Precipitated, or colloidal, sulfur is in products as a keratolytic agent. Effective agent for resolving keratolytic agent. Effective agent for resolving existing comedones, but continued use may have existing comedones, but continued use may have comedogenic effect.comedogenic effect.Noticeable odor and color makes sulfur products a Noticeable odor and color makes sulfur products a tough sell for consumers.tough sell for consumers.Resorcinol not recognized as safe and effective by Resorcinol not recognized as safe and effective by the FDA, unless in combination with sulfur – probably the FDA, unless in combination with sulfur – probably enhances keratolytic effect.enhances keratolytic effect.

Prescription Remedies: AntibioticsPrescription Remedies: Antibiotics

Used to control growth of bacteria Used to control growth of bacteria Propionibacterium Propionibacterium acnesacnes in pilosebaceous ducts. in pilosebaceous ducts.

Comedonal acne can usually be controlled with topical Comedonal acne can usually be controlled with topical antibiotics such as clindamycin or erythromycin.antibiotics such as clindamycin or erythromycin.

Inflammatory acne often needs systemic antibiotic Inflammatory acne often needs systemic antibiotic therapy with a tetracycline (tetracycline, doxycycline, or therapy with a tetracycline (tetracycline, doxycycline, or minocycline), erythromycin, or rarely ampicillin. minocycline), erythromycin, or rarely ampicillin.

Prescription Remedies: HormonalPrescription Remedies: Hormonal

Oral contraceptives may be useful adjunctive therapy for Oral contraceptives may be useful adjunctive therapy for all types of acne in females.all types of acne in females.Sebum production is controlled by androgens, and oral Sebum production is controlled by androgens, and oral contraceptives are known to reduce androgen levels by contraceptives are known to reduce androgen levels by increasing sex hormone binding globulin levels – increasing sex hormone binding globulin levels – reduces the availability of biologically active free reduces the availability of biologically active free androgens.androgens.Pills containing norgestimate or desogestrel (Ortho Tri-Pills containing norgestimate or desogestrel (Ortho Tri-Cyclen, Ortho Cyclen, Desogen) appear to work best.Cyclen, Ortho Cyclen, Desogen) appear to work best.Two to four monthes therapy may be required before Two to four monthes therapy may be required before improvement is seen, and relapses are common if improvement is seen, and relapses are common if medication is discontinued.medication is discontinued.The diuretic spironolactone is also used to control The diuretic spironolactone is also used to control androgen levels.androgen levels.

Prescription Remedies: Prescription Remedies: TretinoinTretinoin

Tretinoin (Retin-A®): all-trans-retinoic acid.Tretinoin (Retin-A®): all-trans-retinoic acid.Used primarily in topical treatment of acne vulgaris when Used primarily in topical treatment of acne vulgaris when comedones, papules, and pustules predominate.comedones, papules, and pustules predominate.Appears to stimulate mitosis and turnover of follicular Appears to stimulate mitosis and turnover of follicular epithelial cells and reduce their cohesiveness, facilitating epithelial cells and reduce their cohesiveness, facilitating extrusion of existing comedones and preventing extrusion of existing comedones and preventing formation of new ones. May take 6-8 weeks to see formation of new ones. May take 6-8 weeks to see noticeable results.noticeable results.Skin irritant: may cause transitory stinging and feeling of Skin irritant: may cause transitory stinging and feeling of warmth. Normal use produces some erythema and warmth. Normal use produces some erythema and peeling similar to that of a mild sunburn. Avoid contact peeling similar to that of a mild sunburn. Avoid contact with mucous membranes and eyes.with mucous membranes and eyes.Some patients will experience edema, blistering, and Some patients will experience edema, blistering, and crusting of the skin. Photosensitivity may occur, as well crusting of the skin. Photosensitivity may occur, as well as temporary hypo- or hyperpigmentation.as temporary hypo- or hyperpigmentation.Contraindicated in pregnancy, some case reports of Contraindicated in pregnancy, some case reports of congenital abnormalities. See isotretinoin.congenital abnormalities. See isotretinoin.

Prescription Remedies: tazorotene Prescription Remedies: tazorotene and adapaleneand adapalene

Tazarotene (Tazorac®):Tazarotene (Tazorac®): prodrug that is de-esterified in prodrug that is de-esterified in the skin to release active drug tazorotenic acid (a the skin to release active drug tazorotenic acid (a retinoid). Same action, AEs, contraindications as retinoid). Same action, AEs, contraindications as tretinoin.tretinoin.Available as 0.1% gel or cream.Available as 0.1% gel or cream.Adapalene (Differin®):Adapalene (Differin®): retinoid analog, a naphthoic acid retinoid analog, a naphthoic acid derivative. Same action, AEs as tretinoin, derivative. Same action, AEs as tretinoin, HOWEVERHOWEVER no evidence that it is harmful to fetus.no evidence that it is harmful to fetus.Available as 0.1% cream, solution, or gel.Available as 0.1% cream, solution, or gel.

Prescription Remedies: isotretinoinPrescription Remedies: isotretinoinIsotretinoin (Accutane®): 13-cis-retinoic acid. Generic Isotretinoin (Accutane®): 13-cis-retinoic acid. Generic version now available. 10mg, 20mg, 40mg capsules.version now available. 10mg, 20mg, 40mg capsules.Used in severe inflammatory acne after all other Used in severe inflammatory acne after all other methods exhausted. Also used to treat some cancers.methods exhausted. Also used to treat some cancers.Probably works on similar transcription pathways as Probably works on similar transcription pathways as tretinoin. Dose-related reduction in sebum excretion, tretinoin. Dose-related reduction in sebum excretion, and subsequent decrease in and subsequent decrease in P.acnesP.acnes growth. Dosed by growth. Dosed by patient weight 0.5-2mg/kg.patient weight 0.5-2mg/kg.AEs: dryness of mucous membranes and skin, with AEs: dryness of mucous membranes and skin, with scaling, fragility, and erythema. Hair thinning. Increases scaling, fragility, and erythema. Hair thinning. Increases serum triglycerides. Muscle and joint pain. Visual serum triglycerides. Muscle and joint pain. Visual disturbances. Psychosis?disturbances. Psychosis?Known teratogen and abortifacient. Prescribers must Known teratogen and abortifacient. Prescribers must counsel patients of risks before prescribing. Females counsel patients of risks before prescribing. Females need negative pregnancy test, contraceptives starting need negative pregnancy test, contraceptives starting one month prior to start of isotretinoin, and taken for one one month prior to start of isotretinoin, and taken for one month after terminating drug. Prescriptions must have month after terminating drug. Prescriptions must have special sticker to be filled by pharmacist.special sticker to be filled by pharmacist.

Retinoid-Induced Retinoid-Induced TeratogenicityTeratogenicity

Retinoids Work by Initiating DNA Retinoids Work by Initiating DNA TranscriptionTranscription

Funny, He Doesn’t Look Like a Funny, He Doesn’t Look Like a NaziNazi

Dr. Albert Kligman, Dr. Albert Kligman, University of University of Pennsylvania, Professor Pennsylvania, Professor emeritus -- the father of emeritus -- the father of retinoid-based acne retinoid-based acne treatments.treatments.Conducted experiments Conducted experiments on prisoners at on prisoners at Holmesburg Prison Holmesburg Prison (Phildelphia) between (Phildelphia) between mid-50s to 1974.mid-50s to 1974.““All I saw before me were All I saw before me were acres of skin.” acres of skin.”

Percutaneous Absorption of DrugsPercutaneous Absorption of Drugs

Drug must be released from its vehicle if it is to Drug must be released from its vehicle if it is to exert and effect at the desired site of activity.exert and effect at the desired site of activity.Release of drug occurs at interface between skin Release of drug occurs at interface between skin surface and applied layer of product.surface and applied layer of product.Many physical-chemical factors determine Many physical-chemical factors determine relationship between the rate of absorption and relationship between the rate of absorption and the amount of drug released.the amount of drug released.The degree of skin hydration and thickness of The degree of skin hydration and thickness of applied layer of drug are also important. applied layer of drug are also important. Increased temperature at skin surface increases Increased temperature at skin surface increases blood flow to the area, and enhances rate of blood flow to the area, and enhances rate of percutaneous absorption.percutaneous absorption.

Percutaneous Absorption of Percutaneous Absorption of DrugsDrugs

Oily bases such as petrolatum are transiently occlusive, Oily bases such as petrolatum are transiently occlusive, promote hydration of the skin and generally increase promote hydration of the skin and generally increase molecular transport of drug. (ointments)molecular transport of drug. (ointments)Hydrous emulsions are less occlusive.Hydrous emulsions are less occlusive.Water-soluble bases (PEGs) are minimally occlusive, and Water-soluble bases (PEGs) are minimally occlusive, and may attract water from the stratum corneum and decrease may attract water from the stratum corneum and decrease drug transport. (solutions, gels, some creams)drug transport. (solutions, gels, some creams)Powders with hydrophilic ingredients presumably decrease Powders with hydrophilic ingredients presumably decrease skin hydration because they promote evaporation from skin by skin hydration because they promote evaporation from skin by absorbing available water.absorbing available water.Stratum corneum provides the greatest resistance to drug Stratum corneum provides the greatest resistance to drug absorption and is thought of as the rate-limiting step in absorption and is thought of as the rate-limiting step in percutaneous drug delivery. Molecular passage occurs percutaneous drug delivery. Molecular passage occurs mostly by passage diffusion.mostly by passage diffusion.Hydration swells the stratum corneum, loosening its normally Hydration swells the stratum corneum, loosening its normally tight, densely packed arrangement, thus making diffusion tight, densely packed arrangement, thus making diffusion easier.easier.

Dermatitis and Dry SkinDermatitis and Dry SkinDermatitis is a nonspecific term that describes a vast Dermatitis is a nonspecific term that describes a vast number of dermatological conditions that are number of dermatological conditions that are inflammatory and generally characterized by inflammatory and generally characterized by erythema. erythema. The terms dermatitis and eczema are often used The terms dermatitis and eczema are often used interchangeably to describe a group of inflammatory interchangeably to describe a group of inflammatory skin conditions of unknown cause.skin conditions of unknown cause.When the cause of a particular skin condition is When the cause of a particular skin condition is known, the disorder is given a specific name. Known known, the disorder is given a specific name. Known causes of dermatitis include allergens, irritants, and causes of dermatitis include allergens, irritants, and infections.infections.Dry skin (xerosis) is a common occurrence is almost Dry skin (xerosis) is a common occurrence is almost everyone. It may be seasonal in some, and chronic everyone. It may be seasonal in some, and chronic for others.for others.Often not serious, but annoying and uncomfortable Often not serious, but annoying and uncomfortable because of pruritis. Some may have pain and because of pruritis. Some may have pain and inflammation. Dry skin is more prone to bacterial inflammation. Dry skin is more prone to bacterial invasion than normal skin.invasion than normal skin.

Atopic DermatitisAtopic Dermatitis

Occurs most often in infants, children, and young adults. Occurs most often in infants, children, and young adults. Most common dermatological condition seen in young Most common dermatological condition seen in young children. In adults it is often associated with other skin children. In adults it is often associated with other skin conditions.conditions.Areas commonly affected (face, flexural areas on inside Areas commonly affected (face, flexural areas on inside of knees and elbows, and collar area of neck) depend on of knees and elbows, and collar area of neck) depend on the patient’s age.the patient’s age.““Atopy” means not in the right place. No diagnostic lab Atopy” means not in the right place. No diagnostic lab tests exist, though there may be elevated IgE and tests exist, though there may be elevated IgE and eosinophil levels.eosinophil levels.May be accompanied by allergic respiratory disease, but May be accompanied by allergic respiratory disease, but atopic dermatitis is often the initial clinical manifestation atopic dermatitis is often the initial clinical manifestation of an allergic disease.of an allergic disease.

Atopic DermatitisAtopic DermatitisCommon exacerbating factors include soaps, detergents, Common exacerbating factors include soaps, detergents, temperature changes, mold, dust, pollens, and emotional temperature changes, mold, dust, pollens, and emotional changes.changes.Thought to be genetically linked. 25% risk if one parent has it, > Thought to be genetically linked. 25% risk if one parent has it, > 50% if both parents have atopic dermatitis.50% if both parents have atopic dermatitis.Typically appears in the first year of life, as redness and Typically appears in the first year of life, as redness and chapping of the infant’s cheeks, which may continue to affect chapping of the infant’s cheeks, which may continue to affect the face, neck, and trunk. May progress to become more the face, neck, and trunk. May progress to become more generalized with crusting developing on the forehead or generalized with crusting developing on the forehead or cheeks. Result of dried exudate containing proteinaceous and cheeks. Result of dried exudate containing proteinaceous and cellular debris from erosion or ulceration of primary skin cellular debris from erosion or ulceration of primary skin lesions.lesions.Primary symptom is severely intense pruritic papules (solid, Primary symptom is severely intense pruritic papules (solid, round, and elevated lesions less than 1cm in diameter).round, and elevated lesions less than 1cm in diameter).Affected skin can progress to erythematous, excoriated, and Affected skin can progress to erythematous, excoriated, and scaling lesions. After repeated scratching and itching, the skin scaling lesions. After repeated scratching and itching, the skin becomes thick, or lichenified.becomes thick, or lichenified.

Atopic DermatitisAtopic Dermatitis

Source: dermatlas.med.jhmi.eduSource: dermatlas.med.jhmi.edu

Treatment of Atopic DermatitisTreatment of Atopic Dermatitis

Goals in treatment: 1. Maintain skin hydration, 2. Relieve Goals in treatment: 1. Maintain skin hydration, 2. Relieve or minimize symptoms of itching and weeping, 3. Avoid or minimize symptoms of itching and weeping, 3. Avoid or minimize factors that trigger or aggravate the disorder.or minimize factors that trigger or aggravate the disorder.Skin hydration through use of emolients and Skin hydration through use of emolients and moisturizers.moisturizers.Hydrocortisone can help prevent itching and weeping.Hydrocortisone can help prevent itching and weeping.See HCP if patient is less than 2 yr. old, or if condition is See HCP if patient is less than 2 yr. old, or if condition is severe or involves large area of body.severe or involves large area of body.

Contact DermatitisContact DermatitisRefers to a rash that results from an allergen or irritant in contact Refers to a rash that results from an allergen or irritant in contact with susceptible skin. Often the result of exposure to with susceptible skin. Often the result of exposure to occupational irritants.occupational irritants.Usually occurs in children over 8yr old.Usually occurs in children over 8yr old.Irritant contact dermatitis is nonallergic and nonimmunologic Irritant contact dermatitis is nonallergic and nonimmunologic reaction caused by exposure to irritating substances. Often reaction caused by exposure to irritating substances. Often occupation-related and commonly seen in patients who work in occupation-related and commonly seen in patients who work in food, plastics, oil, agriculture, or construction industries.food, plastics, oil, agriculture, or construction industries.Irritant generally elicits a response on first exposure. Injury it Irritant generally elicits a response on first exposure. Injury it causes to the skin may not be limited to erythema and causes to the skin may not be limited to erythema and vesiculation, but may result in ulceration and tissue necrosis. vesiculation, but may result in ulceration and tissue necrosis. Mild irritants generally require repeated or extended contact to Mild irritants generally require repeated or extended contact to cause a significant inflammatory response.cause a significant inflammatory response.Acute irritation is more likely if the area is under occlusion, which Acute irritation is more likely if the area is under occlusion, which minimizes evaporation and causes the skin to become more minimizes evaporation and causes the skin to become more permeable to chemicals. Gloves, clothing, and diapers often permeable to chemicals. Gloves, clothing, and diapers often increase susceptibility and should be changed often. increase susceptibility and should be changed often.

Contact DermatitisContact Dermatitis

Some agents may act as sensitizers: iodine containing Some agents may act as sensitizers: iodine containing antiseptics, latex, formaldehyde, benzocaine, PABA, topical antiseptics, latex, formaldehyde, benzocaine, PABA, topical diphenhydramine (Benadryl®).diphenhydramine (Benadryl®).Allergic contact dermatitis is immunologically mediated and is Allergic contact dermatitis is immunologically mediated and is manifested by a delayed-hypersensitivity reaction to contact manifested by a delayed-hypersensitivity reaction to contact allergens. Involves contact of the skin with an allergenic material allergens. Involves contact of the skin with an allergenic material acting as a hapten, which becomes attached to protein carriers acting as a hapten, which becomes attached to protein carriers on specific cells in the epidermis. Initial sensitizing exposure is on specific cells in the epidermis. Initial sensitizing exposure is necessary for the reaction to occur. On subsequent contact with necessary for the reaction to occur. On subsequent contact with the allergen, reactive skin areas typically present as eczema – the allergen, reactive skin areas typically present as eczema – appearing within minutes to hours after exposure. Example: appearing within minutes to hours after exposure. Example: poison ivy.poison ivy.Hands are most often involved in adults, particularly on the Hands are most often involved in adults, particularly on the backs of the hands. Can occur on the upper back, thighs, backs of the hands. Can occur on the upper back, thighs, axillary areas, feet, and face. Lesions are often asymmetric and axillary areas, feet, and face. Lesions are often asymmetric and well-defined, reflecting where contact with the substance well-defined, reflecting where contact with the substance occurred.occurred.

Contact Dermatitis from Contact Dermatitis from ShoesShoes

Source: dermatlas.med.jhmi.eduSource: dermatlas.med.jhmi.edu

Treatment of Contact DermatitisTreatment of Contact Dermatitis

Decreasing exposure to irritants such as detergents, Decreasing exposure to irritants such as detergents, soaps, and solvents is a good preventative measure.soaps, and solvents is a good preventative measure.Mild-to-moderate contact dermatitis usually amenable to Mild-to-moderate contact dermatitis usually amenable to treatment with nonprescription agents. Astringents such treatment with nonprescription agents. Astringents such as aluminum acetate can dry lesions (Apply 20min, 4 as aluminum acetate can dry lesions (Apply 20min, 4 times a day). Calamine and colloidal oatmeal can relieve times a day). Calamine and colloidal oatmeal can relieve itching. Hydrocortisone reduces erythema. Systemic itching. Hydrocortisone reduces erythema. Systemic antihistamines such as diphenhydramine and antihistamines such as diphenhydramine and chlorpheniramine may relieve itching and help with chlorpheniramine may relieve itching and help with sleep.sleep.Duration of therapy is usually short because the Duration of therapy is usually short because the condition usually improves upon withdrawal of the condition usually improves upon withdrawal of the allergen or irritant, typically within hours.allergen or irritant, typically within hours.

Products for Atopic Dermatitis, Products for Atopic Dermatitis, Contact Dermatitis, and Dry SkinContact Dermatitis, and Dry Skin

Bath oils consist of a mineral or vegetable oil, plus a Bath oils consist of a mineral or vegetable oil, plus a surfactant. Mineral oil is better adsorbed on the skin surfactant. Mineral oil is better adsorbed on the skin than vegetable oil. than vegetable oil. Only minimally effective in improving dry skin Only minimally effective in improving dry skin because they are greatly diluted in water. Effect may because they are greatly diluted in water. Effect may be enhanced by adding oil at end of bath, and be enhanced by adding oil at end of bath, and patting skin dry instead of rubbing it. patting skin dry instead of rubbing it. Make tub and floor slippery, creating a safety Make tub and floor slippery, creating a safety hazzard especially for the elderlyor children.hazzard especially for the elderlyor children.Make cleansing the skin with soaps more difficult.Make cleansing the skin with soaps more difficult.Colloidal oatmeal bath products (Aveeno®) contain Colloidal oatmeal bath products (Aveeno®) contain starch, protein, and a small amount of oil. Less starch, protein, and a small amount of oil. Less effective at moisturizing than bath oils, but have effective at moisturizing than bath oils, but have antipruritic effect. May clog bath pipes if used on a antipruritic effect. May clog bath pipes if used on a regular basis.regular basis.

Emollients/MoisturizersEmollients/MoisturizersMost commonly used emollients include petrolatum Most commonly used emollients include petrolatum and mineral oil. Attempt to formulate products that and mineral oil. Attempt to formulate products that try to function like sebum. Sometimes try to use try to function like sebum. Sometimes try to use exotic oils to mimic lipid content, but petrolatum exotic oils to mimic lipid content, but petrolatum works best.works best.Emollients are occlusive agents and moisturizers that Emollients are occlusive agents and moisturizers that are used to prevent or relieve the signs and are used to prevent or relieve the signs and symptoms of dry skin. Act by leaving an oily film symptoms of dry skin. Act by leaving an oily film behind on skin surface through which moisture can behind on skin surface through which moisture can not readily escape.not readily escape.Some HCPs believe that emollients alone are not Some HCPs believe that emollients alone are not enough to maintain adequate skin hydration. A enough to maintain adequate skin hydration. A patient may be advised to hydrate the skin by patient may be advised to hydrate the skin by soaking in water for 5-10 minutes, patting the skin soaking in water for 5-10 minutes, patting the skin dry, and applying an occlusive agent while the skin is dry, and applying an occlusive agent while the skin is still damp. Drinking plenty of water should also be still damp. Drinking plenty of water should also be stressed.stressed.

HumectantsHumectants

Humectants are hydrating agents that attract water. Humectants are hydrating agents that attract water. Often added to emollient base to draw water into the Often added to emollient base to draw water into the skin. Used alone they can evaporate water out of skin. Used alone they can evaporate water out of stratum corneum.stratum corneum.

Examples are glycerin, propylene glycol, and Examples are glycerin, propylene glycol, and phospholipid products like lecithin.phospholipid products like lecithin.

Keratin-Softening AgentsKeratin-Softening Agents

Chemically alter the keratin layer to soften skin and Chemically alter the keratin layer to soften skin and cosmetically improve its appearance. Dry skin cosmetically improve its appearance. Dry skin symptoms will not be improved without adding water symptoms will not be improved without adding water to the stratum corneum.to the stratum corneum.Urea in concentrations of 10-30% is mildly keratolytic Urea in concentrations of 10-30% is mildly keratolytic and increases water uptake into the stratum corneum. and increases water uptake into the stratum corneum. Is able to remove crusted necrotic tissue at higher Is able to remove crusted necrotic tissue at higher concentrations, however causes stinging, burning and concentrations, however causes stinging, burning and irritation particularly on broken skin.irritation particularly on broken skin.Lactic acid is useful for treating dry skin at Lactic acid is useful for treating dry skin at concentrations of 2-5%. Increases hydration of concentrations of 2-5%. Increases hydration of human skin, and acts as a modulator of keratinization human skin, and acts as a modulator of keratinization rather than a keratinolytic agent. Added to urea to rather than a keratinolytic agent. Added to urea to stabilize effects on skin and for hydration.stabilize effects on skin and for hydration.Allantoin is also a keratin softening agent, works by Allantoin is also a keratin softening agent, works by disrupting the structure. Generally less effective than disrupting the structure. Generally less effective than urea for softening skin.urea for softening skin.

AstringentsAstringents

Retard oozing, discharge, or bleeding of dermatitis when Retard oozing, discharge, or bleeding of dermatitis when applied to unhealthy skin or mucous membranes. Work applied to unhealthy skin or mucous membranes. Work by coagulating proteins.by coagulating proteins.When applied as a wet dressing or compress, they cool When applied as a wet dressing or compress, they cool and dry the skin through evaporation. Act as and dry the skin through evaporation. Act as vasoconstrictors and reduced blood flow to inflamed vasoconstrictors and reduced blood flow to inflamed tissue, and cleanse the skin of exudates, crust, and tissue, and cleanse the skin of exudates, crust, and debris. Have a low cell permeability so activity is limited debris. Have a low cell permeability so activity is limited to the cell surface and interstitial spaces.to the cell surface and interstitial spaces.Examples are aluminum acetate and witch hazel. Examples are aluminum acetate and witch hazel. Patient may soak affected area in astringent solution two Patient may soak affected area in astringent solution two to four times daily for 15 to 30 minutes.to four times daily for 15 to 30 minutes.

Topical HydrocortisoneTopical Hydrocortisone

Only corticosteroid available without a prescription for Only corticosteroid available without a prescription for topical treatment of dermatitis. Available 0.5%, 1% topical treatment of dermatitis. Available 0.5%, 1% creams, ointments, sprays.creams, ointments, sprays.Exact mechanism of action is unknown, it relieves Exact mechanism of action is unknown, it relieves redness, heat, pain, swelling, and itch associated with redness, heat, pain, swelling, and itch associated with many dermatoses, possibly due to a vasoconstrictive many dermatoses, possibly due to a vasoconstrictive effect.effect.Apply sparingly to affected area three to four times a Apply sparingly to affected area three to four times a day. Make sure that infection is not present (bacterial or day. Make sure that infection is not present (bacterial or fungal), HC masks the signs of infection, allowing it to fungal), HC masks the signs of infection, allowing it to progress without patient knowing. Ask pharmacist if you progress without patient knowing. Ask pharmacist if you are unsure.are unsure.Do not use for prolonged periods of time. Response Do not use for prolonged periods of time. Response decreases over time, and skin atrophy may occur decreases over time, and skin atrophy may occur because of inhibited collagen production.because of inhibited collagen production.

QUESTIONS?QUESTIONS?

tafkab@u.washington.edu tafkab@u.washington.edu