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Xerosis, or dry skin, is a condition that is characterized by rough, dry and scaly skin (Table 1).

1 Dry skin is a common condition that impacts patients' level of discomfort, and ultimately quality of life.2 Patients may experience symptoms of itching, tightness, pain, tingling, or stinging. Many times, dry skin is the manifestation of an underlying skin disorder, such as atopic dermatitis or psoriasis. Almost all patients will experience a component of dry skin at some point in their lives; however, the prevalence increases with age.3 Table 1. Signs and Symptoms of Dry Skin Adapted from reference 9. Dry, white patches Fissures Flaky appearance Lack of luster Redness Rough Uncomfortable feeling (pain, itchy, stinging, tingling) Uneven The American Academy of Dermatologists recommends a daily routine for general skin care. This routine includes cleansing, moisturizing, and using sunscreen.4 This will help prevent the condition or at least decrease the damage to skin. Patients often need to be prompted and reminded to follow these basic techniques, which often times alone are sufficient in keeping skin well hydrated. One complication of dry skin is fissures, which occur most commonly on the lower leg region. Sometimes, fissures can be so severe that they affect the deep dermal capillaries and cause bleeding in some patients.5 Dry skin has a prevalence as high as 85% in the elderly population, with almost all patients being affected to some degree by the age of 70 years.6,7 Often referred to as the "winter itch," this condition may be aggravated by the colder weather, low humidity, indoor heating, soaps, and cleansers.1,7-8 The "winter itch" take approximately 3 to 4 weeks to develop after the onset of cold weather and then 3 to 4 weeks to resolve as the weather gets warmer.9 This is an important finding when gathering information about the history of a patient's dry skin. Pruritus, or itching, is a widespread problem and a complication of dry skin among patients. Whereas dry skin is the most common cause, there are underlying diseases that could contribute to the development of pruritus.10-11These conditions include leukemia, anemia, AIDS, renal failure, obstructive jaundice, hypo- or hyperthyroidism, lymphoma, and diabetes mellitus.12-14 In patients with presentation of generalized itching, therefore, it may be worthwhile to work up the patient for an underlying condition. At the minimum, a complete blood count, urinanalysis, thyroid function test, and renal function test should be investigated.13,15 Many medications can induce pruritus without any visible lesions,10 therefore, an extensive medication review by the pharmacist is invaluable in the patient workup. Depending on the offending agent, a decision can be made on how necessary the offending agent is to continue. Structure of the Skin The skin is divided into 3 main tissue areas or layers-the hypodermis, the dermis, and the epidermis. The hypodermis is loose connective tissue where formation and storage of fat occurs. Deep-rooted hair follicles and sweat glands also originate here. The fatty layer acts as a thermal regulator, food control, and

cushioning. The hypodermis plays an integral role in supporting blood vessels and nerves that travel to and through the dermis.16 The dermis is a layer of connective tissue rich in blood and nerve supply. The dermis has internal layers, the papillary (connects dermis to epidermis) and reticular sublayers (connects dermis to hypodermis). Thickness of the dermis varies from area to area, being the thickest on the back and thinnest on the eyelids. Its main function is to offer support to the skin and its annexes, such as hair and nails.16 The epidermis is the outermost layer and is perhaps of the utmost importance. The layers of the epidermis include the stratum germinativum (basale), stratum spinosum (prickle), stratum granulosum (granular), stratum lucidum (lucid, only present in thick-skinned areas such as palms and soles), and stratum corneum (SC; horny). Each layer has proliferated keratinocytes that travel upwards while cornification occurs. Cornification is the process of forming an epidermal barrier in stratified squamous epithelial tissue (Figure 1). As they move to the top and reach the final layer, the keratinocytes flatten, lose their nuclei, and fill with keratin fibers.9,16-17 The dead keratinocytes are now corneocytes. Eventually, corneocytes are shed. In healthy skin, this process of epidermal differentiation takes approximately 14 days.17

Figure 1: Skin Structure in Normal vs Dry Skin Intracellular lipids stabilize corneocytes in a wall-like structure. Lipids also move upwards from lower epidermis levels and play a vital role in retaining water in the body. They are converted from phospholipids to nonpolar lipids (ceramides, free sterols, free fatty acids, and cholesterol) by enzymes along the way.18,19 These intercorneocyte lipids are arranged in layers and are important for cellular cohesion. They play an important role in the keratinization process and the moisturization of the skin. Any disruption in structure can cause moderate to severe dry skin.20 Major functions of the skin are to protect the body from physical and chemical harm and to prevent loss of body water and other substances. The protein-enriched corneocytes and lipid-enriched intracellular domains establish the function of the SC, as they literally form a barrier between the interior body and external world.21,22 The function of the SC is maintained by water, which ensures that the SC is soft and flexible. If water is lost and skin is dry, the SC becomes hard and brittle, losing its ability to function and clinically presenting with irritating symptoms.

Low molecular humectants called natural moisturizing factor (NMF) are contained within the corneocytes. They are water soluble and account for 15% to 20 % of the SC.23,24 NMFs play a crucial role in the water holding capacity of the skin and increase its elasticity as well. Without NMFs, the skin's water binding capacity is lost or diminished.24,25 Water is also necessary to maintain metabolic processes of the skin.26 Causes of dry skin may be due to many culprits (Table 2). Dry skin is related to decreased water retention rather than low natural oils.27 Low NMFs and high transepidermal water loss (TEWL) are among many causes of dry skin. Low levels of sodium, chloride, lactate, and potassium have been shown to have an association with dry skin.28 Environmental triggers including low humidity and cold weather have also been linked to low skin hydration. Exposure to cigarette smoke and constant contact with skin irritants may cause a disruption in the lipid barrier in the SC. Also, abrasion and friction from clothing may contribute to dry skin. They could physically disrupt the lipid barrier, leading to dry skin.9 Pharmacist should be sure to ask about these potential causes to ensure that the underlying problem is addressed during treatment.

Table 2. Causes of Dry Skin Adapted from reference 31. Cigarette smoke exposure Cool, air conditioned surrounding, cold weather Disturbed epidermal differentiation Exposures to chemicals Frequent showers Friction Ultraviolet radiation Warm, heated surroundings, hot, dry weather Differential Diagnosis Other skin conditions that have a component of dry skin include atopic dermatitis, psoriasis, and seborrheic dermatitis. Atopic dermatitis (AD), better known as eczema, is a chronic disorder that involves inflammation of the skin and commonly presents as an intense itching sensation. Many times patients do not see lesions and describe the condition as an "itch that became a rash." Prevalence of AD is more common in children (15%-30%) that adults (2%-10%).29 When AD coexists with both asthma and allergic rhinitis, together the 3 are called the atopic triad. Clinical presentation of AD differs by age. In infants, an erythematous papular rash can be seen on the cheeks, chin, forehead, scalp, and behind the ears. As a patient grows, the rash typically presents in flexor areas, where skin touches skin. Behind the knees, inside the elbow crease, and on eyelids are a few examples. The rash is often brought on by triggers that may include food, environmental factors, or even emotions, namely stress. Treatment for AD, in part, is focused on the same treatments as dry skin because it is such a large component of AD. Nonpharmacologic and some pharmacologic treatments are identical and necessary. AD typically requires more aggressive pharmacologic treatment with steroids and other antipruritic agents. Pharmacists should reinforce the self-care routines that patients with AD must follow. They are necessary to prevent flare-ups of the disease.29 Seborrheic dermatitis (SD) is a chronic skin disorder with characteristics of inflammation, erythema, and scaling eruptions. It is commonly seen in 2 populations, infants (younger than 1 year old) and adolescents/young adults (puberty). Throughout adulthood, SD follows an on/off pattern. In infants, SD is

referred to as cradle cap and presents as red, flaky, inflamed scales covering the scalp. In the young adult population, the same presentation occurs, but in the areas of the scalp, hairline, eyelid margins, nasolabial folds, beard area, and external ear canal. Severity of the disease can vary greatly from person to person. Mainstay of treatment for SD is antifungals, corticosteroids, and dandruff shampoo. Moisturizers may play a role in maintaining normal skin between eruptions of SD.29 Psoriasis is a disease that can be recognized by specific lesion type. Psoriatic lesions may be due to genetic or environmental factors and most patients have an onset of the disease before age 40 years. Throughout life, a patient's psoriasis will wax and wane. Patients must learn to recognize what factors contribute to flare-ups of their lesions. Pharmacist should pay close attention to other medications a patient may be taking because they may contribute to a lesion flare. Psoriatic plaques are very distinct. The edges are erythematous and red/violet in color with well demarcated borders that are clearly distinguished from normal skin. The center of the lesion is covered by silver plaques. The lesions may present anywhere on the body, depending on the patient, however are mostly commonly seen on the outer area just above the elbows and below the knees. The extent of treatment depends on the percentage of body surface area affected. Topical agents are used in mild cases as well as on localized areas in moderate to severe cases. The mainstay of therapy is corticosteroids. Vehicle choice, or base, for the therapeutic agent to be administered is a very important part of therapy as well, and mirrors choices one would make when treating patients with dry skin. As psoriasis becomes more severe, therapy becomes more intense with oral agents. It is important for patients to keep up with skin moisturizing during and between flare-ups, as this will help minimize symptoms as well as complications. Pharmacists are in an ideal position to educate patients on keeping skin well hydrated during flare-ups.16,29 Skin in the Elderly30 Skin is one of the many organs that are affected by change. The components of change are both intrinsic, meaning structural and functional disturbances, as well as extrinsic, meaning the history of years of exposure to many environmental factors. Many dermatologic autoimmune diseases present as a patient's age increases. Physiologic and pathologic changes in the skin result in clinically significant presentation in patients as well (Table 3). Polypharmacy also increases the presence of cutaneous manifestation, including dry skin, in the older population. Prevalence of polypharmacy increases with age and this may not only induce a dry skin condition, but other drug reactions with cutaneous manifestations. Pharmacists have an important opportunity to intervene to ensure that medication use is appropriate and to recommend changing or discontinuating a therapy when appropriate. Table 3. Changes in Skin with Increased Age Leading to Dry Skin30,34-36 Physiologic change Atropy of sweat glands Reduced movement of water from dermis to epidermis Reduced stratum corneum lipids Pathologic change Decreased sweating Reduced epidermal hydration Decreased ability to retain water

As skin ages, collagen and elastin fibers decrease as along with total skin thickness.31 A direct result of the decreased thickness is a decrease in water and lipid content, sebum production, and sweating, naturally resulting in dryer skin.5 These degenerative changes result in a change of structure and begin to affect the dermal vasculature.32 Pressure ulcers and dermatitis are among many conditions that presently heavily in the elderly.1,33

Management of Dry Skin Management of dry skin should always include nonpharmacologic treatments, and pharmacologic treatments should be considered only if necessary.27 It is important to understand the different ingredients in skin products meant for moisturizing. The term moisturizer is often used interchangeably with emollient. Emollients are an important component of moisturizers that should be present in order to be effective.21 Modification to bathing practices is an important nonpharmacologic treatment for patients with dry skin.27 Pharmacists should ask about bathing practices to see if this could potentially be part of the cause of the problem. Patients with dry skin should be taking tub baths 2 to 3 times per week in tepid water, no warmer than approximately 90F. Total time in water should be approximately 3 to 5 minutes. If desired, bath oil may be added to bath water towards the end of the bath to help increase skin hydration. After exiting the bath, patient should pat the skin dry and apply moisturizer within 3 minutes. Moisturizer should be applied generously and may be continued throughout the day.27 This technique will lock water into the skin. Additional nonpharmcologic strategies to manage dry skin include increasing the air humidity. This may be achieved with a humidifier or vaporizer. This may be necessary all year long, depending on the patient. Proper care technique should be emphasized to keep the device clean and mildew-free. Furthermore, encourage the patient to drink water, up to 8 glasses a day, for increased overall hydration.27 The base or vehicle of topical formulations has therapeutic properties and the proper choice is important for treatment (Table 4). Creams, ointments, gels, pastes and liquid preparations are among the many available choices from which patients and clinicians can choose.21 The choice of the base may depend on where the product is meant to be applied. Body moisturizers are most commonly lotion based and provide easily spreadable product, especially in hair-bearing areas.27

Table 4. Important Components of Moisturizers to Treat Dry Skin 9 Lipids (mineral, vegetable oil) Physiological lipids (ceramides, cholesterol) Humectants (glycerol, AHAs) Antipruritics Cell/lipid metabolism support Substitutes natural skin lipids lost Aids in epidermal differentiation Increases water content in SC and has barrier function Breaks the itch-scratch cycle Aids in epidermal differentiation, fibroblast proliferation, protein & lipid synthesis

Moisturizers generally consist of 60% to 80% water, lipids, emulsifiers, humectants, preservatives, fragrance, color, and possibly special additives, such as vitamins and NMFs. It should be noted that vitamins add no potential benefit when applied topically. Topical products mostly differ by the addition of different fragrances, color, and special additives. The role of lipids in moisturizers is to provide occlusion, reducing the loss of water from the skin. Most moisturizers are either water-in-oil (W/O) or oil-in-water (O/W) emulsions. O/W emulsions have an oil content that can vary by 15% to 30%. They tend to be greasier than W/O emulsions and more resistant to washing off after application.37 W/O emulsions have a higher lipid content that results in occlusive

properties. Most patients prefer O/W preparations, as they are more esthetically acceptable, spreading more easily and absorbing more quickly into the skin.27 Common oil or lipid materials found in moisturizers include mono-, di- and triglycerides, waxes, esters, petrolatum, fatty acids, lanolin, and mineral oils. Often, lipid-based products are recommended to form an occlusive layer to reduce TEWL.9 Humectants are among the most important properties in choosing a topical product. It is important that a product contain humectants in order to really hydrate the SC.21 These are components that are added to an emollient base to increase the water binding capacity and affect the degree of skin hydration.24,27 Humectants hydrate the skin by drawing water into the SC either from the dermis or the atmosphere. Humidity must be at least 80% for water to be drawn in from the atmosphere. At lower concentrations, humectants may also decrease water loss from the body.27 Alpha-hydroxy acids (AHAs) are a group of humectants that consist of lactic acid, glycolic acid and tartaric acid. Lactic acid is the most commonly used AHA within this group due to its buffering properties and water binding capacity. Ranges of up to 12% lactic acid have been used in the treatment of dry skin.28 Urea is a keratolytic that increases the water-binding capacity of the SC. It binds to skin proteins in the SC allowing for increased elasticity of the skin. Concentrations of 10% may be used on mild dry skin, but formulations of up to 30% have been used on more severe or resistant dry skin.27 Topical lotions and creams containing urea may be beneficial in removing crust lesions and scales, whereas urea based in emollient ointments are better at rehydrating the skin. Common adverse events that patients may experience include mild stinging or burning, especially where skin is broken.27 Counseling patients to start with a small amount of the product and work up to larger amounts may minimize adverse events when using a urea-based product. Glycerin (or glycerol) is a commonly used humectant with smoothing properties, making it an important component of many moisturizers. In dry skin, the amount of lipids in solid state is increased. Glycerin helps to prevent the crystallization of lipids at low humidities, thereby helping to treat dry skin by maintaining lipids in liquid crystalline.39 Normal water content of the skin is 15% to 20%.40 Propylene glycol (PG) is an alcohol humectant and is often referred to as a penetration enhancer. PG attracts water and is many times added into cosmetics and pharmaceuticals to stabilize substances that are unstable in water.41 In skin that is seriously damaged and dry, to the point where there is cracking and potentially even bleeding, an astringent may be considered for short-term use. Astringents, such as aluminum acetate (Burrow's solution) or witch hazel, will reduce oozing or bleeding in damaged areas of the skin. Astringents cause vasoconstriction, thereby reducing the blood flow to the underlying tissue. A dilution of 1:10 to 1:40 solution (astringent: water) can be made and the area may be soaked the 2 to 4 times a day for 15 to 30 minutes. Alternatively, the patient may apply the solution using clean washcloth dipped in the diluted solution and wrung out so it is not dripping. Patients may apply the cloth 4 to 6 times day for 20 to 30 minutes, changing the cloth every few minutes.27 The use of astringents in patients with dry skin should be done very consciously. Overuse will dry skin out even further. This technique may be useful when a patient is looking to clear up a crusty lesion quickly. Patients should not use astringents for more than 3 days at a time. This should be followed by an intense moisturizing routine. Antihistamines should be reserved for a last option for treating pruritis associated with dry skin. Pharmacists should ensure that other nonpharmacologic and pharmacologic topical treatment have been instilled before recommending oral anithistamines. This is to avoid unnecessary medication use by the patient. If an oral antihistamine is used, a second-generation or less sedating first-generation option would be best. Patients should be counseled that it may take a few days for the itching to subside. If the pruritis is an extreme annoyance to the patient upon diagnosis of dry skin, adding the oral agent and topical agents at the same time may be considered, with intentions of discontinuing the oral antihistamine within a short timeframe. Uses of topical corticosteroids have a limited role in treatment of dry skin. They may have a place in therapy indirectly by being used for their anti-itch properties and stopping the itch-scratch cycle, but they do not play a role in treatment of the underlying cause. The long-term effects of topical corticosteroids are undesirable as

well. Atrophy of the skin and straie are among the effects seen after prolonged use.9 It is better to treat the underlying dry skin condition with an appropriate moisturizer rather than get a quick fix with a topical corticosteroid. If used, therapy should only be for a short period of time (less than 1 week) and the focus should be on moisturizing the skin appropriately.9 Role of the Pharmacist The pharmacist's role in the management of generalized dry skin begins with retrieving a thorough background of the patient. A detailed medication history is a critical part of the evaluation to identify any medications or personal habits that may be contributing to the patient's dry skin symptoms or exacerbating any underlying conditions. This history should include not only prescription medications but nonprescription medications as well, including supplements of any sort, vitamins, and herbal products. It would be wise to gather a history about what products the patient has used on his or her skin, as well as the technique used when applying the product. Compliance can be a challenge in treatment of dry skin because the frequency of application for moisturizers should be 3 to 4 times a day. Many times, patients use worthwhile products inappropriately. Pharmacists should instruct patients to use proper application techniques and follow instructions carefully. The overwhelming amount of products available for patients' self-care may lead to a poor choice of product. Pharmacists should direct patients to a moisturizer that will make more of an impact on treating their dry skin condition. Bathing habits should be discussed with patients and should include instructions on proper techniques in regards to the application of moisturizing agents after cleansing, which is to apply moisturizer within 3 minutes of bathing to ensure that water is locked in the skin. Emphasizing continuity of care is also important. As patients' skin becomes better, compliance with moisturizers may decrease, resulting in a relapse of dry skin. Patients should be educated that continuation of their moisturizer is important for the future prevention of their dry skin condition. Choice of delivery system or vehicle base is an important intervention pharmacists can discuss with their patients. The pros and cons of vehicle base should be discussed with patients, who then can choose their options based on their new knowledge. This may lead to greater compliance because the patient knows what to expect from the moisturizer. Greasiness, stickiness, smoothness, and smell of some products may be a deterrent and lead to noncompliance. Creams generally are the most well accepted vehicle. Conclusion The ideal moisturizer should contain ingredients that will address deficiencies within the skin, as discussed above. It should protect skin from further damage while adding back to the skin what it is lacking. This does not always mean just adding water. Selecting the correct moisturizer and using it correctly are keys to the successful and appropriate management of dry skin. Pairing these two concepts should result in optimal outcomes. Pharmacists are in primary role in aiding patients in both these opportunities. Patients often seek self-care of dry skin management, and pharmacists are at the frontline to help.
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