Topical therapy has always played a large role in dermatology because of the obvious access to the affected tissue.^4,^17,⁴⁴ Topical applications continue to be popular and useful in treating equine skin disease. Growth in topical therapy reflects multiple factors, which may include: (1) the development of more products, better delivery systems, and active ingredients; (2) the reduction in systemic absorption or effects and adverse reactions; and (3) the recognition of the adjunctive and synergistic effects in the overall management of numerous skin diseases. These factors are also the advantages that topical therapy offers to the clinician and the horse owner.

However, this therapy also entails some disadvantages. In general, topical therapy is much more time-consuming and labor-intensive than systemic therapy. Understanding the proper use and application of topical therapy is also important, and therefore client education and compliance become more difficult to achieve. Localized adverse reactions not seen with systemic therapy may occur, most commonly irritant reactions.

Topical products commonly used for the treatment of equine dermatoses have received little or no scientific investigation. Hence, many treatment protocols are based on anecdotal reports or have been extrapolated from other species. Companion animal products are frequently used on horses and are safe and effective.^30,⁴⁴

Topical therapy is often adjunctive, and it may significantly increase the cost of the overall therapeutic plan. Some topical agents may be so costly that their use is limited to localized lesions. On the other hand, appropriate topical therapy may greatly reduce the need for systemic therapy. The clinician needs to consider the potential benefits and disadvantages, the client’s preferences, and the patient’s needs when deciding on the use of topical therapy.

When a clinician elects to use topical therapy, several factors must be considered. Primarily is, what is the purpose or desired result of the topical therapy? Is this the sole therapy, or is it adjunctive to other nontopical therapies? What type of delivery system best facilitates obtaining the desired result? What active ingredients are used for this purpose? As previously discussed, patient and client considerations are paramount. Table 3-1 lists the most common delivery systems and formulations of active ingredients used in veterinary dermatology. The amount of use for each type of product relative to the others is based solely on the authors’ opinions and clinical impressions.

TABLE 3-1 Topical Formulations and Relative Efficacy of Incorporated Active Agents*

Factors That Influence Drug Effects on the Skin

Topical medications consist of active ingredients incorporated in a vehicle that facilitates application to the skin. In selecting a vehicle, one must consider the solubility of the drug in the vehicle, the rate of release from the vehicle, the ability of the vehicle to hydrate the stratum corneum, the stability of the active agent in the vehicle, and the interactions (chemical and physical) among the vehicle, the active agent, and the stratum corneum. The vehicle is not always inert and many have important therapeutic effects.

When topical medications are used, one basic question is whether the drug penetrates the skin and, if so, how deeply. Absorption varies highly, and most drugs penetrate only 1-2% after 16-24 h. However, even in the same vehicle, similar drugs may vary dramatically in their absorption. In some cases (e.g., insecticides), the absorbability greatly influences the potential for side effects.

Clinical efficacy and absorption are not synonymous; absorption is only one factor in efficacy. Some drugs in an insoluble form in the vehicle have only a surface effect. Once absorbed, a drug must also interact with specific receptors before an action will result. The drug’s affinity for the receptors and local factors that affect this drug-receptor interaction are also important. Absorption of drugs through the skin involves many variables. There are physicochemical factors related to the topical formulation and biologic factors. The physicochemical factors involve the interactions between the drug and the vehicle, the drug and the skin, and the vehicle and the skin. Some of these factors are determined by the concentration of the drug, the drug’s movement between the vehicle and the skin, the diffusion coefficient, and the local pH.^17,^26,⁴⁴

1. The concentration of the drug and its solubility in the vehicle affects absorption. The package label gives the percentage of drug concentration, not the percentage of solubility. In addition to concentration, the solubility of the drug and the solubilizing capacity of the vehicle affect drug absorption. In general, poor solubility and excessive solubilizing capacity decrease the rate of absorption. Usually, ointment vehicles for topical corticosteroids increase solubility and drug delivery, so systemic effects after topical use are more common—and potentially dangerous.

2. The drug must move from the vehicle through the skin barrier to be effective. The solubility of the drug in the horny layer relative to its solubility in the vehicle is described by the partition coefficient. The concentration of the drug in the barrier, not in the vehicle, is what determines the diffusion force. Increased lipid solubility favors drug penetration because the stratum corneum is lipophilic.

3. The diffusion coefficient is a measure of the extent to which the barrier interferes with the drug’s mobility. The stratum corneum is unsurpassed as an unfavorable environment for drug penetration. Physical disruption of the epidermal barrier by the use of lipid solvents, keratolytic agents, or cellulose-tape stripping of the top layers of cells increases the potential for absorption. In some cases, the vehicle itself may be able to diffuse through the stratum corneum and carries any dissolved drug with it. DMSO facilitates cutaneous penetration of some substances. Moisture and occlusive dressings enhance percutaneous absorption as well. Large molecular size results in poor mobility and poor absorption.

4. The pH of the drug’s local environment may also affect absorption by altering the amount of drug in its unionized form. Many drugs are either weak acids or bases and occur in an ionized and unionized form. In general, the unionized form is more readily absorbed; this amount may change as the local pH is altered.

The active ingredient of the drug may interact with all other components in the formulation. In practice, the addition of other ingredients or the mixing of ingredients on the skin may alter the drug’s effect. Drug effects may be altered by interactions between the drug and the new drug or its vehicle, or by interactions between the new drug or vehicle and the original vehicle. Changes that may occur include inactivation of the drug by chemical bonding or precipitation, changes in pH, allowing decomposition of the drugs by altering the stabilizing effects of the vehicle, and altering the concentration of the drug.

Temperature and hydration of the skin can affect the interaction among the drug, the vehicle, and the skin. Hydration probably plays a greater role than temperature in affecting absorption. In general, permeability to drugs increases as the hydration of the stratum corneum increases.

Biologic factors also affect drug absorption. The body region treated may influence absorption. In horses, topical hydrocortisone penetrates faster through lower leg skin than through skin of the thorax or groin.²⁷ Age is an important factor, with newborns experiencing greater absorption than adolescents do, who in turn experience greater absorption than adults do. Obviously, the health and condition of the skin is important because inflamed, abraded, or otherwise damaged skin often absorbs more drug. Blood flow also affects absorption. Greater blood flow favors increased systemic absorption.

Hydrotherapy

Water is often overlooked as a therapeutic agent, especially when it is applied with a shampoo, as a rinse, or as a component of many lotions. Hydrotherapy may be used to moisten the stratum corneum, to dry out the epidermis, to cool or heat the skin, to soften surface crusts, and to clean the skin. Increased effects occur by the addition of other agents.

Water may be applied as a wet dressing or in baths. Frequent periodic renewal of wet dressings (15 min on, several hours off) prolongs the effect, but if more continuous therapy or occlusive coverings are used, the skin becomes overly moistened, the skin temperature rises, and undesirable maceration occurs. This is less likely if the wet dressings are left open.

Hydrotherapy can hydrate or dehydrate the skin, depending on how it is managed. The application of loose, damp gauze compresses for 15 min followed by their removal for 1 h promotes evaporation of water from the gauze and from the subadjacent skin surface and is drying to the underlying tissues. If water is maintained on the skin surface constantly by wet towels, saturated disposable baby diapers, soaks, or baths, the skin hydrates as water is taken up by keratin and hair. If a film of oil is applied immediately after soaking (occlusive rinses), evaporation of water (transpiration) is hindered and the skin retains moisture.

The water may be cool or above body temperature. These treatments may be used to remove crusts and scales, to clean wounds and fistulae, to rehydrate skin, to reduce pain and pruritus, and to provide prophylaxis for patients prone to decubital problems, urine scalds, and other ills. Therapeutic treatment once or twice daily (each treatment lasting 10-15 min) is adequate. The patients should be toweled and placed in an air stream drier to dry. Other topical medications can be applied later, if needed.

In hydrotherapy, moisture is the specific agent; various additives change the actions of moisture only slightly but add their own effects. Astringents, antipruritics, moisturizers, parasiticides, and antibiotics are common additives. In general, water treatment removes crusts, bacteria, and other debris and greatly reduces the possibility of secondary infection. It promotes epithelialization and allays the symptoms of pain and burning. Cool water is antipruritic. It also softens keratin. The suppleness and softness of the skin are due to its water content, not to the oils on the surface. Dryness of the skin is recognized when any one of the following is present: roughness of the surface, scaliness, inflexibility of the horny layer, and fissuring with possible inflammation.

Cold applications cause capillary constriction and decreased blood flow.⁵³ They are often used to retard swelling, prevent hematoma formation, and allay pain and itch. Warm applications cause vasodilation, increased blood flow, increased tissue oxygenation, and increased lymph flow.⁵³

Normal skin is not a waterproof covering but is constantly losing water to the environment by transpiration. The extent of this loss depends on body temperature, environmental temperature, and relative humidity. The stratum corneum, composed of corneocytes and an intercellular matrix lipid bilayer, is the major deterrent to water loss. The lipids of this layer are derived from phospholipids and lipids secreted by the keratinocytes as they migrate to the stratum corneum and from sebum. Dry skin may result from excessive transpiration of water.

Sebum on the skin or externally applied lipid films tend to make the surface feel smoother. The flexibility of keratin is directly related to its moisture content. Major factors determining moisture content are the amount of water that the horny layer receives from the epidermis and the transepidermal loss. The transepidermal loss from the stratum corneum partially depends on the environment, especially the relative humidity. Water content of the horny layer can be increased by applying occlusive dressings or agents to prevent loss, by adding water with baths or wet dressings, or by using hygroscopic medications to attract water.

Topical Formulations

Active medications may be applied to the skin by a variety of delivery systems. These different delivery systems include, but are not limited to, the following formulations: shampoos; rinses; powders; lotions; sprays; creams, emulsions, and ointments; and gels. Each type of formulation has advantages and disadvantages that the clinician should consider when selecting a topical medication. Besides incorporating active ingredients, each type of formulation contains ingredients that act as the vehicle for delivering the active agents. These vehicles may also have certain therapeutic, irritant, or cosmetic effects, making the overall formulation more or less desirable.

In general, vehicles contain ingredients to adjust the pH, stabilize the active agents, prolong the effects of the active ingredients, promote the delivery of the active agents to the skin surface or into or through the stratum corneum, and make the product cosmetically pleasing (e.g., fragrance). The selection of the topical formulation depends on a variety of factors, most notably the surface area to be treated, the need for residual activity, the presence of hair in the area to be treated, and the nature of the lesion (e.g., moist or dry).

The active ingredients are often available in a variety of different formulations and delivery systems. In general, they have the same basic activity regardless of the formulation, but their ease of use, cost, and efficacy for the desired purpose are affected by the formulation and the method of application. The following categories of active agents are used: astringents, or drying agents; emollients and moisturizers; antiseborrheics; antipruritics; antibacterials; antifungals; antiparasitics; antiinflammatory agents; and ultraviolet screens. The following discussion describes first the different delivery systems and then the types of active ingredients.

Shampoos

Medicated shampoos contain additional ingredients that enhance the action of the shampoo or add other actions to that of the shampoo. With most shampoo formulations, the active drugs have a limited contact time because they are removed during the rinsing of the shampoo base. Some medicaments may have enough opportunity for effect or for limited absorption during a prolonged shampoo, and their addition may be justified (e.g., insecticides, salicylic acid, sulfur, tar, and antiseptics). Medicated shampoos are valuable in that they may be used for diseases involving large areas of the body or localized lesions.

Shampoo formulations have been developed that use sustained-release microvesicle technology. In one type, the microvesicles have an outer lipid membrane and contain water (Novasomes, Vétoquinol).^8,⁴⁴ The lipid membrane binds to hair and skin and has a long-term moisturizing effect as the microvesicles break down (Fig. 3-1A and B). This counteracts the drying that may occur with some medications and is therapeutic for dry skin. However, the active medication is not incorporated and will still be rinsed away.

Figure 3-1 (A) Novasome attached to canine hair shaft. (B) Scanning electron micrograph of a novasome showing the multiple layers and large cargo hold. (C) Scanning electron micrograph of a spherulite showing the multiple layers. (D) Scanning electron micrographs showing spherulites attached to hair shafts.

(Figures courtesy Vétoquinol and Virbac.)

The second microvesicle technology (Spherulites, Virbac)^8,⁴⁴ actually incorporates different ingredients, such as salicylic acid and sulfur, chlorhexidine, ethyl lactate, benzalkonium chloride, oatmeal extract, glycerin, and urea, into multiple layers of these microvesicles. Also, these microvesicles have multiple (10-1000) layers that slowly break down (Fig. 3-1C). With the breakdown of each layer, the active ingredients and the surfactants that make up these layers are released onto the hair and skin. The microvesicles can be made with different charges on the exterior; making them positively charged causes them to bind with the negatively charged hair and skin (Fig. 3-1D). Chitosanide has been used to make the microvesicles called spherulites. Besides supplying the outer cationic surface, chitosanide is an active moisturizing agent and is hygroscopic.

Efficacy of these shampoos is determined by proper use and by active ingredients. It is imperative that products be applied properly, allowed to remain on for sufficient contact time, and then properly rinsed. Education of the client regarding the use of these products is an important element and time well spent. The client should be instructed to use a clock to determine the correct contact time because subjective assessments are often inadequate. Contact time starts after the shampoo is applied, not when the bath begins. More severely affected regions should be the first areas shampooed. Sometimes, problem areas benefit from a second lathering before the final rinse.

Pharmaceutical companies provide a multitude of medicated shampoos, which often have specific indications and contraindications. It is important to become familiar with a few (perhaps one of each type) and to thoroughly understand the ingredients and their concentration and actions. Choosing the mildest or most client-pleasing shampoo that produces the desired actions often increases compliance. Strong shampoos can be harmful and helpful.

The clinician must evaluate the whole horse when selecting active ingredients, and some horses may benefit from the simultaneous use of different products. Although one shampoo may be recommended for the whole body, another shampoo may be applied to a more localized region.

Certain principles should be kept in mind when using medicated shampoos:

1. Clipping the hair coat. Clipping the hair coat and keeping the hair coat short may be critical to the proper use and maximal benefit of the product.

2. Premedicated shampoo bathing. It is often a good idea to remove grease, debris, and dirt with a nonmedicated shampoo, such as baby shampoo, or a dishwashing detergent. In this way, the medicated shampoo is better able to contact the skin, less product is used, and less expense is incurred.

3. Contact time. The shampoo should be allowed to remain in contact with the skin for 10-15 min. This allows the active ingredients to be effective and allows for the hydration of the stratum corneum. This time should be counted from the time lathering is finished and, for some owners, may be best measured with an actual timer.

4. It is important to explain, and perhaps demonstrate, the entire process of shampooing. This includes application and removal of the product.

Medicated shampoos are often classified because of their primary activity or function.

1. Emollients and moisturizers are often present in hypoallergenic shampoos and many better-quality cleansing shampoos for normal skin and hair coat. They are used when horses will be bathed frequently (weekly or more often) or for horses with slightly dry or scaly hair coats. Ingredients that moisturize are fatty acids and lipids, urea, glycerin, colloidal oatmeal, and chitosanide.

2. Antiparasitic shampoos are commonly used, but they are generally not as efficacious as antiparasitic rinses (see Chapter 6). Their main use is for quick removal of ectoparasites in foals and debilitated animals. Antiparasitic shampoos are often ineffective for adequate long-term ectoparasite control. The most common ingredients are pyrethrins and synthetic pyrethroids.

3. Antiseborrheic shampoos usually contain salicylic acid, sulfur, tar, and selenium sulfide in various combinations and strengths. These shampoos are indicated in keratinization defects (for details, see Chapter 11). They are also indicated in any other disorder associated with excessive scaling of the skin.

4. Antibacterial shampoos contain disinfectants or antibiotics such as chlorhexidine, benzoyl peroxide, iodine, ethyl lactate, benzalkonium chloride, triclosan, and sulfur. Other ingredients with less effect include quaternary ammonium compounds and phenols, alcohols, and parabens. These products are indicated whenever there is superficial bacterial infection (see Chapter 4 for discussions of their specific use). An indication for long-term use is in the allergic horse that is still prone to recurrent folliculitis even though the pruritus is controlled with the allergy therapy. In these situations, nonirritating, nondrying shampoos with antibacterial agents are often beneficial if used regularly.

5. Antimycotic shampoos contain disinfectants or antifungal agents such as chlorhexidine, sulfur, selenium sulfide, miconazole, and ketoconazole (see Chapter 5). They are used mainly as adjunctive therapy for dermatophytosis (to achieve a quick decrease of contagion) and Malassezia dermatitis. These shampoos are not effective as single agent therapy for dermatophytosis. They have been recommended as sole therapy for Malassezia dermatitis. Antimycotic shampoos may be used alone, as adjunctive therapy, or as a preventive to decrease the recurrence rate.

6. Antipruritic or antiinflammatory agents, such as 1% hydrocortisone, 0.01% fluocinolone, 2% diphenhydramine, 1% pramoxine, colloidal oatmeal, and moisturizers, are found in a variety of shampoo formulations (see Chapter 8). In general, they are adjunctive treatments and are not effective as the sole therapy unless they are used every 1-3 days. This high frequency of use is usually not acceptable to owners. Controlled studies of the use, efficacy, and absorption of glucocorticoid shampoos in horses are lacking.