Topical (locally acting) therapy is important in the management of many dermatological conditions because the skin is readily accessible to medications. Several formulations are available for the prescribing veterinary surgeon and may include many active ingredients. The active ingredients penetrate the skin through the intercellular spaces (lipophilic molecules), through the epidermal cells (ion compounds) and above all through the hair follicles in animals, particularly for ionized molecules. Canine skin is often more sensitive than is human skin due to anatomical and physiological differences, including differences in the thickness of the stratum corneum, skin pH and hair follicle density which can facilitate cutaneous penetration of active ingredients. The use of shampoos will be emphasized in this paper; antiparasitic and auricular topical products are beyond its scope.
Ointments, Creams and Gels
Creams and ointments are a mixture (emulsion) of oil and water. They are usually used on dry skin, and not on oozing (exudative) areas. Creams (made of oil dispersed in water) are more aqueous than ointments (made of water dispersed in oil). Gels are composed of a thixotropic (gel at rest, but fluid when agitated) base (usually containing propylene glycol), pass through the haircoat to the skin and are less messy and occlusive than creams and ointments. These bases are used as vehicles for many agents:
Topical glucocorticoids are useful in veterinary dermatology and perhaps have been neglected. They have anti-inflammatory and antipruritic properties as well as antiproliferative and immunosuppressive effects. These formulations are useful for localised lesions (e.g., cheilitis, blepharitis, pododermatitis, nasal lesions, excoriations and pyotraumatic dermatitis). Many molecules are available in human dermatology, classified from class I (the least potent) to class IV (the most potent). Some potent human formulations can be used in the dog (e.g., clobetasol propionate); most of the veterinary formulations contain less potent agents. Tachyphylaxis, atrophy and microbial infections can occur in cases of overuse.
Immunomodulators: tacrolimus, a calcineurin inhibitor has been shown to be effective in the treatment of localized lesions of canine atopic dermatitis; imiquimod, an inhibitor of gamma-interferon synthesis, may be helpful in treating some preneoplastic and neoplastic diseases (papillomas, Bowen's disease, actinic keratosis, basal and squamous cell carcinomas).
Antibiotics: formulations containing fusidic acid and mupirocin are useful for treating localized lesions of pyoderma.
Antifungals: human products containing azole derivatives, nystatin or amphotericin B can be used on localized lesions of dermatophytosis, Malassezia dermatitis or candidiasis.
Combined formulations: some veterinary products contain a weak glucocorticoid and an antibiotic (e.g., neomycin and hydrocortisone) or more active ingredients also including an antifungal agent (e.g., neomycin, thiostrepton, triamcinolone and nystatine). These are useful in non infectious lesions, for their anti-inflammatory and preventive anti-microbial properties but should not be used to treat pyoderma or fungal diseases.
Lotions, Rinses and Sprays
Lotions are liquids in which active agents are dissolved or suspended. Rinses are concentrated and must be diluted before use. Pump-sprays containing lotions are commonly used in canine dermatology (after or in between shampoos). They contain different agents:
Antibacterials: chlorhexidine can be used in lotions, as an antibacterial agent. Piroctone olamine is used in sprays for its antimicrobial properties.
Antifungals: a lotion containing enilconazole is effective against both dermatophytosis and Malassezia dermatitis.
Glucocorticoids: small containers allow the treating of localized lesions, as creams and ointments do. Several glucocorticoids are available, usually not the most potent. Large containers (e.g., triamcinolone) can be very useful to treat generalized conditions.
Nonsteroidal antipruritic formulations, e.g., containing pramoxine, colloidal oatmeal or aloe vera can be very useful. A spray containing Hamamelis extract and menthol as become popular to treat localized lesions and has been shown to kill Malassezia. A lotion has been developed to complement a shampoo specifically designed for canine atopic dermatitis (see below). It contains, in a fluid emulsion excipient, mono and oligosaccharides (free and in Spherulites®), vitamin E and linoleic acid.
Moisturisers: skin hydration is less in dogs with scaling than in normal dogs. Moisturisers lubricate, rehydrate, soften the skin and restore an artificial superficial skin film. Diluted in water, they can be massaged into the skin or applied as a lotion/rinse. Undiluted, they may be sprayed on after a shampoo. They should not be rinsed off. Lipid emollients borrowed from human dermatology and used as an emulsion in tepid water, improve coat condition, but have a greasing effect. Non-lipid emollients have rehydrating and softening properties. They reduce odour and improve coat appearance without the greasing effect. The high molecular weight of their active ingredients and their hygroscopic nature make them effective surface-protecting therapeutic agents. Examples include lactic acid, glycerine, propylene glycol, urea and chitosanide.
Recently a micro-emulsion spray and a spot-on formulation containing phytosphingosine have been launched. Phytosphingosine is a proceramid and a natural component of the epidermis, with restructuring, antiseborrhoeic and also antimicrobial effects.
Traditional shampoo formulations are composed of surfactants (cleansing agents, foaming agents and conditioners) as well as thickeners, softeners, sequestering agents, preservatives, fragrance and sometimes opacifiers and colouring additives. Surfactants are amphiphilic molecules, i.e., molecules with a dual affinity, both for water and oil. Surfactants are composed of a hydrophilic part (hydrophilic "head") and a lipophilic part ("lipophilic tail"). They are called surfactants (surface active ingredients) due to their propensity for absorption on various interfaces (oil/water, air/water...), modifying the properties of the interface (decreasing the interface tension and stabilisation of the interface). In water, surfactants form micelle structures allowing surfactant to emulsify, render soluble and disperse oils, dirt and debris. Surfactants can be classified into 4 groups, according to their ionic nature: anionic, cationic, non-ionic, and amphoteric surfactants. Pet shampoos are formulated combinations of surfactants combining superior cleansing properties, a perfect local tolerance (assessed in vitro and in vivo), a physiological pH adapted to the canine skin and easiness of rinsing. Shampoos are ideal vehicles to treat the haired and sensitive skin of dogs.
How to use Veterinary Shampoos
Ideally, a shampoo possessing both cleansing and therapeutic properties should be applied twice at each use. The mechanical effect (elimination of scales and crusts) is beneficial in all cases. Water rehydrates the stratum corneum although this effect is temporary in the absence of moisturisers. A shampoo can be used in a limited area (e.g., chin, feet, dorsolumbar, ventral areas), or more commonly all over the body surface. At the second application, the shampoo must be left on for 5 to 15 minutes, to allow the active ingredients to be properly absorbed. The skin should then be rinsed thoroughly. The shampoo may be applied several times a week for 2 weeks. The frequency is then reduced to give the longest interval over which treatment is still effective, usually about 1 to 2 weeks.
Efficacy of Shampoos
Clinical improvement is the main criterion in evaluating the efficacy of a shampoo. The efficacy of shampoos on skin hydration, the surface lipid film and stratum corneum, which is of great importance in keratoseborrhoeic disorders, can be evaluated objectively using a variety of techniques, including transepidermal water loss (TEWL) measurement and many others, but they have been deemed to be not reproducible and thus useless. Prolonging the action of active ingredients has been made possible: liposomes prolong the moisturizing effect and Spherulites® increase bioavailability of therapeutic agents and promote immediate and residual moisturising properties (reinforced by chitosanide). Also, microemulsions enhance bio-availability of active ingredients, which readily diffuse, and they also have an effective cleansing effect.
Shampoo Therapy in Keratoseborrhoeic Disorders
1. Keratomodulating agents work in two different ways:
Restoration of normal keratinocyte multiplication and keratinisation. Some of them probably exert a cytostatic effect on basal cells, thereby reducing their rate of division. Agents working in this way are called keratoplastic (keratoregulating);
Elimination of excess corneal layers, by increasing desquamation (ballooning of corneocytes rendering the stratum corneum softer and a reduction of intercellular cohesion that increases their shedding). Agents that work in this way are called keratolytic.
Salicylic acid is a keratolytic agent. Its efficacy varies with concentration. Coal tar is a keratoplastic (cytostatic) agent. It is also antiseptic and antipruritic and has many different sources and varieties. Side-effects are possible. Sulphur is mildly keratolytic. It is also keratoplastic and antiseptic. Salicylic acid and sulphur act synergistically in particular when both substances are incorporated into the shampoo in equal concentrations. Selenium disulphide is keratolytic and keratoplastic but has detergent, irritant and drying effects. Ammonium lactate has keratoplastic and keratolytic activity. It has important moisturising properties and is very well-tolerated, even when used over prolonged periods. Phytosphingosine helps restructuring the stratum corneum.
2. Antiseborrhoeic agents inhibit or reduce sebum production by the sebaceous glands, and help clear the ducts. Sulphur (see above) is a classic antiseborrhoeic agent, and may trigger a rebound effect. Selenium disulphide (see above) is antiseborrhoeic and may also cause a rebound effect. Benzoyl peroxide, in addition to being antibacterial, is antiseborrhoeic, and exerts a follicular flushing action which is very useful when treating comedone disorders and/or follicular hyperkeratosis. Side-effects (drying effect, irritations, erythematous rash) have been reported especially in concentrations above 5%. Zinc gluconate has antiseborrhoeic properties by downregulating sebum production. Vitamin B6 (pyridoxine) also plays a role in sebum secretion and there is a synergistic effect, of unknown mechanism, with zinc. Phytosphingosine helps controlling seborrhoea.
3. Essential fatty acids and moisturisers: various veterinary shampoos have incorporated essential fatty acids for their softening and moisturising properties. Some shampoos contain moisturisers such as glycerine, lactic acid and fatty acid polyesters.
4. How to use shampoos in keratoseborrhoeic disorders: long-haired dogs with severe seborrhoeic disorders may be clipped. The therapeutic agent often needs to be changed following the development of side effects, rebound effects or changes in clinical presentation (e.g., transition from greasy seborrhoea to dry seborrhoea). The more severe the dermatitis is, the more active and potent the shampoo must be and the more frequent will be the applications. For mild and/or pityriasiform keratoseborrhoeic disorders, keratolytic agents should be selected whereas for severe and/or psoriasiform disorders, keratoregulating (keratoplastic) agents will also be used. In all cases but particularly in greasy seborrhoea, antiseborrhoeic agents may be useful.
Shampoo Therapy in Canine Pyoderma
Antibacterial shampoos reduce the cutaneous bacterial population and also remove tissue debris and exudate, allowing direct contact of the active ingredient with the organism. Mild cases of superficial pyoderma can be treated with shampoos alone. However in most cases systemic antibiotics will be administered, the shampoo playing a supporting role. In dogs that are prone to recurrent folliculitis antibacterial shampoos may have a prophylactic effect if used regularly. In cases of deep pyoderma, clipping is preferable to prevent the formation of a sealing crust and allow the product to contact the lesions (furuncles, ulcers). Chlorhexidine (0.5 to 4%, diacetate or digluconate) is very effective against most bacteria (gram + and -), excepting some Pseudomonas and Serratia strains. It has a prophylactic effect as some remains on the skin despite rinsing and is well tolerated. Povidone-iodine releases iodine to tissues (0.2 to 0.4 per cent). It has also a prophylactic effect but is relatively drying, can be irritating and staining. Benzoyl peroxide (2 to 3%) has a strong microbiocidal activity, an excellent prophylactic effect but irritation can occur at higher concentrations (erythema, pruritus and pain). Ethyl lactate is used at a concentration of 10%, which rarely causes undesirable side effects (irritation, erythema, pruritus). When used twice weekly it can reduce the length of the course of systemic antibiotics required in canine superficial pyoderma. Piroctone olamine is an antifungal agent (see below) which also has antibacterial properties.
Shampoo Therapy in Fungal Diseases
Antimycotic shampoos (ketoconazole, miconazole, 1:1 combination of miconazole and chlorhexidine) reduce the infectivity in cases of dermatophytosis but are not effective in treating it as sole therapy. Keratomodulating shampoos can be used before antifungal topical therapy. Topical therapy is an alternative to systemic treatment in Malassezia dermatitis. For extensive lesions antifungal shampoos or lotions are preferable. Topical therapy alone should not be used to confirm the diagnosis, but it can maintain the patient in remission with systemic therapy, thus confirming the diagnosis. Shampoos containing miconazole (2%), chlorhexidine (2 to 4%), a combination of both (2% each), ketoconazole (2%), a combination of chlorhexidine (2%) and ketoconazole (1%) or piroctone olamine are the most appropriate.
Shampoo Therapy in Allergic Diseases
All shampoos are likely to remove allergens from the skin, which is believed to be helpful in canine atopic dermatitis. They also help to rehydrate dry skin. Shampoos with an antipruritic effect (1% hydrocortisone, 0.01% fluocinolone, 2% diphenhydramine, colloidal oatmeal) can be good adjunctive treatments. A shampoo specifically designed for canine atopic dermatitis contains linoleic acid and gamma linolenic acid, mono and oligosaccharides, vitamin E, and piroctone olamine and has been shown to be useful.
Conclusion: Optimising Topical Therapy
Topical therapy is symptomatic and complimentary, and thus often used along with specific treatments, mainly systemic. An appropriate formulation, judiciously selected active ingredients and the appropriate frequency of application make it essential. The prescription varies according to each case and must take into account the nature and extent of the lesions, the concurrent specific treatment, the animal's temperament and willingness of the owner to devote the necessary time, and the concentration and potential side effects of the active ingredients. Choices should be made on both a short and long term basis. Communication is important and should underline the great value of medicated shampoos for the treatment of skin diseases of an animal with a haired skin.
References are available upon request.