Topical therapy (locally acting) is extremely important in the management of many dermatological conditions. Shampoos are nowadays widely used in veterinary dermatology.
Veterinary shampoos: definitions
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 additives1. Surfactants are amphophilic 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 absorption on various interfaces (oil/water, air/water...), modifying the properties of the interface (decrease of the interface tension and stabilisation of the interface).
In water, surfactants form micelle structures. These structures correspond to a spontaneous molecular arrangement of the amphiphilic molecules. The micelle formation process explains many of the surfactant properties and particularly their ability to emulsify, render soluble and disperse oils, dirty and debris.
Surfactants can be classified into 4 groups, according to their ionic nature: anionic, cationic, non-ionic amphoteric surfactants.
Pet shampoos have to ensure excellent cleansing of the hair and skin, leaving them soft, supple, lustrous and easy to manage. A specifically formulated combinations of surfactants is necessary in order to combine superior cleansing properties and a perfect local tolerance on canine and feline skin. Similarly, except for some very specific shampoos, pet shampoos have a physiological pH adapted to the canine and feline skin.
Another important feature of pet shampoos is ease of rinsing, because surfactants can induce skin irritation when they are not totally removed by rinsing and also, because dogs and cats (contrary to humans) often lick their fur ingesting shampoo residues.
The local tolerance of the formula is assessed by using experimental models with alternative in vitro methods if the formula ingredients are irritant, and, then using standardized in vivo tests which maximize the potential side effects of the formula. Finally, the local tolerance and efficacy are assessed on dogs and cats suffering from conditions for which the shampoo is indicated. Canine and feline 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.
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) of the bath 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), as in humans for the hairy skin, or more commonly all over the body surface of a dog or a cat for treating generalized conditions.
At the second application, the shampoo must be left on for 5 to 15 minutes, to allow the active ingredients to be properly absorbed and reach adequate levels in the deep cellular layers. The skin should then be rinsed thoroughly, for at least 5 minutes, to prevent irritation and to enable the skin to become adequately hydrated.
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 shampoo2. Their use has increased greatly in North America over the past 25 years, but they have been slower to gain acceptance in Europe3.
The efficacy of shampoos on skin hydration, the surface lipid film and stratum corneum, which are of great importance in keratoseborrhoeic disorders, can be evaluated objectively using a variety of techniques. These include transepidermal water loss (TEWL) measurement, corneocyte counts, measurement of corneal layer thickness, stripping, chemical analysis of lipid film, water content measurement, surface biopsy and corneometry4. These procedures have been deemed to be not reproducible and thus useless in evaluating effects of topical treatments in the dog. Electron microscopy could perhaps be useful.
In recent years, there has been considerable progress in improving topical formulations, especially in prolonging the action of active ingredients applied to the skin: liposomes prolong the moisturizing effect and Spherulites® increase bioavailability of therapeutic agents and promotes immediate and residual moisturising properties (reinforced by chitosanide). Also, microemulsions enhance bioavailability of active ingredients, which readily diffuse, and they also have an effective cleansing effect.
Shampoo therapy in keratoseborrhoeic disorders5
1. Keratomodulating agents work in two different ways1,5,7
Restoration of normal keratinocyte multiplication and keratinisation. A cytostatic effect is probably exerted 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 render the stratum corneum softer and reduction of intercellular cohesion increases their shedding). Agents that work in this way are called keratolytic.
Salicylic acid is a keratolytic agent. It causes a reduction in skin pH which leads to an increase in the amount of water that keratin of the stratum corneum is able to absorb and in desquamation, via direct effect on intercellular cement and intercellular junction system (desmosomes). These actions help soften the corneal layer. Salicylic acid acts synergistically with sulphur, and is often present in small quantities in shampoos. Its efficacy varies with concentration.
Coal tar is a keratoplastic (cytostatic) agent. It reduces nuclear synthesis in the epidermal basal layers7. It is also antiseptic and antipruritic. There are many different sources and varieties of this active agent. Side-effects (e.g., skin drying, discolouration of pale coats and irritation) have been reported with high concentrations (over 3%)1. Its use is contraindicated in the cat.
Sulphur is mildly keratolytic. It forms hydrogen sulphide in the corneal layer and has numerous other, mainly antiseborrhoeic, properties (see below). It is also keratoplastic, due to a direct cytostatic effect and possibly because it interacts with epidermal cysteine to form cystine, an important component of the corneal layer3,6. It is also antiseptic but is drying. It exerts synergistic activity with salicylic acid. This synergism appears optimal when both substances are incorporated into the shampoo in equal concentrations. It is gradually being replaced in topical products by other more effective keratomodulating agents with fewer side-effects, e.g., a rebound increase in seborrhoea: on cessation of effective therapy the condition may not only relapse but actually worsen.
Selenium disulphide is keratolytic and keratoplastic by reducing epidermal turnover and impairing disulphide bridge formation in keratin. It is also antiseborrhoeic (see below) but has detergent, irritant and drying effects.3,6,7 It too can cause rebound increase in seborrhoea and sometimes skin irritation. It is contraindicated in the cat.
Ammonium lactate has keratoplastic and keratolytic activity. In the management of human seborrhoea, it has been show to be effective in reducing excessive scale by virtue of its keratoplastic activity. Its mechanisms of action in seborrhoeic disorders have not yet been completely elucidated but it seems to stimulate the living epidermis, correcting defects in keratinocyte multiplication and maturation. It has important moisturising properties and is very well tolerated, even when used over prolonged periods.
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, by hydrolysing sebum and reducing sebaceous gland activity. Benzoyl peroxide exerts a follicular flushing action which is very useful when treating comedone disorders and/or follicular hyperkeratosis3,4,7,8. Side effects (irritations, erythematous rash) have been reported especially in concentrations above 5% (4). The skin may also become dry and emollients are therefore always indicated after using this product.
Zinc gluconate has antiseborrhoeic properties. Zinc, as a type 1 5α-reductase inhibitor, down regulates sebum production, and is used in human dermatology to treat acne vulgaris, both topically and orally.
Vitamin B6 (pyridoxine) plays also a role in sebum secretion and there is a synergistic effect of unknown mechanism with zinc.
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
Longhaired dogs with severe seborrhoeic disorders may be clipped. Clipping leads to more effective application and better distribution of the active ingredient. Shampoos should initially be applied several times a week. Cases should be monitored frequently. The therapeutic agent often needs to be changed following the development of side effects, rebound effects or change 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 parasitic diseases
Antiparasitic shampoos, i.e., containing organochlorines, natural pyrethrins or synthetic pyrethroids, are not considered to be as efficacious as antiparasitic rinses and dips6 and other formulations (sprays, pump-sprays, powders, spot-ons, line-ons, systemic agents), mainly because they are rinsed and are therefore short-acting 2. However, they may be indicated in scabies, cheyletiellosis, otodectic mange, tick infestation, trombiculosis and pediculosis. Insecticidal shampoos often contain synthetic pyrethroids chosen for their rapid knock-down effect: these are best used as a convenient one-off treatment to rid an animal of a resident flea infestation with little or no residual action. Normally, therefore, shampoos have limited application in the long-term management of flea infestation (pulicosis) and flea allergy dermatitis. Benzoyl peroxide shampoos are recommended in the treatment of demodicosis because of their degreasing and follicular flushing effect3,6. Many parasitic diseases (e.g., scabies, cheyletiellosis) and flea allergy dermatitis can cause a keratoseborrhoeic disorder and the affected animals will benefit from application of keratomodulating shampoos3.
Shampoo therapy in canine pyoderma
Antibacterial shampoos reduce the cutaneous bacterial population and also remove tissue debris, allowing direct contact of the active ingredient with the organism and promoting removal of the exsudate (6). Mild cases of superficial pyoderma can be treated with shampoos alone, particularly if they are used frequently at the beginning. However in most cases systemic antibiotics will be administered to ensure a more prompt response, the shampoo playing a supporting role3. In dogs that are prone to recurrent folliculitis well-tolerated antibacterial shampoos may have a prophylactic effect if used regularly i.e., every one to two weeks3,6. In cases of deep pyoderma, clipping is preferable before using shampoos (and soaks). This will prevent the formation of a sealing crust and allow the product to contact the lesions (furuncles, ulcers)6. In such cases, shampoos should be used very frequently at the initiation of treatment.
Chlorhexidine4 is a biguanide antiseptic, very effective against most bacteria (Gram + and-), except some Pseudomonas and Serratia strains. It is bactericidal by action on the cytoplasmic membrane initiating leaking of intracellular components. Concentrations vary in shampoos from 0.5 to 4% (diacetate or digluconate). An appropriate formulation is needed since chlorhexidine may show incompatibility with common surfactants (particularly anionic) used in shampoos. It has a prophylactic effect as some remains on the skin despite rinsing. It is well tolerated.
Povidone-iodine is an iodophore which slowly releases iodine to tissues4,6. The titratable iodine is usually of the order of 0.2 to 0.4 per cent. It is bactericidal and acts in a few seconds at 0.005%2.It has also a prophylactic effect due to its persistence on the skin. It is relatively drying which can be compensated by emollients in shampoos. It can be irritant and staining4.
Benzoyl peroxide (see above) is metabolized in the skin to benzoic acid and much of its microbicidal activity probably derives from the lowered skin pH3. This disrupts microbial cell membranes3,4. It is in fact an oxidizing agent, which releases nascent oxygen into the skin and produces a series of chemical reactions resulting in permeability changes and rupture of bacterial membranes4. It has an excellent prophylactic effect and is generally used in concentrations of 2 to 3%, which are well tolerated but irritation can occur at higher concentrations (erythema, pruritus and pain)4.
Ethyl lactate is hydrolysed in the skin to ethanol and lactic acid, thus lowering the skin pH and acting similarly to benzoyl peroxide3. It is used at a concentration of 10%, which rarely causes undesirable side effects (irritation, erythema, pruritus)4. When used twice weekly it can reduce the length of the course of systemic antibiotic required in canine superficial pyoderma.
Other antibacterial agents used in shampoos are hexachlorophene (not much used because of neurotoxicity), hexetidine (only available in one product) and triclosan. 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 when used alone. Shampoos with no, or only limited antifungal properties can disseminate spores. However, keratomodulating shampoos are used before antifungal topical therapy when there is a keratoseborrhoeic disorder and they are then beneficial in removing infected scales and crusts.
Topical therapy is an alternative to systemic treatment in Malassezia dermatitis. For extensive lesions antifungal shampoos or lotions are preferable. They can be used with systemic therapy, although there is no definitive evidence that the combination is of greater value than systemic treatment alone. Topical therapy alone should not be used to confirm the diagnosis, but it can maintain the patient in remission, 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, which is common in dogs with allergic skin disease. In addition, shampoos with an antipruritic effect can improve the condition of allergic dogs, provided they are used frequently (e.g., twice a week, at least at initiation of therapy). Antipruritic shampoos contain 1% hydrocortisone, 0.01% fluocinolone, 2% diphenhydramine, 1% pramoxine or colloidal oatmeal. They are considered generally as adjunctive treatments and are rarely effective as the sole therapy3,6. A shampoo specifically designed for canine atopic dermatitis has been recently developed. It contains linoleic acid and gamma linolenic acid, mono and oligosaccharides, vitamin E, and piroctone olamine. Controlled studies on the efficacy of antipruritic shampoos are lacking6.
In every skin disorders, and in particular with dry seborrhoea, there is scope for increasing the humidity of the animal's skin, after shampooing, with a moisturiser. It has been demonstrated that 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. Undiluted, they may be sprayed on after a shampoo. They should not be rinsed off.
Lipid emollients, containing lanolin alcohols, liquid paraffin or mineral oils, were borrowed from human dermatology and are now rarely used. Used as an emulsion in tepid water, they do improve coat condition, but also have a greasing effect which is a definite disadvantage.
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.
Active agents can be combined with moisturisers: colloidal oatmeal extracts and aloe vera for antipruritic activity, salicylic acid for keratolytic activity, coal tar for keratolytic and keratoplastic activity and piroctone olamine for antimicrobial properties. A lotion has been developed to complement the shampoo specifically designed for canine atopic dermatitis. It contains, in a fluid emulsion excipient, mono and oligosaccharides (free and in Spherulites®), vitamin E and linoleic acid. This lotion can be used in between shampoos.
Therapeutic plans in veterinary dermatology often include the use of medicated shampoos and should be defined on both short and long term basis to obtain the best results, to enhance the owners' compliance and to limit potential side effects. Even with the tremendous recent progresses in companion animal dermatology, there is still a certain amount of art as well as science in devising the optimum topical therapy3.
Selected references (detailed references are available on request)
1. Legeay Y (1993) Topiques en dermatologie. Encyclopédie Vétérinaire, Paris, 0700, 7p.
2. Curtis CF (1998) Use and abuse of topical dermatological therapy in dogs and cats. Part 1-shampoo therapy. In Practice, 244-251.
3. Halliwell REW (1991) Rational use of shampoos in veterinary dermatology. J Small Anim Pract 32: 401-407.
4. Guaguère E (1996) Topical treatment of canine and feline pyoderma. Vet Dermatol 7: 145-151.
5. Carlotti DN, Bensignor E (2002) Management of keratosseborrhoeic disorders. Eur J Comp Anim Pract, 12: 123-133.
6. Scott DW, Miller WH, Griffin CE (2001) Muller and Kirk's Small Animal Dermatology, 6th edition, WB Saunders Company, Philadelphia.
7. Kwochka KW (1993) Symptomatic Topical Therapy of Scaling Disorders. In: Current Veterinary Dermatology (Griffin CE, Kwochka KW, Mac Donald JM, Edrs) Mosby Year Book, St Louis, 191-202.
8. Ihrke PJ (1980) Topical therapy: specific topical pharmacologic agents-Dermatologic therapy (part II) Comp Cont Educ Prat Vet 11: 156-164.