Shampoo therapy

As you probably know for your everyday experience, ICF since 30 years believes in the importance of topic products, offering a large variety of shampoo and solution formulations to be used in cases of specific needs of dogs and cats with altered skin barrier.

Shampoo therapy today is known as a valid alternative to antibiotic therapy, thanks also to many articles like the one published on Veterinary Dermatology Journal (Effectiveness of a combined (4% chlorhexidine digluconate shampoo and solution) protocol in MRS and non-MRS canine superficial pyoderma: a randomized, blinded, antibiotic-controlled study, Borio S., Colombo S., La Rosa G., De Lucia M., Damborg P., Guardabassi L., Vet Dermatol 2015; 26: 339-e72). In this article it is agreed that topic treatment with shampoo and solution with chlorhexidine 4% (Clorexyderm Shampoo 4% e Clorexyderm Soluzione 4% ICF) has an effect equal to systemic treatment with Amoxicillina+ Acido Clavulanico in superficial pyoderma.

For this reason we asked two Colleagues, Chiara Noli, gratuated ECVD (European College of Veterinary Dermatology), actual president of Scientific Committee of ESVD (European Society of Veterinary Dermatology), author of many scientific texts and articles published on national and internation reviews and Irina Matricoti, Resident ECVD, to write a specific text on this theme, that, we are sure, will catch your attention.

 

SHAMPOO THERAPY

Irina Matricoti, DVM, ResECVD and Chiara Noli, DVM, DipECVD

Introduction

Therapies based on the use of shampoos have assumed extreme importance in the last decades in veterinary medicine. They are used not just for cosmetic purposes but also as therapeutic tools in many dermatologic conditions, such as bacterial or fungal infections, allergic diseases, keratinization defects or other scaling disorders. Several formulations are available on the market and the selection of the treatment will depend on the pathologic condition, the desired effect and the aim of therapy.

As a general rule, shampoos should be kept in contact with the skin for at least 10 minutes before rinsing off. The contact time allows the active agent to perform its action and water to rehydrate the stratum corneum. The majority of the shampoos usually inform on their label about the minimum contact time needed for that specific product.

The treatment frequency depends on the type of shampoo used and on the disease the clinician is dealing with. In case of skin infections the best compromise between owner’s compliance and shampoo efficacy is about twice a week. A more frequent application or the association of daily rinses is advised when topical therapy is used as the sole treatment of superficial pyoderma. In case of kerato-seborrheic disorders, the frequency of administration is variable and should be modified depending on the results and on the severity of the disease.

Shampoos formulations are composed of surfactants (cleansing, foaming or conditioning agents) and other agents, such as softeners, preservatives and degreasing agents. Surfactants are molecules with a lipophilic tail and an hydrophilic head.  In water they are able to form micellar structures that trap lipidic dirt and debris facilitating their elimination. Veterinary shampoos are formulated with different combinations of surfactants in order to combine good cleaning property and local tolerance. In fact canine and feline skin are more sensitive than human skin to topical treatments because of a thinner stratum corneum, a more alkaline skin pH and a higher follicle density, that may facilitate the penetration of active agents into the skin.

Depending on their function, shampoos are classified as: antibacterial, anti-mycotic, antipruritic/anti-inflammatory, emolient/moisturizing, antiparassitic and anti-seborrheic. However some agents have multiple effects. For example, benzoyl peroxide is both antibacterial and anti-seborrheic, chlorhexidine is active against bacteria and also yeasts; emollients and moisturizing shampoos are slightly antipruritic and find their main application in allergic diseases. Only the agents most frequently used in veterinary dermatology will be reviewed here in detail.

Antibacterial Shampoos

Antibacterial shampoos find their main application in case of cutaneous pyoderma. They may be used as adjuvant or even as a sole therapy for superficial folliculitis, acute moist dermatitis, skin fold pyoderma or impetigo. In case of deep pyoderma they should always be used concurrently with the antibiotic treatment selected on the basis of a sensitivity test. In the last decades, researchers have paid great attention to the antibacterial role of some agents because of the dramatic increase of methicillin-resistant/multidrug resistant staphylococcal bacterial infections. Luckily, today, antibacterial shampoos offer an effective alternative therapeutic approach in cases of surface and superficial pyoderma, especially in case systemic antibiotics are ineffective or potentially toxic. Antibacterial shampoos contain antiseptic such as benzoyl peroxide, phytosphingosine, ethyl lactate, glycoprotein, antimicrobial peptides and chlorhexidine. The latter is the most frequently used agent in clinical practice, both for its efficacy and for the general lack of adverse events associated to its use.

Chlorhexidine has bactericidal activity against Gram-positive and Gram-negative bacteria. Chlorhexidine disrupts the bacterial cell wall inducing leakage of bacteria. Concentrations between 2 and 4% are commonly used in veterinary dermatology. From in vitro studies it seems that higher concentrations (3-4%) have faster bactericidal activity than higher dilutions (Lloyd1999). However, in clinical trials, both formulations have been reported to be effective against Staphilococcus pseudointermedius the main causative agent of pyoderma in dogs (Murayama 2010, Loeffler 2011). In practice chlorhexidine based shampoos are commonly used in any case of pyoderma. Additionally, 4% chlorhexidine shampoo has been proven to be effective as a sole therapy in case of methicillin resistant staphylococcal superficial pyoderma (MRSP) when used twice a week associated to a daily application of 4% chlorhexidine solution (Borio 2015). This highlights the importance of topical therapy in order to decrease the use of systemic antibiotics, offers an alternative therapy in case of MRSP and supports the current recommendation of using antiseptic as a sole therapy in case of superficial skin infection.

Antimicrobial peptides (AMPs) are a wide group of proteins secreted in the skin of vertebrates, with a protective action against microorganisms. Their role is to recognize and attack viruses, bacteria and fungi. In case of bacteria, they adhere to the surface and form pores in the bacterial wall, leading to the lysis of the microorganism. They have also an important role in  immunity, as they promote recruitment and accumulation of various immune cells in the skin. Besides their bactericidal activity, AMPs inhibit the emergence of resistance. In fact bacteria, in order to become resistant to AMPs, should change thier basic structures and these mutations would lead to their death. Recently, a new shampoo containing antimicrobial peptides was released on the market. The product showed fast and complete antimicrobial activity against a panel of bacterial and fungal strains involved in canine cutaneous infections. It is, indeed a very promising product in clinical practice able to contribute to the decrease of systemic antibiotics (Ghibaudo 2016).

Benzoyl peroxide is an antibacterial agent that has also antiseborrheic properties due to its  keratolytic and  keratoplastic effect. It is metabolized in the skin to benzoic acid and oxygen. Benzoic acid inhibits epidermal proliferation and sebum production, accounting for its keratolytic effect, while oxygen radicals cause oxidation of bacteria  (Lloyd 1984; Young 2012). It is commonly used at 2.5% concentration, however it may be irritating, especially if higher concentrations are used. It should be avoided in cats. Benzoylperoxyde is also strongly degreasing through the inhibition of sebaceous gland activity, especially at concentrations above 5%. Excessive drying of the skin can occur and a hydrating conditioner may be required after each bath. Dark coated dogs tend to bleach after washing, in particular black dogs may acquire a red/brown colour.  For these reasons its main application is in seborrheic disorders, particularly in cases that are greasy or have follicular plugs, follicular casts, or comedones.

Ethyl lactate is metabolized to ethanol and lactic acid by bacterial lipases in hair follicles and sebaceous glands. Ethanol solubilizes lipids and lactic acid lowers the skin pH, resulting in a bactericidal effect. However it seems to be effective only at high concentration (above 10%) (Young 2012) and there is still controversy on its recommendation in clinical practice (Muller 2012).

Anti-seborrhoic shampoos

Anti-seborrhoic shampoos are used to manage different seborrhoic disorders and keratinization defects. They usually contain multiple agents that with keratoplastic and/or keratolytic effect. Keratolytic agents remove excessive scales by decreasing the cohesion between corneocytes and by softening the stratum corneum.  Keratoplastic agents act on the basal epidermal cells, “normalizing” the epidermal turnover and the keratinization  process. The most commonly used agents are sulfur, salicylic acid, benzoyl peroxide, selenium sulfide and propylene glycol.

Salicylic acid and sulfur based shampoos are effectively used in many  seborrheic disorders such as seborrhea sicca, sebaceous adenitis, ichthyosis, ear margin dermatosis  and superficial pyoderma with dry exfoliation. Salicylic acid  and sulfur are both  keratoplastic and keratolytic as well as mildly antipruritic and bacteriostatic. The keratolytic action of the former is due to the lowering of cutaneous pH, that results in keratin hydration and swelling of the cells of the stratum corneum.  In the case of sulfur, the keratoplastic action is mediated by a cytostatic mechanism, while the keratolytic and antiseptic actions are due to formation of hydrogen sulfide and pentatonic acid. Salicylic acid and sulphur are usually present in equal proportion, generally 2%. (Muller 2012,; Ghibaudo). Sulfur/salicylic acid shampoos are the only antiseborrheic products which can be tolerated by cats, and may be effectively used in feline patients with greasy seborrhea, feline acne or stud tail.

Selenium sulfide is a keratoplastic, keratolytic and degreasing agent. The keratoplastic action is mediated by reducing the turnover of epidermal cells while its keratolytic action is mediated by disturbing the formation of hydrogen bonds within keratin filaments. Good results have been reported in primary idiopathic seborrhea in Cocker Spaniels. Veterinary selenium sulfide shampoos are not registered in all countries. A formulation of 1% selenium sulfide combined with 2% chlorhexidine and 2% miconazole is registered in some countries and is indicated for the treatment of seborrhea oleosa complicated by Malassezia or bacterial infection. In the treatment of seborrhea sicca or after treatment of seborrhea oleosa with degreasing agents, the use of conditioners containing emollients or hygroscopic agents is indicated.

Propylene glycol is an hygroscopic (humectant) agent with high molecular weight that becomes incorporated in the stratum corneum and attracts water. It has antiseptic, lipid solvent and keratolytic properties and assists other drugs penetrate into the skin. It is used for its hygroscopic effect at 20% concentration.  Higher concentrations (up to 75%) are used when strong keratolytic properties are required, for example in case of sebaceous adenitis.

Antifungal

These products are recommended as a sole therapy in localized or mild case of Malassezia dermatitis. In case of dermatophytosis their use must be considered always as an adjuvant of systemic therapy. (Moriello 2004)

Miconazole fixes on cytochrome P450 of fungal elements and  inhibits the synthesis of ergosterol, triglycerides, phospholipids, chitin and oxidative and peroxidative enzymes. All of these modifications perturb numerous functions of the yeast membrane, leading to accumulation of hydrogen peroxides, which kill the fungal cell. Miconazole is available at 2% concentration combined with 2% chlorhexidine and it is recommended in case of Malassezia dermatitis, twice weekly for at least 3 weeks (Bond  1995; Mason 1995).

Equally chlorhexidine alone at 3% or even at lower concentrations seems to be highly effective against Malassezia (Jasmin 2003; Pasquetti 2010). Other azole-based solutions are usually recommended as adjuvant to systemic therapy in case of dermathophytosis and should not be used as sole therapy in these cases. Lime sulphur, enilconazole, and miconazole have antifungal activity in the treatment of dermatophytosis. and are generally used  twice weekly until culture negativization  is obtained (Moriello 2004).

Antipruritic and emollient shampoo

Preferred products in allergic and pruritic patients are shampoos containing humectant/emollient substances such as colloidal oatmeal, glycerin, fatty acids, sodium lactate, willowherb (Epilobium), coconut or other vegetable oils. These products are intended to moisturize the skin surface, increase the cutaneous water content by reducing the trans-epidermal water loss (TEWL), restore the lipid barrier and remove allergens form the skin (Löflath 2007).

Colloidal oatmeal is used in several shampoos due to its anti-inflammatory and antipruritic effects. It enhances the skin barrier function through its antioxidant action.

Willowherb (Epilobium) has anti-irritant, anti-inflammatory and antioxidant activity. One of the bioactive compounds present in Epilobium is oenothein B, a polyphenol which can directly modulate cellular responses. Various members of the genus Epilobium have been used in human medicine to treat a variety of diseases, such as eczema or rosacea. In veterinary dermatology it is a component of a shampoo that, in a clinical trial, has been shown to be effective in decreasing erythema and pruritus in allergic dogs (Ghibaudo).

Antiparasitic

Antiparasitic shampoos are rarely used as, unlike the topical and systemic parasiticidal agents, they do not have residual activity, and are thus inadequate for long-term flea and tick control.

In conclusion

In conclusion shampoo therapy has multiple applications in veterinary dermatology, especially in decreasing the use of  systemic antibiotic, antifungal or even antipruritic drugs. The use of antibacterial shampoos should be considered as the first line approach to superficial pyoderma, in order to rationalize the use of antibiotics and avoid the emergence of multi-resistant bacteria. Antiseborrheic shampoos represent the most appropriate therapy in keratinization defects or scaling dermatoses. Lastly shampoos should always be considered as a part of a multimodal approach in allergic patient, in order to alleviate pruritus and restore the defective skin barrier. Treatment protocol should be designed individually for each patient, depending on the active agents, animal response and owner compliance.

 

References

Bond R, Rose JF, Ellis JW et al. Comparison of two shampoos for treatment of Malassezia pachydermatis-associated seborrhoeic dermatitis in basset hounds. J Small Anim Pract 1995; 36: 99–104. 

Borio S, Colombo S, La Rosa G et al. (. Effectiveness of a combined (4% chlorhexidine digluconate shampoo and solution) protocol in MRS and non‐MRS canine superficial pyoderma: a randomized, blinded, antibiotic‐controlled study. Vet Dermatol 2015; 26: 339-e72.

Ghibaudo G, Santospirito D, Sala A et al.In vitro activity of a commercial otological solution containing a novel antimicrobial peptide on 30 clinical isolates of Pseudomonas aeruginosa from canine otitis. Abstract P69 in the Abstracts from the 8th World Congress of Veterinary Dermatology, Bruxelles 2016.

Ghibaudo G. Efficacia e tollerabilità di Ermidrà® shampoo nei confronti delle dermatiti pruriginose ed eritematose nel cane. ICF Bulletin

Ghibaudo G. Efficacy and tolerability of Zincoseb® shampoo against canine keratoseborrhoeic disorders (clinical study of 20 cases). Proceedings of the 25th Annual Congress of the European College and the European Society of Veterinary Dermatology, Bruxelles, 2012

Jasmin P, Schroeder H, Briggs M, Last R, Sanquer A. Assessment of the efficacy of a 3% chlorhexidine shampoo in the control of elevated cutaneous Malassezia populations and associated clinical signs (Malassezia dermatitis) in dogs. Proceedings of the 19th Annual Congress of the ESVD ECVD, Tenerife, 2003: 170

Lloyd DH, Lamport AI. Activity of chlorhexidine shampoo in vitro against Staphylococcus intermedius, Pseudomonas aerginosa and Malassezia pachydermatis. Vet Rec 1999; 144: 536–7

Lloyd H, Reyss-Brion A. Le Peroxyde de benzoyle: efficacite cli- nique et bacteriologique dans le traitement des pyodermites chroniques. Prat Med Chir Anim Comp 1984; 19: 445–449

Loeffler A, Cobb MA, Bond R. Comparison of a chlorhexidine and a benzoyl peroxide shampoo as sole treatment in canine superficial pyoderma. Vet Rec 2011; 169: 249.

Löflath, A, Voigts‐Rhetz V, Jaeger K. et al. The efficacy of a commercial shampoo and whirlpooling in the treatment of canine pruritus–a double‐blinded, randomized, placebo‐controlled study. Vet Dermatol 2007; 18: 427-431.

Mason KV, Atwell RB. Clinical efficacy trials on a chlorhexidine/ miconazole shampoo for the treatment of seborrhoeic dermatitis associated with an overgrowth of Malassezia pachydermatitis and coccoid bacteria. Proceedings of the 12th Annual Congress of the European College and the European Society of Veterinary Dermatology, Barcelona, 1995: 222.

Moriello K A. Treatment of dermatophytosis in dogs and cats: review of published studies. Vet Dermatol 2004 15: 99-107.

Mueller RS, Bergvall K, Bensignor E et al.. A review of topical therapy for skin infections with bacteria and yeast. Vet Dermatol 2012; 23: 330.

Murayama N, Nagata M, Terada Y et al. . Efficacy of a surgical scrub including 2% chlorhexidine acetate for canine superficial pyoderma. Veterinary dermatology 2010; 21: 586-592.

Pasquetti M, Gallo MG, Ghibaudo G et al. Use in-vitro activity of two products containing chlorhexidine against malassezia pachydermatis. Atti 10° Congresso Nazionale FIMUA Milano 2010.

Young R, Buckley L, McEwan N et al. Comparative in vitro efficacy of antimicrobial shampoos: a pilot study. Vet Dermatol 2012; 23: 36-e8.

 

 

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