Topical therapy in veterinary dermatology
Frane Banović and Nikša Lemo*
Frane BANOVIĆ, DVM, College of Veterinary Medicine, University of Georgia, Athens, GA, USA; Nikša LEMO*, DVM, PhD, Full Professor, (Corresponding author, e-mail: firstname.lastname@example.org), Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia
Topical therapy is extremely important in the management of allergic, infectious, and seborrheic disorders. Numerous commercial formulations are available for veterinarians and may include diverse active ingredients. 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.
Therefore, it is highly recommended to use topical formulations registered only for applications in dogs. The application of topical formulations for treatment of canine superficial pyoderma, keratoseborrhoeic disorders and atopic dermatitis will be emphasized in this report.
Key words: topical therapy; canine superficial pyoderma; keratoseborrhoeic disorders; atopic dermatitis
How do I treat canine superficial pyoderma topically?
Patients with canine atopic dermatitis exhibit frequent, sometimes recurrent, staphylococcal and yeast skin infections, which can exacerbate pruritus and dermatitis; therefore, patients predisposed to secondary staphylococcal pyoderma should be considered and screened for canine atopic dermatitis (Olivry et al., 2010; Hillier et al., 2014).
With the emergence of multi-drug resistant bacteria-including Staphylococcus species-that are important to human beings and companion animals, topical antimicrobials have gained popularity as an alternative to systemic antibiotics (Olivry et al., 2010; Mueller et al., 2012). Topical treatment is an effective primary option for focal and generalized superfi cial pyoderma; topical therapy decreases bacterial counts and reduces surface colonization of bacteria, thus helping to prevent or reduce the incidence of recurrences. Furthermore, topical therapy is safer and achieves higher antimicrobial concentrations compared with systemic antibiotics (Olivry et al., 2010).
What is an effective active antiseptic ingredient?
However, there is a lack of in vivo efficacy and comparative studies for most of these products. Thus, it is recommended that products should be selected based on evidence based medicine and randomized blinded clinical studies.
In 2012, a review of topical therapies concluded that the best evidence of efficacy in cases of canine pyoderma exists with antiseptic products containing either chlorhexidine or benzoyl peroxide (Banovic et al., 2017a). Furthermore, a recent published study comparing the efficacy of topical chlorhexidine (combined shampoo and spray formulations both at 4%) with systemic amoxicillin-clavulanic acid for the treatment of canine superficial pyoderma has shown that topical therapy with chlorhexidine digluconate products alone may be as effective as systemic therapy with amoxicillin-clavulanic acid (Mueller et al., 2012).
Chlorhexidine, a bisbiguanide antiseptic, is most commonly used in veterinary dermatology at various concentrations (0.5%-4%) of the water soluble gluconate form, however, some in vitro studies have also indicated that a higher concentration of the active ingredient is not always more effective (Olivry et al., 2010; Mueller et al., 2012; Jeffers, 2013).
Synthetic cationic polymers are becoming widely used in people as antimicrobials due to their broad-spectrum bactericidal activities and high therapeutic index. Polihexanide (polyhexamethylene biguanide, PHMB) has a broad antimicrobial spectrum, including Gram-positive and Gram-negative bacteria, biofilm-building bacteria, and fungi including Candida spp. (Hübner and Kramer, 2010).
Similarly to chlorhexidine, polihexanide interacts with acidic, negatively charged phospholipids in the bacterial membrane, leading to increased fluidity, permeability and loss of integrity, followed by the death of the organism (Ikeda et al., 1984; Gilbert and Moore, 2005). The advantage of polihexanide is that it does not contain the toxic terminal chlorobenzene substituents like chlorhexidine (Hubner et al., 2010). The results of a recent study indicate that polihexanide has comparable in vitro antimicrobial efficacy with chlorhexidine against common canine pathogenic microorganisms (S. pseudintermedius, Pseudomonas aeruginosa) affecting the skin and presents a potential alternative agent to chlorhexidine for skin and wound antisepsis in veterinary medicine (Banovic et al., 2013). Thus, further antimicrobial efficacy should be confirmed by in vivo studies on local tolerability and clinical efficacy in dogs.
What method of application will best reach the site of infection?
Spot treatments (ointments, gels, creams) work best for focal/multifocal lesions and hairless areas; wipes are ideal for intertriginous areas (facial folds, lip folds, interdigital areas, perivulvar region); and sprays are beneficial for focal lesions or sparsely haired areas (abdomen, ventral thorax, axillary area) (Mueller et al., 2012; Jeffers, 2013).
How much contact time is required and how frequent should the therapy be applied?
The duration of contact time is based on in vitro data showing stronger kill against the most common skin pathogens, like S. pseudintermedius, with longer antiseptic time exposures. Client compliance can be an issue in topical therapy; when a medicated shampoo is used, it is imperative that the owner understands the importance of contact time before rinsing. Bathing should be performed 2 to 3 times a week when used as a monotherapy (Mueller et al., 2012; Jeffers, 2013; Hillier et al., 2014; Borio et al., 2015), frequent bathing should be continued for 7 days past resolution of clinical signs associated with the infection.
Other therapies (sprays, wipes, gels, lotions) should ideally be applied twice a day until clinical resolution; these may be used immediately in case of pyoderma recurrences (Mueller et al., 2012; Jeffers, 2013; Borio et al., 2015). It has been suggested that crusts associated with pyoderma be removed before application of these products. To prevent potential removal by the patient (licking the areas), the products may be applied at times when the patient can be distracted via feeding or before walks.
In cases of canine atopic dermatitis and after the superficial pyoderma resolution, once weekly bathing should be continued using non-antiseptic moisturizing oatmeal based shampoos.
Topical antiseptics can disrupt cutaneous homeostasis by nonspecific killing of the normal microflora. Therefore, using antiseptic shampoos as continuous indefinitely treatment on a weekly to biweekly basis may result in altered balance of the microbiota, a condition known as dysbiosis. This could predispose atopic patients to more recurrent flare ups.
Are there new developments in topical products for superficial pyoderma?
However, these antimicrobial assays have been performed under non-physiological conditions, using bacterial growth media rather than a culture environment that closely resembles canine skin. Further in vivo studies are needed to evaluate if this very promising product is able to contribute to the decrease of systemic antibiotics for superficial pyoderma in clinical practice.
Diluted bleach (a.k.a. sodium hypochlorite hereafter referred to solely as “hypochlorite”) represents an inexpensive and widely available topical antiseptic. Dilute bleach baths (to an approximate concentration of 0.005% hypochlorite) have been shown to remarkably reduce the severity of infected atopic dermatitis (AD) in children over 3 months duration (Huang et al., 2011).
The author of a recent review on the therapeutic approach for canine superficial pyoderma recommended the application of 0.06–0.12% diluted sodium hypochlorite solution, two to four times weekly, as an adjunctive topical therapy for this disease (Bloom, 2014). However, the recommendation for this dilution range was based solely on personal clinical experience. Given the lack of evidence for diluted bleach usage in dogs, our initial study revealed excellent in vitro antimicrobial effectiveness of diluted sodium hypochlorite against isolates of S. pseudintermedius, P. and Malassezia (M.) pachydermatis from atopic dogs (Banovic and Lemo, 2014). Furthermore, we evaluated the antiseptic efficacy and local side effects of a single 0.05% and 0.005% diluted bleach solution application on the skin of healthy dogs (Banovic et al., 2017b). The single application at both concentrations revealed excellent tolerability as well as reduction in bacterial load evaluated using contact agar plates with neutralization medium.
We followed with a repeated diluted bleach baths (0.005%) study in healthy dogs; twice weekly bleach baths for 15 minutes were safe and there was no signs of skin irritation or dryness in any dog (Banovic, unpublished data).
Interestingly, there was no change staphylococcal diversity and skin microbiome evaluated through bacterial 16S rRNA gene sequencing (Banovic, unpublished data). Further research is needed to evaluate how bleach baths modulate skin barrier function and reduction in itch intensity in atopic dogs.
An alternative to bleach soaks may be a 0.011% hypochlorous acid containing solution (Veterycn, VF; Innovacyn, Rialto, CA, USA) marketed for topical treatment in veterinary medicine. However, a recent pilot study evaluating this product failed to demonstrate efficacy in treating canine pyoderma when used twice a day for 3-4 weeks (Udenberg et al., 2015).
Which topical antibiotics should I use for canine pyoderma?
Mupirocin, an antibiotic developed from the fermentation of Pseudomonas fluorescens (Godbeer et al., 2014), Mupirocin is a bacteriostatic antibiotic that reversibly binds to isoleucyl tRNA synthetase to disrupt protein synthesis and is widely used to eliminate nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) in human MRSA carriers (Godbeer et al., 2014).
Mupirocin has been used only on a limited basis in veterinary medicine but is approved in the United States for the treatment of bacterial skin infections and superficial pyoderma in dogs.
Silver sulfadiazine cream can be very useful in the treatment of localized pyoderma with Pseudomonas spp. Silver salts precipitate proteins and interfere with bacterial metabolic activities (Rosenkrantz , 2006). It has been shown to be effective in vitro against Pseudomonas at concentrations ranging from 0.1 to 1% (Rosenkrantz , 2006).
How do I treat Malassezia dermatitis topically?
Topical therapy for seborrheic skin diseases
- a cytostatic effect is exerted on basal cells, thereby reducing their rate of division (keratoplastic).
- elimination of excess corneal cells, by increasing desquamation. Most antiseborrheic shampoos also eliminate excess corneal layers, by increasing desquamation. This is thought to be a result of ballooning of corneocytes that makes the stratum corneum softer and reduces the intercellular cohesion of the corneocytes and results in increased desquamation. Agents that function in this way are called keratolytic (Rosenkrantz , 2006).
There are many keratoplastic and keratolytic agents that are commercially available in shampoo formulations.
Salicylic acid is a keratolytic agent that reductes skin pH which leads to an increase in the amount of water that keratin is able to absorb (Rosenkrantz, 2006). Stratum corneum hydratation increases and corenal layer softens which allows desquamation. Salicylic acid acts synergistically with sulphur, and is often present in small quantities in shampoos (Rosenkrantz , 2006). Sulphur is mildly keratolytic and has numerous other, mainly antiseborrhoeic, properties.
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 layer (Rosenkrantz , 2006).
It exerts synergistic activity with salicylic acid. This synergism appears optimal when both substances are incorporated into the shampoo in equal concentrations (Rosenkrantz , 2006). Selenium disulphide is keratolytic and keratoplastic by reducing epidermal turnover and impairing disulphide bridge formation in keratin. It is also antiseborrhoeic but also has irritant and drying effects.
Phytosphingosine is a proceramid (ceramides are components of the extra cellular sheets of lipids in the stratum corneum) and a natural component of the epidermis, with anti-inflammatory and antimicrobial effects.
Benzoyl peroxide, in addition to being antibacterial, is antiseborrhoeic, by hydrolyzing sebum and reducing sebaceous gland activity (Rosenkrantz, 2006). The skin may also become dry and moisturizers are therefore always indicated after using this product.
How to use shampoos in keratoseborrhoeic disorders?
With time, frequency of application can gradually be reduced to give the longest interval over which treatment is still effective, usually about 2 weeks.
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.
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 (Rosenkrantz , 2006). In all cases but particularly in greasy seborrhea, antiseborrhoeic agents may be useful.
Concept of “proactive therapy” with topical steroids in canine atopic dermatitis
As suggested in human AD (Wollenberg et al., 2008), clearing the skin lesions with daily application of steroids for 1-2 weeks should be followed with the intermittent use of the same product (e.g. 2-3 times/week) even if visible lesions have disappeared. This “proactive treatment” approach reduces the risk of flares and extends the time of remission.
The long-term proactive application of hydrocortisone aceponate (Cortavance, Virbac) spray administered on two consecutive days each week or twice weekly was shown to be effective and well-tolerated in atopic dogs with skin and recurrent ear infections, prolonging remission times of flares in comparison with reactive therapy (therapy only when clinical signs are visible) (Lourenco et al., 2016).
Improving epidermal barrier dysfunction in canine atopic dermatitis
Weekly bathing with a mild nonirritating shampoo and postbathing topical moisturizers are recommended for each patient; this therapy provides a direct soothing effect to the skin, physically removes surface allergens, and increases skin hydration (Olivry et al., 2010; Olivry et al., 2015).
According to the systematic review of clinical trials, essential fatty acid supplementation is indicated only for long-term management of canine atopic dermatitis as an adjunctive treatment (Olivry et al., 2010; Olivry et al., 2015) the clinical benefit of essential fatty acid supplements on the skin may take up to 2 months to be seen. In recent years, some topical (spot-on, spray, shampoo, emulsion) formulations containing fatty acids and ceramides have been introduced for dogs with canine atopic dermatitis; however, their efficacy is inconsistent, and veterinarians should weigh their benefit and cost before deciding to use them (Olivry et al., 2010; Olivry et al., 2015).
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Topikalna terapija u veterinarskoj dermatologiji
Frane BANOVIĆ, dr. med. vet., College of Veterinary Medicine, University of Georgia, Athens, GA, USA; dr. sc. Nikša LEMO, dr. med. vet., redoviti profesor, Veterinarski fakultet Sveučilišta u Zagrebu, Zagreb, Hrvatska
Topikalna ili lokalna terapija iznimno je važna u liječenju alergijskih, infektivnih i seboroičnih bolesti kože. Veterinarima su dostupne brojne komercijalne formulacije i mogu uključivati različite aktivne sastojke.
Koža pasa često je osjetljivija od ljudske kože zbog anatomskih i fizioloških posebitosti, uključujući i razlike u debljini rožnatog sloja, pH kože i gustoće dlačnih folikula koji mogu također olakšati prodiranje aktivnih sastojaka lokalne terapije. Stoga je preporučljivo koristiti formulacije registrirane „samo za primjenu u pasa.“ U ovom preglednom članku naglašava se primjena lokalne terapije za liječenje površinske upale kože, keratoseboroičnih poremećaja i atopijskog dermatitisa u pasa.
Key words: lokalna terapija, površinska upala kože, keratoseboroične bolesti, atopijski dermatitis
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