11/21/2019

The Crucial Role of Options for management of skin Topical Therapy disease in Managing skin disease in dogs

Joel Griffies, DVM Diplomate ACVD Animal Dermatology Clinic Marietta, GA

www.animaldermatology.com 1 2

Topical Therapy Topical Therapy

Disadvantages Advantages ◦ More labor intensive/time consuming ◦ Ease of access ◦ Effect may take longer ◦ Safety ◦ Cost? +/- ◦ Lack of systemic side effects ◦ Useful Adjunctive ◦ Replacement for systemic therapies in some

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Topical therapy

MYTH - Bathing is bad Questions/Objectives ◦When & Why is topical therapy a useful Reality tool ◦Bathing has been shown to significantly ◦How do we choose what to prescribe help outcome in a variety of skin disorders ◦How does that differ with the condition ◦IF – we’re using the right products being treated for the right problem…

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Topical therapy Normal epidermal anatomy Questions/Objectives

◦When & Why is topical therapy a useful Formation of stratum corneum & tool cornified cell envelope Extrusion of lamellar granules ◦Allergy (ceramides, cholesterol, ◦Infections free fatty acids) ◦Parasites Lipid production (lamellar granules) ◦Keratinization defects Keratin production Proliferative stem cells ◦Many others

Cell layers of the epidermis. From Muller & Kirk’s Small Animal Dermatology. We have access! Modified from Proksch E Folster-Holst R, Brautigam M et al : Role of the epidermal barrier in atopic dermatitis. J Dtsch Dermatol Ges 7:899-910 Fig. 2. p901

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Normal epidermal anatomy

Formation of stratum corneum & cornified cell envelope Extrusion of lamellar granules (ceramides, cholesterol, free fatty acids) Lipid production (lamellar granules) Keratin production Proliferative stem cells

Cell layers of the epidermis. From Muller & Kirk’s Small Animal Dermatology. Modified from Proksch E Folster-Holst R, Brautigam M et al : Role of the epidermal barrier in atopic dermatitis. J Dtsch Dermatol Ges 7:899-910 Fig. 2. p901

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Epidermal Anatomy Practical Application

Stratum corneum ◦ Layers of cornified epithelial cells ◦ Surrounded by a lipid envelope Composed of ◦ Ceramides (sphingosine + fatty acid) ◦ Free fatty acids ◦ Cholesterol

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The Epidermal Barrier Electron Microscopic Observations of Stratum & Corneum Intracelular Lipids in Normal and Atopic Dogs Atopic Dermatitis Inman et al. Vet Pathology 2001 Current Research Atopic dogs Role of epicutaneous allergen exposure ◦ Deposition of lipid into stratum corneum variable ◦ Many areas devoid of epidermal lipids ◦ When present lamellae exhibited abnormal and/or incomplete structure

◦ Both thickness and continuity of stratum corneum lipids were significantly decreased in atopic dogs

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Characterization and quantification of ceramides Electron Microscopic Observations of Stratum in the nonlesional skin of canine patients with atopic Corneum Intracelular Lipids in Normal and Atopic Dogs dermatitis compared with controls Inman et al. Vet Pathology 2001 (Reiter et al. Veterinary Dermatology 2009)

Ceramide deficiencies identified in the stratum corneum of Atopic dogs Normal Atopic dogs compared to normal dogs

Decreased percentages of ceramide 1 and 9 and increased cholesterol ◦ Ceramide 1 - a vital component of the lipid barrier ◦ Carrier of linoleate – an important Fatty acid in forming the barrier

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Epidermal Barrier: Topical Opportunities?

Addition of ceramides, fatty acids (esp linoleic) as replacement and repair ◦ Additives in ◦ Focal application ◦ Leave-on conditioners Regular bathing to remove ◦ Sources of potential infection ◦ Potential allergens

… more to come

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Topical Therapy: Topical Therapy The right products?

Therapeutic bathing Our recommendations as veterinarians?

◦First understand what you’re treating

◦Then know what’s available AND proven effective

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Shampoo Categories Categories

Cleansing Cleansing Soothing/Anti-pruritic ◦ HUGE variety of ingredients, technology and Antimicrobial claims. Some verified, some not Antiseborrheic ◦ Encapsulated moisturizers ◦ Key components for better health of the epidermis ◦ Ceramides ◦ Fatty acids (esp. linoleic)

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Shampoo Categories Bathing as a tool Cleansing for management of skin disease ◦ Selection advice ◦ Use a reputable company ◦ Take advantage of support and advice ◦ Find ones you like that deliver positive results and feedback from clients! ◦ There IS a difference

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Shampoo Categories - Topical Therapy Therapeutic The right products for the right problem Soothing/Anti-pruritic Clinical Approach ◦ Emollients and moisturizers ◦ Ideally ◦ Topical antihistamines & anesthetics ◦ Match product/ingredient with skin disease being treated Antimicrobial ◦ Antibacterial ◦ Shampoos as therapeutic tools ◦ Combination Antibacterial/ ◦ Prescribe based on ingredients and formulation Antiseborrheic (instead of price or marketing) ◦ Mild ◦ Moderate ◦ Aggressive

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem Soothing/Anti-pruritic Soothing/Anti-pruritic ◦ Indications ◦ Common ingredients Properties ◦ Mild to moderate pruritus ◦ Emollient Oatmeal - Moisturizing ◦ Allergy (atopy, food allergy, flea allergy) ◦ Fatty acids (linoleic) - Barrier restoration ◦ Xeroderma ◦ Ceramides, phytosphingosine ◦ Without infection ◦ Aloe ◦ Pramoxine ◦ Hydrocortisone - Topical anesthetic - Anti-inflammatory

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Soothing/Anti-pruritic Soothing/Anti-pruritic ◦ Common ingredients ◦ Common ingredients ◦ Emollient Oatmeal ◦ Emollient Oatmeal ◦ Fatty acids (linoleic) ◦ Fatty acids (linoleic) ◦ Ceramides, phytosphingosine ◦ Ceramides, phytosphingosine ◦ Aloe ◦ Aloe ◦ Pramoxine ◦ Pramoxine ◦ Hydrocortisone ◦ Hydrocortisone

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Antimicrobial Antimicrobial ◦ Antibacterial ◦ Indications ◦ Combination antifungal/antibacterial ◦ Treatment AND prevention of… ◦ Bacterial pyoderma/overgrowth superficial and deep ◦ dermatitis ◦ Dermatophytosis?

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Impression smear cytology Impression smear cytology

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Topical Therapy Comparative in vitro efficacy of antimicrobial shampoos: a pilot study The right products for the right problem Young, et al. ; VETERINARY DERMATOLOGY Feb 2012 Antimicrobial Compared effects of several shampoos against MSSP, MRSP, Pseudomonas and Malassezia ◦ Antibacterial Chlorhexidine gluconate 2% Ethyl lactate, 10% ◦ Chlorhexidine Do they all work the nitrate 2% chitosanide ◦ Benzoyl peroxide same? nonionic Spherulites ◦ Acetic acid/Boric Acid Chlorhexidine gluconate 3% ◦ Ethyl lactate Are they monosaccharides Chloroxylenol 2% 2% ◦ Chloroxylenol interchangeable? chitosanide nonionic Spherulites sodium thiosulphate 2%;

Chlorhexidine gluconate 4%... Acetic acid, 2% boric acid, 2% Benzoyl peroxide, 2.5% propylene glycol…

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Comparative in vitro efficacy of antimicrobial Activity of chlorhexidine shampoo in vitro against shampoos: a pilot study staphylococcus intermedius, Pseudomonas Young, et al. ; VETERINARY DERMATOLOGY Feb 2012 aeruginosa and Malassezia pachydermatis Results Lloyd et al. Vet Record, 1999 Antimicrobial efficacy of shampoos is highly variable. Compared 2-4% chlorhexidine shampoos

Only the chlorhexidine products had consistent broad- Results spectrum activity. 3% and 4% elimlinated Staph intermedius in <1 min at both 1:5 and 1:25 dilutions “Chloroxylenol and acetic acid/boric acid shampoos, in contrast, displayed little to no antibacterial activity” but had 2% elimlinated Staph intermedius at 1:5 and 1:25 dilutions at some effect against Malassezia 8 min

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Activity of chlorhexidine shampoo in vitro against Topical Therapy staphylococcus intermedius, Pseudomonas The right products for the right problem aeruginosa and Malassezia pachydermatis Lloyd et al. Vet Record, 1999 Antimicrobial Results – (continued) ◦ Antibacterial ◦ Chlorhexidine A 2% chlorhexidine shampoo showed faster bactericidal than Antibacterial a 2.5% ◦ Benzoyl peroxide Antifungal ◦ Acetic acid/Boric Acid Antiviral ◦ Ethyl lactate Some effect vs. Malassezia Indicates that formulation also influences efficacy ◦ Chloroxylenol

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Antimicrobial Antimicrobial ◦ Antibacterial ◦ Antibacterial ◦ Chlorhexidine ◦ Chlorhexidine Antibacterial ◦ Benzoyl peroxide ◦ Benzoyl peroxide Degreasing/ ◦ Acetic acid/Boric Acid ◦ Acetic acid/Boric Acid Follicular flushing ◦ Ethyl lactate ◦ Ethyl lactate ◦ Chloroxylenol ◦ Chloroxylenol Drying? – caution with >2.5%

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Antimicrobial Antimicrobial ◦ Antibacterial ◦ Antibacterial ◦ Chlorhexidine ◦ Chlorhexidine Mild Antibacterial ◦ Benzoyl peroxide ◦ Benzoyl peroxide Mild Antifungal ◦ Acetic acid/Boric Acid ◦ Acetic acid/Boric Acid ◦ Ethyl lactate ◦ Ethyl lactate ◦ Chloroxylenol ◦ Chloroxylenol

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Antimicrobial Antimicrobial ◦ Antibacterial ◦ Antibacterial ◦ Chlorhexidine ◦ Chlorhexidine ◦ Benzoyl peroxide ◦ Benzoyl peroxide ◦ Acetic acid/Boric Acid ◦ Acetic acid/Boric Acid ◦ Ethyl lactate ◦ Ethyl lactate ◦ Chloroxylenol ◦ Chloroxylenol

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Antimicrobial Antimicrobial ◦ Antibacterial ◦ Combination ◦ Chlorhexidine – Antibacterial/Antifungal ◦ Benzoyl peroxide ◦ Chlorhexidine/miconazole ◦ Acetic acid/Boric Acid ◦ Chlorhexidine/ ◦ Ethyl lactate ◦ Chloroxylenol/miconazole ◦ Chloroxylenol ◦ Addition of miconazole or ketoconazole for antifungal (anti-yeast) properties ◦ Significant improvement in management of Malassezia ◦ Role in bacterial infections…

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Antimicrobial Antimicrobial ◦ Combination ◦ Combination – Antibacterial/Antifungal

Miconahex+Triz – 2% Chlorhex, 2% miconazole, TrizEDTA, Ceramide complex (ceramides 1,3,6) ◦ Chlorhexidine/miconazole Mal-a-Ket – 2% Chlorhex, 1% ketoconaozle, 2% acetic acid ◦ Chlorhexidine/ketoconazole ◦ Chloroxylenol/miconazole Malaseb - 2% Chlorhex, 2% miconazole nitrate BioHex - 2% Chlorhexidine, 2% Miconazole w/MicroSilver and Ceramide III KetoSeb-D – 2% Chlorhexidine, 1% Ketoconazole KetoSeb PS - 2% Chlorhexidine, 1% Ketoconazole, 0.05% Phytosphingosine Sebozole - 1% Chloroxylenol, 2% Miconazole Nitrate Pharmaseb - 2.0% Chloroxylenol, 1.0% Ketoconazole

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Antiseborrheic Topical Therapy SCALE FOLLICULAR CASTS The right products for the right problem

Antiseborrheic shampoos ◦ Indications ◦ Primary seborrhea (cocker spaniels, springer spaniels, Irish setters) ◦ Secondary seborrhea (atopy, demodicosis) ◦ Schnauzer comedo syndrome ◦ Primary scaling disorders (sebaceous adenitis, follicular dysplasias) EXCESS SEBUM CRUST

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem Antiseborrheic Antiseborrheic - Mild ◦ Mild ◦ Benzoyl peroxide ◦ Moderate ◦ Phytosphingosine ◦ Aggressive ◦ Zinc gluconate ◦ disulfide

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Antiseborrheic - Mild Antiseborrheic - Mild ◦ Benzoyl peroxide ◦ Phytosphingosine ◦ Degreasing ◦ Sphingosine analog (ceramide) ◦ Hydrolyzes sebum ◦ Replaces key components of cornified cell ◦ Reduces sebaceous gland activity envelope that may be lacking in atopy and other skin diseases ◦ Follicular flushing ◦ Keratomdulating – effect on normalizing cell ◦ Keratolytic production rates ◦ Antibacterial

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Antiseborrheic - Mild Antiseborrheic - Moderate ◦ Selenium disulfide ◦ Salicylic acid ◦ Keratolytic and keratoplastic by reducing epidermal turnover ◦ Sulfur and impairing attachments between keratinocytes ◦ Caution – marked detergent, irritant and drying effects ◦ Combinations of ◦ Can result in a rebound increase in sebum production therefore ◦ Benzoyl peroxide + Sulfur/salicylic acid increased severity of seborrhea ◦ Chlorhexidine + sulfur salicylic acid ◦ Pyrithione zinc?

Typically not a great choice

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem

Antiseborrheic - Moderate Antiseborrheic – Moderate ◦ Salicylic acid ◦ Keratolytic ◦ Reduces skin pH increasing the amount of water the stratum corneum can absorb ◦ Direct effect on intercellular adhesions which softens the corneal layer ◦ Synergistic with sulfur – best when present in equal amts ◦ Sulfur ◦ Mildly keratolytic ◦ Keratoplastic ◦ Very drying

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Topical Therapy Topical Therapy The right products for the right problem The right products for the right problem Primary idiopathic seborrhea Antiseborrheic – Aggressive ◦ Tar ◦ Keratoplastic ◦ Reduces nuclear synthesis in the epidermal basal layer thereby reducing epidermal cell production/turnover rate ◦ Side effects (esp with higher conc) – drying, irritation, coat discoloration ◦ Possible carcinogen ◦ Rarely indicated ◦ Severe seborrhea such as primary idiopathic seborrhea of cocker spaniels

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Topical Therapy The right products for the right problem So what do you keep on the shelf? My advice Antiseborrheic – Aggressive Routine cleansing – 1 (+/-) ◦ Most no longer available Soothing/Antipruritic – 1 ◦ Use as last resort and often only after others have been Antibacterial – 1 or 2* utilized Antifungal or combination antifungal/antibacterial – 1 Antiseborrheic – mild – 1* Antiseborrheic – Moderate - 1

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Other topicals Other topicals

Sprays Sprays ◦Glucocorticoid ◦Glucocorticoid - Other options ◦ Gentocin/Betagen Topical Spray ◦ 1% Hydrocortisone ◦ Very long history of use ◦ Less concern for adverse effects ◦ Perceived as harmless by many ◦ Still use precautions as a corticosteroid ◦ Betamethasone - potent corticosteroid ◦ Potential adverse effects ◦ TrizChlor 4 HC ◦ Epidermal atrophy ◦ Malacetic Utra ◦ Systemic absorption ◦ Adrenal suppression

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Topical Sprays Topical Sprays

12 dogs Materials/Methods Normal - No Hx of skin disease ◦ Pre-bathed 3 days prior – Maintenance shampoo Various Breeds: Boston terrier, Australian shepherd, ◦ Day 0 – miniature schnauzer, Cavalier King Charles spaniel Two pumps sprayed per section and Pomeranian ◦ 4 active ingredient sprays ◦ 1 saline control

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Topical Sprays Topical Sprays

Materials/Methods Results ◦ 1% chlorhexidine digluconate SALINE 4% Chlorhexidine, TrizEDTA ◦ 2% miconazole, 2% chlorhexidine gluconate, TrizEDTA ◦ 3% chlorhexidine gluconate, phytosphingosine salicyloyl ◦ 4% chlorhexidine gluconate, TrizEDTA

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Topical Sprays Other topicals

Sprays ◦Antibacterial Results ◦ TrizChlor4 ◦ TrizChlor4 HC

◦Combination antibacterial/antifungal * ◦ MiconaHex Triz * ◦ Malacetic Ultra ◦ Malaseb

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Other topicals Other topicals Wipes Mousse/Foam – leave on ◦Antibacterial ◦ TrizChlor4

◦Combination antibacterial/antifungal ◦ MiconaHex Triz ◦ Malaseb ◦ Douxo PS chlorhexidine ◦ BioHex

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Special circumstances MRS_ Diluted Bleach

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An in vitro study to determine the minimal bactericidalbactericidal An in vitro study to determine the minimal bactericidalbactericidal concentration of sodium hypochlorite (bleach) required to concentration of sodium hypochlorite (bleach) required to inhibit meticillin-resistant Staphylococcus inhibit meticillin-resistant Staphylococcus pseudintermedius strains isolated from canine skin pseudintermedius strains isolated from canine skin Pariser et al, Vet Dermatol 2013; 24: 632–e157 Pariser et al, Vet Dermatol 2013; 24: 632–e157

11 MRSP isolates Results Incubated with serial dilutions of bleach to ◦ No growth in 9/11 at 1:64 dilution identify minimal bactericidal concentration (MBC) ◦ No growth in 11/11 at 1:32 dilution MBC = lowest concentration that prevented any bacterial Practical application growth in each of the three replications ◦ 1:64 dilution = ¼ cup bleach per gallon water ◦ 1:32 dilution = ½ cup bleach per gallon water

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In vitro evaluation of the use of diluted sodium hypochlorite (bleach) against Staphylococcus Diluted sodium hypochlorite (bleach) in dogs: antiseptic pseudintermedius , Pseudomonas aeruginosa and efficacy, local tolerability and in vitro effect on skin barrierbarrier Malassezia pachydermatis function and inflammation Banovic F, Lemo N, Vet Dermatol 2014; 25: 233–234 Banovic F, et al. Vet Dermatol 2017

MBC concentration of diluted bleach determined 0.05% dilution applied (1:20) and allowed to dry after 3 and 5 min for “There was no development of skin erythema or ◦ Staph. Pseudintermedius n=10 scaling after application of diluted bleach or ◦ Pseudomonas aeruinosa n=10 water on the thorax of any dogs (scores of “0” at ◦ Malassezia pachydermatis n=10 all times).” Results ◦ All isolates killed by 1:32 dilution at both contact times

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Diluted bleach Diluted bleach as an antimicrobial as an antimicrobial

Protocol Precautions ◦ Shampoo (4% Chlorhexidine) & RINSE THOROUGHLY ◦ Chlorhexidine + Bleach will cause brown precipitate and ◦ Diluted bleach leave-on rinse (or rinse after 5-10 min) discoloration. ◦ ¼ cup household bleach (6.15%) ◦ Unlikely to wash out of fabrics or fur mixed with 1 gallon water ◦ Increase to ½ cup per gallon water if needed and well tolerated ◦ Re-mix at least weekly ◦ Can be repeated without bathing 1-2 times per week. Watch for irritation/inflammation

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Conclusions/Suggestions…

If we choose products based on a knowledge of Better product advice based on science and disease/problem being treated and products proven clinical effect means better clinicians and available, everyone wins! better patient care!

Appropriate choice of products typically result in clients returning and requesting the product prescribed

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