Non Insecticidal Veterinary Shampoo Components
Content
Vol. 21, No. 1 January 1999
V
20TH ANNIVERSARY
CE
Refereed Peer Review
FOCAL POINT 5Knowledge of shampoo
ingredients and their uses and contraindications allows veterinarians to choose the most appropriate shampoo products for their patients.
Noninsecticidal Veterinary Shampoo Components
Texas A&M University
Christine A. Rees, DVM
ABSTRACT: The abundance of veterinary shampoos can make it difficult to decide which to choose for a particular patient. Becoming familiar with individual shampoo ingredients can make the decision easier. The chances of obtaining positive results from topical therapy are increased when tactile and visual findings, cytology results, and the primary concerns of owners are all considered. In addition, patients may benefit from a combination of several different topical therapies.
KEY FACTS
s Benzoyl peroxide is difficult to manufacture and breaks down with time; heeding expiration dates and purchasing these products from well-known, reputable companies is therefore advised. s Povidone–iodine has relatively short residual activity and is inactivated by organic debris. s Tar is an effective antiseborrheic agent because it has degreasing as well as keratoplastic properties. s A shampoo ingredient that was appropriate for a particular patient once may not be effective in the future.
N
oninsecticidal shampoos are an essential adjuvant therapy for treating small animal dermatologic conditions. However, the abundance of products (more than 100 are listed in the most recent edition of the Compendium of Veterinary Products1) can cause confusion about which is appropriate for a particular patient. The best way to deal with this situation is not to memorize all of the different products but to become familiar with the ingredients. There are six shampoo-ingredient categories based on mechanism of action, including antibacterial, antifungal, antiseborrheic, moisturizing, antipruritic (Table I), and residual-extending agents. The first four categories have been covered extensively in the literature and are therefore only briefly reviewed here.2–4 Clinical cases illustrate the practical application of the information discussed.
ANTIBACTERIAL INGREDIENTS The five main antibacterial shampoo ingredients are benzoyl peroxide, chlorhexidine, povidone–iodine, triclosan, and ethyl lactate. All are useful for treating surface and superficial bacterial skin infections2–4; only benzoyl peroxide, however, is useful for treating deep bacterial skin infections because of its ability to penetrate deep within hair follicles and sebaceous glands.2–3 Benzoyl Peroxide Benzoyl peroxide is an excellent antibacterial shampoo ingredient that has degreasing and antiseborrheic (keratolytic) properties.2 Its antibacterial action results from its ability to oxidize substances and has been shown to last for as long as 2 days.5 Precautions associated with benzoyl peroxide use are excessive drying and/or irritation of the skin and haircoat, bleaching of fabrics, odor, and lack of
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TABLE I Small Animal Shampoo-Ingredient Information Activity a Ingredient Aloe vera Benzoyl peroxide Degreasing Antibacterial Antifungal – Antipruritic Keratolytic Keratoplastic Side Effects and Precautions – Drying, minimal lather, irritating to skin, bleaching; watch expiration dates, use reputable companies – – Staining, irritating to skin – – – Drying, staining, irritating to skin Odor, stains jewelry and light-coated animalsd Drying, staining, odor, irritating to skin, photosensitive, superficial necrolytic dermatitis –
+
–
+
–
+
+ +
–
– –
+
Chlorhexidine Ethyl lactate Iodine Miconazole Oatmealb Salicylic acid Selenium sulfidec Sulfur Tarc
– – – – – –
+ + +
– –
+
–
– – – –
– – – – –
– – – – –
+ +
– –
+
–
+ +
–
+
–
+ +d
–
+ + + +
+ + + +
+
–
+d
–
+
Triclosan
aResidual-extending bOatmeal
–
+
–
–
–
–
agents do not provide any of these properties and are thus not included. shampoos may contain additional antipruritic agents, such as topical anesthetics (e.g., pramoxine), antihistamines (e.g., diphenhydramine), and cortisone (e.g., hydrocortisone), or oatmeal alone. c Tar and selenium sulfide should not be used in cats because they are too irritating to feline skin. d These effects are only seen with sulfur dip.
latherability. Benzoyl peroxide is difficult to manufacture and breaks down with time; heeding expiration dates and purchasing these products from well-known, reputable companies is therefore advised.2 Excessive drying may be avoided by using a moisturizing spray or conditioner after benzoyl peroxide application.
also known for its residual properties, lasting as long as 2 days.5,6 No specific precautions have been documented at shampoo concentrations (4% or less). This product is nonirritating, nontoxic, and well tolerated.
Chlorhexidine Chlorhexidine is a synthetic biguanide with antibacterial, antifungal, and antiviral activities.5,6 It exerts its antibacterial effects by acting on the bacterial cell membrane, precipitating intracellular contents, and inhibiting ATP.7,8 Chlorhexidine differs from iodine-containing products in that it is not inhibited or inactivated by organic debris (e.g., dirt, scale, crust).6 Chlorhexidine is
Povidone–Iodine Povidone–iodine is an antibacterial agent with antifungal, antiviral, and antiprotozoal activity 9,10 that works by iodinating and oxidizing sulfhydryl compounds, peptides, proteins, enzymes, vitamins, lipids, and cytosine found in the cytoplasm and cytoplasmic membranes.10,11 Unlike chlorhexidine, povidone–iodine has relatively short residual activity (4 to 6 hours) and is inactivated by organic debris (e.g., dirt, crust, scale).6,12 The main precautions associated with povi-
EXCESSIVE DRYING s ORGANIC DEBRIS s RESIDUAL PROPERTIES
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done–iodine use are contact dermatitis, skin irritation, and staining.6,8,12
Triclosan Triclosan is an antibacterial agent that is added into antiseborrheic shampoos to extend their spectrum of activity (i.e., provide more antibacterial properties). Triclosan produces its effects by causing loss of plasmamembrane integrity and cell death through apoptosis in vitro.13 Allergic contact dermatitis may occur.14 Ethyl Lactate Ethyl lactate is an antibacterial agent that penetrates hair follicles and sebaceous glands but has no proven benefits in treating deep pyoderma.15 This ingredient becomes effective by breaking down into two compounds within the skin, lactic acid and ethanol. Lactic acid acts by decreasing the skin’s pH and thus inhibiting bacterial lipases,5 whereas ethanol renders fats soluble and decreases the amount of sebaceous secretions.4 Side effects (e.g., irritation, erythema, pruritus) are infrequent.14 ANTIFUNGAL INGREDIENTS The three main shampoo ingredients known for their antifungal properties are miconazole, chlorhexidine, and povidone–iodine. The latter two ingredients have been discussed previously. Miconazole Miconazole is an imidazole derivative that exerts its antifungal properties by inhibiting ergosterol synthesis.15 Ergosterol is an essential component of the fungal cell membrane. Inhibition of ergosterol synthesis results in fungal cell death.15 No specific side effects have been documented with miconazole shampoo formulations. ANTISEBORRHEIC INGREDIENTS Seborrhea is an imbalance in the skin’s keratinization process in which skin cells (keratinocytes) tend to turn over more rapidly than usual, resulting in excessive scaling and crusting of the skin. The purpose of antiseborrheic ingredients is to try to normalize this process by working at the skin’s surface to remove the excess scale (keratolytic properties) and at the basal layer to slow cell turnover (keratoplastic properties).2,3,5 The two different forms of seborrhea are seborrhea oleosa (oily form) and seborrhea sicca (dry form).2 It is important to quantify the type of seborrhea that is present because different shampoo ingredients are used for each condition. A degreasing agent with antiseborrheic properties is required to gain the most effective control of seborrhea oleosa. The two ingredients with excellent degreasing
properties are benzoyl peroxide (discussed previously) and tar.2 Seborrhea sicca is most commonly treated with sulfur and salicylic acid combination shampoos. Sulfur and salicylic acid have been shown to act synergistically to help remove scale.16 At shampoo concentrations (i.e., 2% to 3%), these products are safe for use in dogs and cats. If the amount of scaling is minimal, a moisturizing spray or shampoo may be effective (see Moisturizing Ingredients below).
Tar Tar is an effective antiseborrheic agent because it not only degreases but also has keratoplastic properties. Tar has been shown to slow skin-cell turnover by suppressing DNA synthesis at the basal layer.2 Other properties include its ability to produce vasoconstriction and decrease pruritus.2,3 Precautions associated with the topical use of tar include unpleasant color (brown) and odor, skin irritation, excessive drying of skin and haircoat, photosensitization, and superficial necrolytic dermatitis.2,3,5,17 Tar is not approved for use in cats because it is extremely irritating to their skin.2 In addition, because tar production techniques and refinement may affect its efficacy, tar shampoos should be purchased only from reputable companies.2,5 Sulfur Sulfur is reportedly both keratoplastic and keratolytic. The keratoplastic properties are thought to result from either the drug’s cytostatic capabilities or its reaction with cysteine in the skin to form cystine and hydrogen sulfide (building blocks for normal keratinization). Sulfur’s keratolytic properties, which result from excess hydrogen sulfide formation, have been detected at high concentrations.2 Salicylic Acid Salicylic acid is also keratoplastic and keratolytic; these effects are produced by decreasing the skin’s pH, which increases the hydration of the keratin and causes swelling of the stratum corneal cells. Salicylic acid also solubilizes the intercellular cement substance that holds the scale together.2 MOISTURIZING INGREDIENTS Moisturizing ingredients help to rehydrate the skin and restore it to a more normal state.2,5 Almost all veterinary shampoos contain one or more of these ingredients. Moisturizing products have not been associated with any side effects when used at the recommended shampoo ingredient concentrations. The two main groups of moisturizing ingredients include humectants and emollients/emulsifying agents.
KERATINIZATION s SEBORRHEA s VASOCONSTRICTION s REHYDRATION
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Humectants Humectants act to rehydrate the skin by attracting water from deep within the skin toward the surface. These ingredients are non-oily. Examples include natural moisturizing factors (e.g., carboxylic acid, lactic acid, urea), sodium lactate, propylene glycol, glycerin, and polyvinylpyrrolidone.2 Emollients/Emulsifiers Emollients and emulsifiers act by filling in the spaces between keratinocytes with oil. Examples of emollients include oils (e.g., almond, corn, cottonseed, coconut, olive, peanut, persia, safflower, sesame), animal fats (e.g., lanolin [sheep wool]), and hydrocarbons (e.g., mineral oil, paraffin, petrolatum2). Emulsifiers are often added to emollient solutions to help distribute the oils into a water solution; this makes the oil solution more effective because it can spread more evenly over the skin’s surface. Examples of emulsifiers include cetyl alcohol, laureth-5, lecithin, PEG-4 dilaurate, stearic acid, and stearyl alcohol.2 ANTIPRURITIC INGREDIENTS Oatmeal and aloe vera are added to veterinary shampoos specifically for their antipruritic activities.18,19 The antipruritic activity of other shampoo ingredients (discussed in the text and Table I) probably results from antibacterial properties.2–4 Oatmeal The use of oatmeal in topical preparations evolved from its use in folk medicine, which advocates homemade topical oatmeal preparations to soothe irritated skin for as long as 2 days.18,20 The exact mechanism of action is unknown, but one report suggests that oatmeal inhibits prostaglandin biosynthesis.21 The only side effect reported with topical oatmeal use is allergic contact dermatitis in humans.22 A recent double-blinded study concluded, however, that topical oatmeal did not induce allergic contact dermatitis in normal or atopic children.23 Aloe Vera The stabilized viscous juice from the inner part of aloe vera leaves is used to produce topical preparations. This juice has antipruritic, healing properties as well as antibacterial and antifungal properties in vitro.19 Salicylic acid and magnesium lactate are the two chemical compounds within topical aloe preparations that produce its antipruritic effects.18 The mechanisms of action of these ingredients differ. Salicylic acid inhibits the production of prostaglandin from arachidonic acid by inhibiting cyclooxygenase,24 whereas magne-
sium lactate has been shown to inhibit the conversion of histidine to histamine in mast cells via an enzyme called histidine carboxylase.25 Aloe vera is thought to produce its healing properties by increasing dermal perfusion and decreasing inflammatory mediators (e.g., thromboxane, prostaglandin) in burn lesions.18 The exact concentration necessary to produce healing effects in a shampoo preparation is unknown. Side effects include the production of an eczematous, papular dermatitis in humans.26 Side effects from topical aloe vera use in animals have not been documented.
RESIDUAL-EXTENDING INGREDIENTS Novosomes® Novosomes® (Evasco Pharmaceuticals, Buena, NJ) are extremely stable, specially formulated nonphospholipid microvesicles (i.e., a type of liposome) with five to seven bilayers and a central holding area, 80% of which is comprised of water and/or lipids.27 Novosomes® (approximately 5 µm in diameter) are not susceptible to degradation by hydrolytic enzymes and are stable at temperatures as high as 80˚C. They have increased resistance to the autooxidative process when compared with regular liposomes.27 The particle charge on Novosomes® is formulated to tightly adhere to the skin and hair. The inner solution within the cargo area is slowly released as the various layers break down (requiring 7 to 10 days in average temperature conditions).27 Spherulites® Spherulites® (Allerderm/Virbac, Fort Worth, TX) are composed of multiple layers (10 to 1000) of plant-derived surfactants and are 1 µm in diameter. Spherulites® contain chitosanide—a multipurpose glycoprotein derived from chitin (crustacean shells)—which helps to form a film coating over the skin and hair, as well as an additional shampoo ingredient. Chitosanide also tightly binds the Spherulites® to the hair and skin by providing chemical differences in positive and negative charges. The shampoo ingredient within the Spherulites® is slowly released (over 8 days) as the different layers of the Spherulite® break down. Moisturizing agents, essential oils, and water- and fat-soluble vitamins can all be encapsulated in the same Spherulite®.28 CASE EXAMPLES Case 1 Signalment and History A 2-year-old, spayed female Chihuahua was presented to the Texas Veterinary Medical Center with generalized scaling and a 1-year history of nonseasonal moderate
SALICYLIC ACID s MAGNESIUM LACTATE s MICROVESICLES s CHITOSANIDE
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Diagnosis and Treatment The diagnosis for this dog Physical Examination was atopy and seborrhea sicPhysical examination reca with a secondary bacterial vealed multifocal areas of skin and ear infection. The alopecia on the dog’s face, topical treatment used in shoulders, legs, neck, and Figure 1—Alopecia, lichenification, and mild erythema on this case was a shampoo ventrum (Figure 1). The skin the ventral cervical area of a dog. containing a chlorhexidine was erythematous, licheniand sulfur/salicylic acid fied, and dry with moderate combination with a residuamounts of scale. Both ears al-extending agent (Novowere slightly erythematous somes®). The antibacterial properwith a mild ceruminous disties of chlorhexidine were charge. beneficial for treating the Differential Diagnoses pyoderma, the sulfur/salicylic The main differential diacid combination aided in agnoses for this case were removing scale, and the food hypersensitivity, allerNovosomes ® extended the rehydrating properties of the gic dermatitis secondary to bath. Other appropriate atopy, and allergic contact choices for this case includdermatitis. Other differential diagnoses included bac- Figure 2—Intradermal skin test reactions on the lateral thorax ed using a sulfur/salicylic acid and triclosan shampoo, terial skin infection, fungal of a dog. an ethyl lactate shampoo skin infection, demodicosis, Malassezia dermatitis, and with a residual-extending seborrhea sicca (primary or secondary). The degree of agent (Spherulites®), or a benzoyl peroxide shampoo with Novosomes®. A leave-on conditioner containing pruritus and distribution of lesions helped to eliminate oatmeal and pramoxine was prescribed as a topical scabies from the differential diagnosis list. Because pruagent to help relieve the pruritus; any of the topical ritus was not exacerbated on food rechallenge, a diagoatmeal conditioners or sprays would have been appronosis of food allergy was less likely. The distribution of priate to use in this case. Other medications used in lesions and the history were not consistent with a diagthis case included gentamicin sulfate otic (three drops nosis of contact allergy. Atopy was therefore the most in both ears every 12 hours for 14 days), lincomycin probable underlying cause for this case. The other dif(22 mg/kg every 12 hours for 21 days), hyposensitizaferential diagnoses were ruled out with diagnostic tests. tion vaccines, and hydroxyzine (2.2 mg/kg every 8 Diagnostic Tests hours for 14 days). Several diagnostic tests were performed to reach the Case 2 diagnosis. Multiple skin scrapings were negative for ecSignalment and History toparasites. Impression smears of the skin revealed nuA 10-year-old, intact, male English springer spaniel merous surface cocci around and within keratinocytes was presented at the Texas Veterinary Medical Center (more than 40 per high-power field). Ear-swab cytology with a 6-year history of oily, scaling, thickened skin revealed inflammatory cells (neutrophils) and cocci with alopecia on the dorsum of all four feet, backs of bacteria. Chlorphenolac preparations and dermatoFOOD-ELIMINATION DIET s SKIN SCRAPINGS s CYTOLOGY s ATOPY
pruritus that was sometimes present without dermatologic lesions. The patient was put on a food-elimination diet for 3 months using a commercially prepared venison and potato diet. No increase in pruritus was noted when the original diet was reinstituted.
phyte test media cultures were negative for dermatophytes. An intradermal skin test had numerous positive reactions (grasses, weeds, trees, molds, and house dust mites; Figure 2).
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the ears, caudal thighs, and lateral thorax. This dermatologic condition was mildly pruritic and nonseasonal. Previous treatment included oral and injectable steroids, various antibiotics, and ketoconazole (unknown dose and frequency). According to the owner, steroids, cephalexin, and ketoconazole had somewhat improved the dog’s condition in the past. The dog was fed a commercially prepared Figure 3—Alopecia, lichenification, erythema, crust, and scale along the back of the left pinna of a dog. lamb and rice diet.
biopsy showed evidence of superficial pyoderma with an underlying allergy. The complete blood count showed evidence of eosinophilia, which was thought to be associated with an internal or external parasite load; however, a fecal examination and occult heartworm test were negative for parasites. The urinalysis had abnormal amounts of bacteria, and neutrophils revealed cystitis.
Diagnosis and Treatment The diagnosis for this dog was seborrhea oleosa, allergic dermatitis, and otitis externa with a secondary bacterial skin infection. Topical therapy consisted of twice-weekly baths with a benzoyl peroxide shampoo followed by a leave-on chlorhexidine cream rinse for the superficial pyoderma. Benzoyl peroxide was chosen in this case because Figure 4—Alopecia, lichenification, erythema, and excoriation on the dog had oily skin with a the left lateral stifle of a dog. secondary infection. (A 2% Differential Diagnoses tar shampoo would be an Several differential diagnoses were considered, inappropriate alternative therapy because it is also a cluding allergic dermatitis (e.g., food allergy, atopy, good degreasing agent.) A chlorhexidine leave-on concontact allergy, flea hypersensitivity), ectoparasites (e.g., ditioner was selected because it rehydrates the skin scabies, demodicosis), and a secondary skin infection and provides some secondary residual antibacterial ef(e.g., bacterial, fungal). Although the ears and stifle arfects. Any moisturizing agent would be appropriate eas were involved, the possibility of scabies was low beand was considered necessary because benzoyl peroxcause pruritus was mild and the condition was present ide tends to be drying. The otitis externa was treated for a relatively short time (6 years). with gentamicin sulfate otic (three drops every 12 hours for 14 days). A commercially prepared duck Diagnostic Tests and potato diet was prescribed for an 8-week eliminaMultiple skin scrapings were negative for ectoparation diet. sites. Impression smears of the skin and crust revealed The dog was markedly improved at the end of the 8numerous cocci and some neutrophils and macroweek food trial (pruritus decreased more than 50%). At phages (more than 30 per high-power field). Numerous the conclusion of the trial, rechallenge with the dog’s cocci bacteria and neutrophils were noted on the earold food confirmed food allergy (pruritus increased swab cytology. Otoscopic examination of both ears remore than 50% within several days of food rechalvealed patent ears with intact tympanic membranes. lenge). Challenging the dog with individual food ingreChlorphenolac preparation and dermatophyte test medients revealed allergies to beef, egg, wheat, soy, and dia cultures were negative for dermatophytes. Skin chicken. Physical Examination Physical examination revealed several dermatologic abnormalities, including alopecia, erythema, lichenification, excess scale, and some crusts on the face, caudal aspect of both pinnae (Figure 3), ventral neck and ventrum, and extremities (especially the stifles and dorsum of the feet; Figure 4). The canals of both ears were erythematous with a ceruminous discharge.
CHLORPHENOLAC PREPARATION s EOSINOPHILIA s FOOD ALLERGY
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Small Animal/Exotics
DISCUSSION Both of the patients discussed in the case examples had bacterial pyoderma and allergy, but they were treated with different topical therapies because their skin and hair had different tactile properties. The dog in the first case had dry scale that required a moisturizing keratolytic and keratoplastic agent, whereas the second dog had oily scale requiring a degreasing and keratolytic agent. The main complaint of the first dog’s owner was pruritus, thus a leave-on oatmeal with pramoxine conditioner was selected. The history of pruritus without any evidence of dermatologic lesions suggested that allergy was a reasonable differential diagnosis. The haircoat and skin of the second dog were oily and the dog was mildly pruritic, thus a degreasing shampoo (benzoyl peroxide) and leave-on chlorhexidine conditioner were considered appropriate therapy. Systemic antibiotics were used in addition to the topical therapy to treat the skin infection. Recheck visits help determine whether antibiotics have been administered for an appropriate length of time (minimum of 3 weeks). As in the first case, the dog in case 2 was still pruritic even though the pyoderma was cleared. This clinical information along with the biopsy results indicated that food allergy was a reasonable differential diagnostic concern. These cases demonstrate that tactile and visual findings, cytology results, and the owners’ primary concerns should be considered when selecting topical therapy to maximize a patient’s chance of benefiting from it. As was done in these cases, owners should also be informed that their pets’ skin condition could change with time and thus a shampoo or conditioner that was once appropriate may not be in the future. Finally, these cases demonstrate that more than one topical therapy may be appropriate for a particular patient. About the Author
Dr. Rees is affiliated with the Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, Texas. She is a Diplomate of the American College of Veterinary Dermatology.
REFERENCES
1. Compendium of Veterinary Products, ed 4. Port Huron, MI, North American Compendium Inc, 1995–1996, p 1300. 2. Kwochka KW: Symptomatic topical therapy of scaling disorders, in Griffin CE, Kwochka KW, MacDonald JM (eds): Current Veterinary Dermatology. St Louis, Mosby–Year Book, 1993, pp 191–202. 3. Scheidt VJ: The basic principles of shampoo therapy. Vet Focus 2(2):58–61, 1990.
4. Ascher F, Maynard L, Laurent J, Goubet B: Controlled trial of ethyl lactate and benzoyl peroxide shampoos in the management of canine surface pyoderma and superficial pyoderma, in von Tscharner C, Halliwell REW (eds): Advances in Veterinary Dermatology, ed 1. London, Bailliere Tindall, 1990, pp 375–382. 5. Scott DW, Miller WH, Griffin CE: Dermatologic therapy, in Muller and Kink’s Small Animal Dermatology, ed 5. Philadelphia, WB Saunders Co, 1995, pp 174–277. 6. Sebben JE: Surgical antiseptics. J Am Acad Dermatol 9(5): 759–765, 1993. 7. Sanchez IR, Nusbaum KE, Swaim SF, et al: Chlorhexidine diacetate and povidone–iodine cytotoxicity to canine embryonic fibroblasts and Staphylococcus aureus. Vet Surg 17(4): 182–185, 1988. 8. Lozier SM: Topical wound therapy, in Harari J (ed): Surgical Complications and Wound Healing in the Small Animal Practice. Philadelphia, WB Saunders Co, 1993, pp 63–88. 9. Zamora JL: Povidone–iodine and wound infection. Surgery 95:121–122, 1984. 10. Zamora JL: Chemical and microbiologic characteristics and toxicity of povodone–iodine solutions. Am J Surg 151: 400–406, 1984. 11. Swaim SF, Lee AH: Topical wound medications: A review. JAVMA 190(10):1588–1593, 1987. 12. Osuna DJ, DeYoung DJ, Walker RL, et al: Comparison of three skin preparation techniques in the dog. Part 2. Clinical trial in 100 dogs. Vet Surg 19(1)20–23, 1990. 13. Zuckerraun HL, Babich H, May R, Sinensky MC: Triclosan: Cytotoxicity, mode of action, and induction of apoptosis in human gingival cells in vitro. Part 1. Eur J Oral Sci 106:628–636, 1998. 14. Kwochka KW: Rational shampoo therapy in veterinary dermatology. Proc 11th Annu Kal Kan Symp Treat Small Anim Dis:87, 1998. 15. Jawetz E: Antifungal agents, in Katzung BG (ed): Basic and Clinical Pharmacology. Los Altos, CA, Appleton and Lange, 1987, pp 554–558. 16. Leyden JJ, McGinley KJ, Mills OH, et al: Effects of sulfur and salicylic acid in a shampoo base in the treatment of dandruff: A double-blind study using counts and clinical grading. Cutis 39:557,1987. 17. Rosenkrantz WS, Griffin CE, Walder E, et al: Superficial suppurative necrolytic dermatitis in miniature schnauzers: A retrospective analysis. Proc ACVD/AAVD: 99, 1991. 18. Basset NG (ed): Herbal Drugs and Phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994, pp 96–98. 19. Klein AD, Penneys NS: Aloe vera. J Am Acad Dermatol 18:714–720, 1988. 20. Haliwell REW: The use of shampoos in veterinary practice. Vet Annu 36:127–141, 1996. 21. Saeed SA, Butt NM, McDonald-Gibson WJ, et al: Inhibitor(s) of prostaglandin biosynthesis in extracts of oat (Avena sativa) seeds. Biochem Soc Trans 9(5): 444, 1981. 22. Riboldi A, Pigatto PO, Altomare GF, et al: Contact allergic dermatitis from oatmeal. Contact Dermatitis 18(5): 316– 317, 1988. 23. Pigatto P, Bigardi A, Caputo R, et al: An evaluation of allergic contact dermatitis potential of colloidal grain suspen-
SYSTEMIC ANTIBIOTICS s OWNERS’ CONCERNS
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sions. Am J Contact Dermatol 8(4):207–209, 1997. 24. Moore PK, Hoult GR: Selective actions of aspirin and sulfasalazine-like compounds against prostaglandin synthesis and breakdown. Biochem Pharmacol 31:969–971, 1982. 25. Lehninger A (ed): Biochemistry, ed 2. New York, Worth, 1981, p 578.
26. Morrow DM, Rapaport MS, Strick RA: Hypersensitivity to aloe. Arch Dermatol 116:1064–1065, 1980. 27. Corll D: Novosomes® vs. liposomes. Evasco Pharmaceutic Newslet 1:1–2, 1998. 28. Koch HJ: Spherulites® Technical File. Fort Worth, TX, Allerderm/Virbac, 1998, pp 1–33.
V
20TH ANNIVERSARY
CE
Refereed Peer Review
FOCAL POINT 5Knowledge of shampoo
ingredients and their uses and contraindications allows veterinarians to choose the most appropriate shampoo products for their patients.
Noninsecticidal Veterinary Shampoo Components
Texas A&M University
Christine A. Rees, DVM
ABSTRACT: The abundance of veterinary shampoos can make it difficult to decide which to choose for a particular patient. Becoming familiar with individual shampoo ingredients can make the decision easier. The chances of obtaining positive results from topical therapy are increased when tactile and visual findings, cytology results, and the primary concerns of owners are all considered. In addition, patients may benefit from a combination of several different topical therapies.
KEY FACTS
s Benzoyl peroxide is difficult to manufacture and breaks down with time; heeding expiration dates and purchasing these products from well-known, reputable companies is therefore advised. s Povidone–iodine has relatively short residual activity and is inactivated by organic debris. s Tar is an effective antiseborrheic agent because it has degreasing as well as keratoplastic properties. s A shampoo ingredient that was appropriate for a particular patient once may not be effective in the future.
N
oninsecticidal shampoos are an essential adjuvant therapy for treating small animal dermatologic conditions. However, the abundance of products (more than 100 are listed in the most recent edition of the Compendium of Veterinary Products1) can cause confusion about which is appropriate for a particular patient. The best way to deal with this situation is not to memorize all of the different products but to become familiar with the ingredients. There are six shampoo-ingredient categories based on mechanism of action, including antibacterial, antifungal, antiseborrheic, moisturizing, antipruritic (Table I), and residual-extending agents. The first four categories have been covered extensively in the literature and are therefore only briefly reviewed here.2–4 Clinical cases illustrate the practical application of the information discussed.
ANTIBACTERIAL INGREDIENTS The five main antibacterial shampoo ingredients are benzoyl peroxide, chlorhexidine, povidone–iodine, triclosan, and ethyl lactate. All are useful for treating surface and superficial bacterial skin infections2–4; only benzoyl peroxide, however, is useful for treating deep bacterial skin infections because of its ability to penetrate deep within hair follicles and sebaceous glands.2–3 Benzoyl Peroxide Benzoyl peroxide is an excellent antibacterial shampoo ingredient that has degreasing and antiseborrheic (keratolytic) properties.2 Its antibacterial action results from its ability to oxidize substances and has been shown to last for as long as 2 days.5 Precautions associated with benzoyl peroxide use are excessive drying and/or irritation of the skin and haircoat, bleaching of fabrics, odor, and lack of
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TABLE I Small Animal Shampoo-Ingredient Information Activity a Ingredient Aloe vera Benzoyl peroxide Degreasing Antibacterial Antifungal – Antipruritic Keratolytic Keratoplastic Side Effects and Precautions – Drying, minimal lather, irritating to skin, bleaching; watch expiration dates, use reputable companies – – Staining, irritating to skin – – – Drying, staining, irritating to skin Odor, stains jewelry and light-coated animalsd Drying, staining, odor, irritating to skin, photosensitive, superficial necrolytic dermatitis –
+
–
+
–
+
+ +
–
– –
+
Chlorhexidine Ethyl lactate Iodine Miconazole Oatmealb Salicylic acid Selenium sulfidec Sulfur Tarc
– – – – – –
+ + +
– –
+
–
– – – –
– – – – –
– – – – –
+ +
– –
+
–
+ +
–
+
–
+ +d
–
+ + + +
+ + + +
+
–
+d
–
+
Triclosan
aResidual-extending bOatmeal
–
+
–
–
–
–
agents do not provide any of these properties and are thus not included. shampoos may contain additional antipruritic agents, such as topical anesthetics (e.g., pramoxine), antihistamines (e.g., diphenhydramine), and cortisone (e.g., hydrocortisone), or oatmeal alone. c Tar and selenium sulfide should not be used in cats because they are too irritating to feline skin. d These effects are only seen with sulfur dip.
latherability. Benzoyl peroxide is difficult to manufacture and breaks down with time; heeding expiration dates and purchasing these products from well-known, reputable companies is therefore advised.2 Excessive drying may be avoided by using a moisturizing spray or conditioner after benzoyl peroxide application.
also known for its residual properties, lasting as long as 2 days.5,6 No specific precautions have been documented at shampoo concentrations (4% or less). This product is nonirritating, nontoxic, and well tolerated.
Chlorhexidine Chlorhexidine is a synthetic biguanide with antibacterial, antifungal, and antiviral activities.5,6 It exerts its antibacterial effects by acting on the bacterial cell membrane, precipitating intracellular contents, and inhibiting ATP.7,8 Chlorhexidine differs from iodine-containing products in that it is not inhibited or inactivated by organic debris (e.g., dirt, scale, crust).6 Chlorhexidine is
Povidone–Iodine Povidone–iodine is an antibacterial agent with antifungal, antiviral, and antiprotozoal activity 9,10 that works by iodinating and oxidizing sulfhydryl compounds, peptides, proteins, enzymes, vitamins, lipids, and cytosine found in the cytoplasm and cytoplasmic membranes.10,11 Unlike chlorhexidine, povidone–iodine has relatively short residual activity (4 to 6 hours) and is inactivated by organic debris (e.g., dirt, crust, scale).6,12 The main precautions associated with povi-
EXCESSIVE DRYING s ORGANIC DEBRIS s RESIDUAL PROPERTIES
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done–iodine use are contact dermatitis, skin irritation, and staining.6,8,12
Triclosan Triclosan is an antibacterial agent that is added into antiseborrheic shampoos to extend their spectrum of activity (i.e., provide more antibacterial properties). Triclosan produces its effects by causing loss of plasmamembrane integrity and cell death through apoptosis in vitro.13 Allergic contact dermatitis may occur.14 Ethyl Lactate Ethyl lactate is an antibacterial agent that penetrates hair follicles and sebaceous glands but has no proven benefits in treating deep pyoderma.15 This ingredient becomes effective by breaking down into two compounds within the skin, lactic acid and ethanol. Lactic acid acts by decreasing the skin’s pH and thus inhibiting bacterial lipases,5 whereas ethanol renders fats soluble and decreases the amount of sebaceous secretions.4 Side effects (e.g., irritation, erythema, pruritus) are infrequent.14 ANTIFUNGAL INGREDIENTS The three main shampoo ingredients known for their antifungal properties are miconazole, chlorhexidine, and povidone–iodine. The latter two ingredients have been discussed previously. Miconazole Miconazole is an imidazole derivative that exerts its antifungal properties by inhibiting ergosterol synthesis.15 Ergosterol is an essential component of the fungal cell membrane. Inhibition of ergosterol synthesis results in fungal cell death.15 No specific side effects have been documented with miconazole shampoo formulations. ANTISEBORRHEIC INGREDIENTS Seborrhea is an imbalance in the skin’s keratinization process in which skin cells (keratinocytes) tend to turn over more rapidly than usual, resulting in excessive scaling and crusting of the skin. The purpose of antiseborrheic ingredients is to try to normalize this process by working at the skin’s surface to remove the excess scale (keratolytic properties) and at the basal layer to slow cell turnover (keratoplastic properties).2,3,5 The two different forms of seborrhea are seborrhea oleosa (oily form) and seborrhea sicca (dry form).2 It is important to quantify the type of seborrhea that is present because different shampoo ingredients are used for each condition. A degreasing agent with antiseborrheic properties is required to gain the most effective control of seborrhea oleosa. The two ingredients with excellent degreasing
properties are benzoyl peroxide (discussed previously) and tar.2 Seborrhea sicca is most commonly treated with sulfur and salicylic acid combination shampoos. Sulfur and salicylic acid have been shown to act synergistically to help remove scale.16 At shampoo concentrations (i.e., 2% to 3%), these products are safe for use in dogs and cats. If the amount of scaling is minimal, a moisturizing spray or shampoo may be effective (see Moisturizing Ingredients below).
Tar Tar is an effective antiseborrheic agent because it not only degreases but also has keratoplastic properties. Tar has been shown to slow skin-cell turnover by suppressing DNA synthesis at the basal layer.2 Other properties include its ability to produce vasoconstriction and decrease pruritus.2,3 Precautions associated with the topical use of tar include unpleasant color (brown) and odor, skin irritation, excessive drying of skin and haircoat, photosensitization, and superficial necrolytic dermatitis.2,3,5,17 Tar is not approved for use in cats because it is extremely irritating to their skin.2 In addition, because tar production techniques and refinement may affect its efficacy, tar shampoos should be purchased only from reputable companies.2,5 Sulfur Sulfur is reportedly both keratoplastic and keratolytic. The keratoplastic properties are thought to result from either the drug’s cytostatic capabilities or its reaction with cysteine in the skin to form cystine and hydrogen sulfide (building blocks for normal keratinization). Sulfur’s keratolytic properties, which result from excess hydrogen sulfide formation, have been detected at high concentrations.2 Salicylic Acid Salicylic acid is also keratoplastic and keratolytic; these effects are produced by decreasing the skin’s pH, which increases the hydration of the keratin and causes swelling of the stratum corneal cells. Salicylic acid also solubilizes the intercellular cement substance that holds the scale together.2 MOISTURIZING INGREDIENTS Moisturizing ingredients help to rehydrate the skin and restore it to a more normal state.2,5 Almost all veterinary shampoos contain one or more of these ingredients. Moisturizing products have not been associated with any side effects when used at the recommended shampoo ingredient concentrations. The two main groups of moisturizing ingredients include humectants and emollients/emulsifying agents.
KERATINIZATION s SEBORRHEA s VASOCONSTRICTION s REHYDRATION
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Humectants Humectants act to rehydrate the skin by attracting water from deep within the skin toward the surface. These ingredients are non-oily. Examples include natural moisturizing factors (e.g., carboxylic acid, lactic acid, urea), sodium lactate, propylene glycol, glycerin, and polyvinylpyrrolidone.2 Emollients/Emulsifiers Emollients and emulsifiers act by filling in the spaces between keratinocytes with oil. Examples of emollients include oils (e.g., almond, corn, cottonseed, coconut, olive, peanut, persia, safflower, sesame), animal fats (e.g., lanolin [sheep wool]), and hydrocarbons (e.g., mineral oil, paraffin, petrolatum2). Emulsifiers are often added to emollient solutions to help distribute the oils into a water solution; this makes the oil solution more effective because it can spread more evenly over the skin’s surface. Examples of emulsifiers include cetyl alcohol, laureth-5, lecithin, PEG-4 dilaurate, stearic acid, and stearyl alcohol.2 ANTIPRURITIC INGREDIENTS Oatmeal and aloe vera are added to veterinary shampoos specifically for their antipruritic activities.18,19 The antipruritic activity of other shampoo ingredients (discussed in the text and Table I) probably results from antibacterial properties.2–4 Oatmeal The use of oatmeal in topical preparations evolved from its use in folk medicine, which advocates homemade topical oatmeal preparations to soothe irritated skin for as long as 2 days.18,20 The exact mechanism of action is unknown, but one report suggests that oatmeal inhibits prostaglandin biosynthesis.21 The only side effect reported with topical oatmeal use is allergic contact dermatitis in humans.22 A recent double-blinded study concluded, however, that topical oatmeal did not induce allergic contact dermatitis in normal or atopic children.23 Aloe Vera The stabilized viscous juice from the inner part of aloe vera leaves is used to produce topical preparations. This juice has antipruritic, healing properties as well as antibacterial and antifungal properties in vitro.19 Salicylic acid and magnesium lactate are the two chemical compounds within topical aloe preparations that produce its antipruritic effects.18 The mechanisms of action of these ingredients differ. Salicylic acid inhibits the production of prostaglandin from arachidonic acid by inhibiting cyclooxygenase,24 whereas magne-
sium lactate has been shown to inhibit the conversion of histidine to histamine in mast cells via an enzyme called histidine carboxylase.25 Aloe vera is thought to produce its healing properties by increasing dermal perfusion and decreasing inflammatory mediators (e.g., thromboxane, prostaglandin) in burn lesions.18 The exact concentration necessary to produce healing effects in a shampoo preparation is unknown. Side effects include the production of an eczematous, papular dermatitis in humans.26 Side effects from topical aloe vera use in animals have not been documented.
RESIDUAL-EXTENDING INGREDIENTS Novosomes® Novosomes® (Evasco Pharmaceuticals, Buena, NJ) are extremely stable, specially formulated nonphospholipid microvesicles (i.e., a type of liposome) with five to seven bilayers and a central holding area, 80% of which is comprised of water and/or lipids.27 Novosomes® (approximately 5 µm in diameter) are not susceptible to degradation by hydrolytic enzymes and are stable at temperatures as high as 80˚C. They have increased resistance to the autooxidative process when compared with regular liposomes.27 The particle charge on Novosomes® is formulated to tightly adhere to the skin and hair. The inner solution within the cargo area is slowly released as the various layers break down (requiring 7 to 10 days in average temperature conditions).27 Spherulites® Spherulites® (Allerderm/Virbac, Fort Worth, TX) are composed of multiple layers (10 to 1000) of plant-derived surfactants and are 1 µm in diameter. Spherulites® contain chitosanide—a multipurpose glycoprotein derived from chitin (crustacean shells)—which helps to form a film coating over the skin and hair, as well as an additional shampoo ingredient. Chitosanide also tightly binds the Spherulites® to the hair and skin by providing chemical differences in positive and negative charges. The shampoo ingredient within the Spherulites® is slowly released (over 8 days) as the different layers of the Spherulite® break down. Moisturizing agents, essential oils, and water- and fat-soluble vitamins can all be encapsulated in the same Spherulite®.28 CASE EXAMPLES Case 1 Signalment and History A 2-year-old, spayed female Chihuahua was presented to the Texas Veterinary Medical Center with generalized scaling and a 1-year history of nonseasonal moderate
SALICYLIC ACID s MAGNESIUM LACTATE s MICROVESICLES s CHITOSANIDE
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Diagnosis and Treatment The diagnosis for this dog Physical Examination was atopy and seborrhea sicPhysical examination reca with a secondary bacterial vealed multifocal areas of skin and ear infection. The alopecia on the dog’s face, topical treatment used in shoulders, legs, neck, and Figure 1—Alopecia, lichenification, and mild erythema on this case was a shampoo ventrum (Figure 1). The skin the ventral cervical area of a dog. containing a chlorhexidine was erythematous, licheniand sulfur/salicylic acid fied, and dry with moderate combination with a residuamounts of scale. Both ears al-extending agent (Novowere slightly erythematous somes®). The antibacterial properwith a mild ceruminous disties of chlorhexidine were charge. beneficial for treating the Differential Diagnoses pyoderma, the sulfur/salicylic The main differential diacid combination aided in agnoses for this case were removing scale, and the food hypersensitivity, allerNovosomes ® extended the rehydrating properties of the gic dermatitis secondary to bath. Other appropriate atopy, and allergic contact choices for this case includdermatitis. Other differential diagnoses included bac- Figure 2—Intradermal skin test reactions on the lateral thorax ed using a sulfur/salicylic acid and triclosan shampoo, terial skin infection, fungal of a dog. an ethyl lactate shampoo skin infection, demodicosis, Malassezia dermatitis, and with a residual-extending seborrhea sicca (primary or secondary). The degree of agent (Spherulites®), or a benzoyl peroxide shampoo with Novosomes®. A leave-on conditioner containing pruritus and distribution of lesions helped to eliminate oatmeal and pramoxine was prescribed as a topical scabies from the differential diagnosis list. Because pruagent to help relieve the pruritus; any of the topical ritus was not exacerbated on food rechallenge, a diagoatmeal conditioners or sprays would have been appronosis of food allergy was less likely. The distribution of priate to use in this case. Other medications used in lesions and the history were not consistent with a diagthis case included gentamicin sulfate otic (three drops nosis of contact allergy. Atopy was therefore the most in both ears every 12 hours for 14 days), lincomycin probable underlying cause for this case. The other dif(22 mg/kg every 12 hours for 21 days), hyposensitizaferential diagnoses were ruled out with diagnostic tests. tion vaccines, and hydroxyzine (2.2 mg/kg every 8 Diagnostic Tests hours for 14 days). Several diagnostic tests were performed to reach the Case 2 diagnosis. Multiple skin scrapings were negative for ecSignalment and History toparasites. Impression smears of the skin revealed nuA 10-year-old, intact, male English springer spaniel merous surface cocci around and within keratinocytes was presented at the Texas Veterinary Medical Center (more than 40 per high-power field). Ear-swab cytology with a 6-year history of oily, scaling, thickened skin revealed inflammatory cells (neutrophils) and cocci with alopecia on the dorsum of all four feet, backs of bacteria. Chlorphenolac preparations and dermatoFOOD-ELIMINATION DIET s SKIN SCRAPINGS s CYTOLOGY s ATOPY
pruritus that was sometimes present without dermatologic lesions. The patient was put on a food-elimination diet for 3 months using a commercially prepared venison and potato diet. No increase in pruritus was noted when the original diet was reinstituted.
phyte test media cultures were negative for dermatophytes. An intradermal skin test had numerous positive reactions (grasses, weeds, trees, molds, and house dust mites; Figure 2).
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the ears, caudal thighs, and lateral thorax. This dermatologic condition was mildly pruritic and nonseasonal. Previous treatment included oral and injectable steroids, various antibiotics, and ketoconazole (unknown dose and frequency). According to the owner, steroids, cephalexin, and ketoconazole had somewhat improved the dog’s condition in the past. The dog was fed a commercially prepared Figure 3—Alopecia, lichenification, erythema, crust, and scale along the back of the left pinna of a dog. lamb and rice diet.
biopsy showed evidence of superficial pyoderma with an underlying allergy. The complete blood count showed evidence of eosinophilia, which was thought to be associated with an internal or external parasite load; however, a fecal examination and occult heartworm test were negative for parasites. The urinalysis had abnormal amounts of bacteria, and neutrophils revealed cystitis.
Diagnosis and Treatment The diagnosis for this dog was seborrhea oleosa, allergic dermatitis, and otitis externa with a secondary bacterial skin infection. Topical therapy consisted of twice-weekly baths with a benzoyl peroxide shampoo followed by a leave-on chlorhexidine cream rinse for the superficial pyoderma. Benzoyl peroxide was chosen in this case because Figure 4—Alopecia, lichenification, erythema, and excoriation on the dog had oily skin with a the left lateral stifle of a dog. secondary infection. (A 2% Differential Diagnoses tar shampoo would be an Several differential diagnoses were considered, inappropriate alternative therapy because it is also a cluding allergic dermatitis (e.g., food allergy, atopy, good degreasing agent.) A chlorhexidine leave-on concontact allergy, flea hypersensitivity), ectoparasites (e.g., ditioner was selected because it rehydrates the skin scabies, demodicosis), and a secondary skin infection and provides some secondary residual antibacterial ef(e.g., bacterial, fungal). Although the ears and stifle arfects. Any moisturizing agent would be appropriate eas were involved, the possibility of scabies was low beand was considered necessary because benzoyl peroxcause pruritus was mild and the condition was present ide tends to be drying. The otitis externa was treated for a relatively short time (6 years). with gentamicin sulfate otic (three drops every 12 hours for 14 days). A commercially prepared duck Diagnostic Tests and potato diet was prescribed for an 8-week eliminaMultiple skin scrapings were negative for ectoparation diet. sites. Impression smears of the skin and crust revealed The dog was markedly improved at the end of the 8numerous cocci and some neutrophils and macroweek food trial (pruritus decreased more than 50%). At phages (more than 30 per high-power field). Numerous the conclusion of the trial, rechallenge with the dog’s cocci bacteria and neutrophils were noted on the earold food confirmed food allergy (pruritus increased swab cytology. Otoscopic examination of both ears remore than 50% within several days of food rechalvealed patent ears with intact tympanic membranes. lenge). Challenging the dog with individual food ingreChlorphenolac preparation and dermatophyte test medients revealed allergies to beef, egg, wheat, soy, and dia cultures were negative for dermatophytes. Skin chicken. Physical Examination Physical examination revealed several dermatologic abnormalities, including alopecia, erythema, lichenification, excess scale, and some crusts on the face, caudal aspect of both pinnae (Figure 3), ventral neck and ventrum, and extremities (especially the stifles and dorsum of the feet; Figure 4). The canals of both ears were erythematous with a ceruminous discharge.
CHLORPHENOLAC PREPARATION s EOSINOPHILIA s FOOD ALLERGY
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DISCUSSION Both of the patients discussed in the case examples had bacterial pyoderma and allergy, but they were treated with different topical therapies because their skin and hair had different tactile properties. The dog in the first case had dry scale that required a moisturizing keratolytic and keratoplastic agent, whereas the second dog had oily scale requiring a degreasing and keratolytic agent. The main complaint of the first dog’s owner was pruritus, thus a leave-on oatmeal with pramoxine conditioner was selected. The history of pruritus without any evidence of dermatologic lesions suggested that allergy was a reasonable differential diagnosis. The haircoat and skin of the second dog were oily and the dog was mildly pruritic, thus a degreasing shampoo (benzoyl peroxide) and leave-on chlorhexidine conditioner were considered appropriate therapy. Systemic antibiotics were used in addition to the topical therapy to treat the skin infection. Recheck visits help determine whether antibiotics have been administered for an appropriate length of time (minimum of 3 weeks). As in the first case, the dog in case 2 was still pruritic even though the pyoderma was cleared. This clinical information along with the biopsy results indicated that food allergy was a reasonable differential diagnostic concern. These cases demonstrate that tactile and visual findings, cytology results, and the owners’ primary concerns should be considered when selecting topical therapy to maximize a patient’s chance of benefiting from it. As was done in these cases, owners should also be informed that their pets’ skin condition could change with time and thus a shampoo or conditioner that was once appropriate may not be in the future. Finally, these cases demonstrate that more than one topical therapy may be appropriate for a particular patient. About the Author
Dr. Rees is affiliated with the Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M University, College Station, Texas. She is a Diplomate of the American College of Veterinary Dermatology.
REFERENCES
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4. Ascher F, Maynard L, Laurent J, Goubet B: Controlled trial of ethyl lactate and benzoyl peroxide shampoos in the management of canine surface pyoderma and superficial pyoderma, in von Tscharner C, Halliwell REW (eds): Advances in Veterinary Dermatology, ed 1. London, Bailliere Tindall, 1990, pp 375–382. 5. Scott DW, Miller WH, Griffin CE: Dermatologic therapy, in Muller and Kink’s Small Animal Dermatology, ed 5. Philadelphia, WB Saunders Co, 1995, pp 174–277. 6. Sebben JE: Surgical antiseptics. J Am Acad Dermatol 9(5): 759–765, 1993. 7. Sanchez IR, Nusbaum KE, Swaim SF, et al: Chlorhexidine diacetate and povidone–iodine cytotoxicity to canine embryonic fibroblasts and Staphylococcus aureus. Vet Surg 17(4): 182–185, 1988. 8. Lozier SM: Topical wound therapy, in Harari J (ed): Surgical Complications and Wound Healing in the Small Animal Practice. Philadelphia, WB Saunders Co, 1993, pp 63–88. 9. Zamora JL: Povidone–iodine and wound infection. Surgery 95:121–122, 1984. 10. Zamora JL: Chemical and microbiologic characteristics and toxicity of povodone–iodine solutions. Am J Surg 151: 400–406, 1984. 11. Swaim SF, Lee AH: Topical wound medications: A review. JAVMA 190(10):1588–1593, 1987. 12. Osuna DJ, DeYoung DJ, Walker RL, et al: Comparison of three skin preparation techniques in the dog. Part 2. Clinical trial in 100 dogs. Vet Surg 19(1)20–23, 1990. 13. Zuckerraun HL, Babich H, May R, Sinensky MC: Triclosan: Cytotoxicity, mode of action, and induction of apoptosis in human gingival cells in vitro. Part 1. Eur J Oral Sci 106:628–636, 1998. 14. Kwochka KW: Rational shampoo therapy in veterinary dermatology. Proc 11th Annu Kal Kan Symp Treat Small Anim Dis:87, 1998. 15. Jawetz E: Antifungal agents, in Katzung BG (ed): Basic and Clinical Pharmacology. Los Altos, CA, Appleton and Lange, 1987, pp 554–558. 16. Leyden JJ, McGinley KJ, Mills OH, et al: Effects of sulfur and salicylic acid in a shampoo base in the treatment of dandruff: A double-blind study using counts and clinical grading. Cutis 39:557,1987. 17. Rosenkrantz WS, Griffin CE, Walder E, et al: Superficial suppurative necrolytic dermatitis in miniature schnauzers: A retrospective analysis. Proc ACVD/AAVD: 99, 1991. 18. Basset NG (ed): Herbal Drugs and Phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994, pp 96–98. 19. Klein AD, Penneys NS: Aloe vera. J Am Acad Dermatol 18:714–720, 1988. 20. Haliwell REW: The use of shampoos in veterinary practice. Vet Annu 36:127–141, 1996. 21. Saeed SA, Butt NM, McDonald-Gibson WJ, et al: Inhibitor(s) of prostaglandin biosynthesis in extracts of oat (Avena sativa) seeds. Biochem Soc Trans 9(5): 444, 1981. 22. Riboldi A, Pigatto PO, Altomare GF, et al: Contact allergic dermatitis from oatmeal. Contact Dermatitis 18(5): 316– 317, 1988. 23. Pigatto P, Bigardi A, Caputo R, et al: An evaluation of allergic contact dermatitis potential of colloidal grain suspen-
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sions. Am J Contact Dermatol 8(4):207–209, 1997. 24. Moore PK, Hoult GR: Selective actions of aspirin and sulfasalazine-like compounds against prostaglandin synthesis and breakdown. Biochem Pharmacol 31:969–971, 1982. 25. Lehninger A (ed): Biochemistry, ed 2. New York, Worth, 1981, p 578.
26. Morrow DM, Rapaport MS, Strick RA: Hypersensitivity to aloe. Arch Dermatol 116:1064–1065, 1980. 27. Corll D: Novosomes® vs. liposomes. Evasco Pharmaceutic Newslet 1:1–2, 1998. 28. Koch HJ: Spherulites® Technical File. Fort Worth, TX, Allerderm/Virbac, 1998, pp 1–33.
