April 2005

Canine and Feline Dermatology and Otology

Rod A. W. Rosychuk, DVM, DACVIMColorado State University

Diagnostic Techniques in Dermatology: An Update

Dermatology can be frustrating! Part of the dilemma is the fact that many skin diseases look alike. As a result, we routinely perform certain diagnostics on each case. Although we are all quite familiar with many of these tests, it may be of value to not only review some of the "basics", with emphasis on maximizing their benefit, but also to provide a few new "twists" that will be additions to your diagnostic armamentarium.

Tips for the evaluation of ectoparasites: 1. Scabies: Ideally clip prior to scraping. Perform multiple, broad scrapes

emphasizing areas where mites are most likely to be found: margins of pinna, outer aspect of pinna, lateral stifles, lateral elbows, ventrum.

2. Cheyletiella: We usually do a combination of scrapes and combings for this mite. We often scrape scaly areas over the back before clipping, getting as much debris on our slide as possible. Scrapings are then done on a clipped area as well. A flea comb can be used to comb the coat, getting as much scale and debris as possible. This may be placed in a petri dish and examined under a hand lens or lowest power on your microscope. We prefer the combings to acetate tape preparations, mostly because they provide us with more debris. If acetate tape is used, as much debris as possible is collected on the tape by "tape stripping" the skin. The tape is then laid on a slide and examined under the microscope.

3. Demodex: a. Hair plucks. We often will pluck difficult to get to places such as

peri-ocular regions or inter-digital spaces in bouncy or aggressive dogs. Several hairs are plucked from affected areas and placed on a slide with a couple of drops of mineral oil. A cover slip is placed over this. It may help to move the cover slip around with a little bit of pressure, to help move the mites away from the base of the hair shafts. This technique may miss mites in the dog . If the procedure is negative, scrapings should be performed to rule out a diagnosis of demodex. Both scrapings and plucking are always done on cats suspected of demodicosis. Cats may not only have the follicular demodex mites commonly seen in dogs, but may have a short, stubby mite that lives on the surface of the epidermis and not deeper in the hair follicle (demodex gatoi). Note: if hair plucks are negative for demodex, then the sample should be examined for dermatophyte arthrospores or hyphae (see below).

b. Scrapings. We will always clip prior to scraping; squeeze the skin prior to scraping. Emphasis is on deep scrapings from several representative areas.

c. When patients have generalized demodex and concurrent otitis externa, they usually have mites in their ears as well. These can usually be seen by just swabbing the ears, placing the debris on a slide, putting a drop of oil and a cover skip over this and examining it under the 10 X lens.

d. What do you see? In the dog: demodex canis, demodex injai (long bodied mite; patch of oily seborrhea over back), short bodied mites; cats: demodex felis, demodex gatoi (short, stubby mite)

Diagnostics for Malassezia:

The importance of Malassezia in the pathogenesis of several skin disorders in the dog is now well known (e.g. atopy, food sensitivity, seborrheic disorders). More recently, it has also been noted as a complicating factor in various feline dermatoses (e.g. atopy, food sensitivity). There are many techniques used to document the presence of Malassezia. In our clinic, scrapings, impression smears, swabs and tape impressions are all used with equal frequency but in different scenarios.

Superficial scrapings are used on inflamed areas that may have a fair amount of oily/waxy debris (inter-digital spaces, inguinal regions, anterior elbows). Material is squashed on the slide (bread and butter -like application) heat fixed for 2-3 seconds, then stained with Diff Quick. Dry cotton swabs work well in areas that are more difficult to get to (crevices in inter-digital spaces, perivulvar folds, lip folds). The swab is rubbed in the affected area, then rolled on the slide. Impression smears with a slide are best used in an area that is quite oily/waxy and reasonably flat (e.g. inter-digital spaces of larger feet; inguinal area, peri-anal area). The slide should be firmly pressed against the skin; several imprints of the same area are often recommended. Acetate tape preparations are best used when the area is drier (not waxy). It is also a quick, well tolerated procedure that can be done on difficult to restrain individuals. A section of tape just a little shorter than the length of the clear portion of the slide is used. The tape is pressed firmly and repeatedly on the surface of the area examined (e.g. inter-digital spaces, inguinal regions); a drop of Diff Quick is then placed on the slide and the tape is laid over this. The stain is then distributed over the length of the tape by placing pressure on the tape; excess stain is removed by compressing a blotter (e.g. absorbent paper towel) over the slide. Tape preparations do appear to be more difficult to read. This is especially true when evaluating for the presence of bactreria in that they may be difficult to differentiate from debris. In the author's experience, this technique also does not yield as many organisms as other techniques might (with the exception of dryer areas wherein it appears to have an advantage over other techniques). Interpretation of numbers of Malassezia is controversial. In that individuals may develop a hypersensitivity to Malassezia, relatively small numbers may be problematic. Therefore, if 1 or 2 Malssezia per oil immersion field are seen, and the clinical signs suggest that Malassezia may be contributory (inflammation in a an area predisposed to Malassezia; lichenification), then trial treatment for Malssezia should be performed.

Diagnostics for Dermatophytes Wood's Lamp Examination: The Wood's lamp should be turned on for 5 - 10 minutes prior to use. Positive fluorescence is yellow-green in color. The hairs themselves should fluoresce. In that some waxy debris adherent to hairs may give the appearance of fluorescence, hairs may be plucked to see if the proximal part of the hair fluoresces. If the hair is infected with a dermatophyte, the proximal portion and root of the hair will fluoresce. If waxy debris is the source of

suggestive fluorescence, its fluorescence will not extend lower than the skin surface. Suspected fluorescent hairs are also the best hairs to use when examining for the presence of arthrospores. Recall that only 30 - 40% of M. canis samples will fluoresce. Other dermatophytes will not fluoresce. A positive fluorescence is highly suggestive of dermatophytosis, but negative results do not rule it out.

Potassium Hydroxide / Mineral Oil Preparations: Although potassium hydroxide has classically been used to "clear" hair samples to facilitate the identification of arthrospores, we usually do this examination in mineral oil, without KOH. Hair samples are placed in a couple of drops of mineral oil and covered with a cover slip. Under the 10X or 40X lens we look for hairs that have abnormal contours (rotten log appearance) compared to normal hairs. Arthrospores or hyphae are usually seen with the 40X lens, but oil immersion may be necessary. Tip: practice your observational skills on dermatophyte infected hairs that fluoresce with the Woods lamp. These hairs usually have arthropsores that are more predictably observable. If a 20% KOH clearing solution is used, a few drops of KOH are applied to hairs on the slide and this is covered with a cover skip. The slide is read in about 5-20 minutes. Warming the slide will hasten the clearing and time to reading.

Fungal Culture: Although there is not much new information regarding culturing for dermatophytes, a few points bear re-visiting. There are now several culture media available. Some have color indicators. These include DTM (Dermatophyte Test Medium; dermatophyte growth produces red color change), Rapid Sporulating Medium (dermatophyte growth produces blue-green color change). Recall that dermatophytes should produce media color change within 24 hours after colony growth. They do this by metabolizing proteins in the media to alkaline by-products which mediate the color change. Saprophytes may also change the media color, but it takes several days after colony growth is noted. Saprophytes metabolize the carbohydrates in the media first, but after they exhaust this, they will then metabolize proteins to produce alkaline by products. We generally circle and date the area immediately over colony growth when it is first noted, to facilitate the interpretation of changes. Colony growth is usually noted within 10 days, although we monitor the media for 3 weeks. There have been some reports of dermatophytes that have not changed the media color. Ideally, all suspect dermatophyte colonies should be speciated to confirm their identification. Noting the type of dermatophyte may offer some epidemiologic insight into the source of the infection. Any colony that grows out white or buff colored should be speciated. Hyphae should be teased away from the colony and placed on a glass slide with a drop of lactophenol cotton blue. The preparation is examined for the characteristic macroconidia of the dermatophyte. Veterinary reference sources such as Scott's Small Animal Dermatology textbook can be used to help in the identification. Colonies have to be quite mature (i.e. 7-10days) before producing macronidia. If these structures are not seen initially, the speciation attempt should be repeated every 2-3 days. Although RSM (rapid sporulating media) has been marketed to enhance sporulation, this has not been proven in one study. Other media available for diagnostic purposes do not have a color indicator included. An example is Mycotec (sabouraud's dextrose). It provides for the development of the classical pigmented colony color and morphology of fungal species. It also provides for more rapid sporulation and the development of macroconidia. In our laboratory, we use Derm-Duets from Bacti-lab, PO Box 1179, Mountain View, California 04042, 1-8000-227-7300 (DTM and RSM - rapid sporulating media) or Sab-Duet (DTM and Mycotec agar). Especially in suspected asymptomatic carrier cats or cats who are on therapy and being re-cultured, sample collection can be facilitated by toothbrush collection. The toothbrush is combed through the coat, gathering up as much hair and debris as possible. The toothbrush is then impressed on the culture media surface or, alternatively, hair and debris is removed from the tines on to the culture media.

Cytologic Examination Cytologic examination should be considered in any case wherein one is trying to establish a cause for pustules, erosions, ulcers, draining tracts, plaques, papules, nodules or tumors. Collection techniques include fine needle aspirates, surface impression smears, impression smears of cut surfaces or lanced pustules or papules. Tip: cytologic sample collection for impression smears can often be facilitated by "squeezing" the skin to facilitate exudation. Samples may be distributed over the slide by doing non-traumatic "squash" preparations or brush cytology. In brush cytology, the sample is placed on a clean glass slide and then spread out using a camel hair brush. The brush is then rinsed well and dried for future use. This technique gives single cell layer distribution on the slide, with a minimum of trauma to the sample. Staining is usually done with modified-Wrights stain (Diff-Quck Stain). These slides can be catalogued and used for future reference/teaching etc. Supra-vital stains such as New Methylene Blue are also easy and rapid.

Cytologic examination of debris taken from ears should be performed in each examination and re-examination of patients with otitis externa. Material is usually collected by placing a swab down in to the ear as far as it goes comfortably (usually the junction of the horizontal and vertical canal). Debris is then rolled out on a slide and the slide is heat fixed (match or lighter under slide for 2-3 seconds). The slide is then stained with Diff-Quick and examined under 10X, 40X and then oil immersion. Samples are examined primarily for bacteria, Malassezia and neutrophils. A record of relative numbers should be established (e.g. use a scale of 1+ - 4+ with 1+ being a little more than normal, 4+ being full fields of organisms). The observation of an occasional bacterium or Malassezia per oil immersion field would be considered normal.

Cytologic examination of debris taken from anal sacs is primarily done to document the presence of anal sacculitis. Debris expressed from the anal sac is placed on a slide and then "squash" prepped and stained with Diff-Quick. The sample is examined under oil immersion. Normal anal sacs should contain pleomorphic bacteria, epithelial debris, and some amorphous, bluish material that often appears about white blood cell size, but has indistinct borders and no nucleus. Patients with anal sacculitis will have large numbers of neutrophils or neutrophils and eosinophils. In some samples, eosinophils may predominate.

Trichography

Hairs are pulled with the fingers or very carefully with forceps (to minimize trauma to the hairs), placed in mineral oil on a slide and examined under low power. Broken hairs suggest self inflicted alopecia or dermatophytosis, large melanin clumps in hairs may suggest color dilution alopecia, large numbers telogenized hairs (club or spear-shaped) versus anagen hairs (bulbs are rounded, smooth, root is often bent because it is soft) may suggest telogen defluxion or an endocrine disturbance. Hairs that are inappropriately curled, misshapen and malformed suggest nutritional or metabolic disease.

Bacterial Culture and Susceptibility Testing: Bacterial C+S testing should be considered in any skin lesion (pustules, abscess, cellulitis, deep or superficial pyoderma or acral lick dermatitis) for which bacteria are considered a differential diagnosis but response to appropriate antibiotic therapy is lacking or any of those suspect bacterial problems which are severe and warrant an accurate antibiotic choice for initial therapy (e.g. severe deep pyoderma in a patient with severe, generalized demodicosis).

Ideally, samples should be collected from unbroken pustules, by needle aspirates, or by biopsy (submitting sections of skin for culture). Every attempt should be

made to minimize surface contamination of samples. Unbroken pustules are not prepped to prevent false negative cultures. Samples to be taken by biopsy are not cleaned prior to biopsy. Once the sample has been harvested (e.g. 4 mm punch biopsy), the very superficial surface of the sample can be trimmed away with a sharp scalpel blade (to minimize surface contamination). Deep, draining tracts may also be cultured by surgically preparing the surface of the lesion, drying this surface well, then squeezing the tissues and culturing exudates from deeper within the tissue. It has been recently shown that epidermal collarettes (manifestation of superficial bacterial pyoderma) can be cultured by rolling a dry swab over the collarette area 3-4 times (to be considered as an alternative to culturing from unbroken pustules or taking samples by skin biopsy).

Skin Biopsies 1. Indications

a. Atypical or uncommon appearing skin lesions b. Suspect neoplastic diseases c. Lesions which have been poorly responsive to rational therapy d. Lesions suggestive of autoimmune or immune mediated disease e. Severe or chronic ulcerative or erosive skin disease

2. When to biopsy? a. Early in the course of the disease; before trauma, trial therapies or

chronicity alter helpful morphologic changes. 3. What to biopsy?

a. Samples from all representative, morphologically distinct lesions b. Entire bullae or pustules - intact if possible c. For inflammatory lesions

i. Junctional (transition between normal and lesional skin) ii. Lesional area iii. If crusts are present, should always biopsy through the crust

and include the crust with the samples submitted. iv. For alopecic disorders: most alopecic area; transitional zone

and more normal area. Multiple biopsies, especially from alopecic area.

v. Care should be taken to avoid biopsying full thickness ulcers (lack of epidermis usually compromises interpretation).

4. How to biopsy? a. Carefully clip; no surgical cleansing/scrubbing allowed for samples

to be examined histologically unless the lesion is beneath the skin (covered by normal epithelium). Do not disturb scales, crusts etc. (they must be part of the biopsy specimen).

b. Mark biopsy site with indelible pen (i.e. Sharpie) (circle, dots) to allow for documentation of where local anesthetic has been placed.

c. Can get by with local anesthesia and manual restraint or light sedation for most biopsies in the dog and horse; cat often requires heavier sedation.

d. Make bleb in subcutis under lesion with 2% lidocaine +/- 2% epinephrine. Enough epinephrine can be supplied by rinsing the barrel of the syringe with epinephrine before filling with lidocaine. Usually 1/2 to 1 cc enough at each site (beware: multiple blebs in small dogs - potential for lidocaine toxicity; can dilute lidocaine to 1% to circumvent this). Wait 2-5 minutes prior to biopsy.

e. Cats generally biopsied under ketamine restraint (1-2 mg/lb IV) without local. However, small amounts of lidocaine (dilute to 1%) not contraindicated. Use 1/4 to 1/2 cc per site.

f. Horses: sedation (e.g. xylazine) plus local, subcutaneous block as noted above is usually adequate.

g. If disease of the subcutaneous fat suspected, a regional or ring block or general anesthesia is recommended. The administration of SubQ lidocaine is not acceptable (will distort tissues).

h. Use scalpel blade or biopsy punch to excise lesion totally, if possible.

i. If using a punch biopsy to take a sample from across the junction of a lesion, draw a single line perpendicular to the junction with a fine tipped "Sharpie" pen. The line should then bisect the punch sample taken. Make sure you tell the pathologist to cut the sample in along this line. This will guarantee that your sample will be cut in across the junction of the lesion.

j. For alopecic disorders (hairloss) - draw a line parallel to the "lie" of the hair. Center the biopsy punch on this line and have the sample cut in on the line. This allows for a more complete view of hair follicles and associated structures when the samples are examined histologically.

k. If junctional biopsy, you can also use a scalpel blade to take an elliptical wedge, making sure you have a significant amount of tissue on either side of the lesion border. This allows for proper orientation when the sample is "cut in" by the pathology laboratory (i.e. the pathologist will always cut these samples in from tip to tip of the ellipse, thereby assuring that your sample will be cut across the junctional line.

l. Cutaneous biopsy punches : disposable 8 or 6 mm punches recommended. 4 mm punches occasionally used for biopsies in difficult areas (e.g. facial region, feet).

m. Use fine eye forceps to grasp edge of biopsy (ideally edge of deep dermis or superficial subcutaneous tissue; pull up) and iris scissors directed deep in to cut space to cut subcuticular tissue. Recall, these are small samples… emphasis must be placed on minimizing crush artifact!!!

n. Ellipse biopsies: place on a small piece of wood, cardboard or blotting paper, SubQ side down (this side will stick to wood etc.) to prevent "rolling up". Then turn wood/cardboard upside down and place in formalin.

o. Place in 10% neutral phosphate buffered formalin as soon as possible

p. Suture biopsy site. Simple interrupted or cruciate suture acceptable.

q. Emphasis should be placed upon taking multiple samples (at least 3 or 4). If possible, should identify biopsies as to where each came from (e.g. place in separate labeled vials or mark with Indian ink or very fine, ophthalmalogic suture).

r. Submit samples with a complete, relevant history to a veterinary dermatohistopathologist or pathologist with an interest and expertise in dermatopathology. Folks with this type of training will be more likely to give you good differential diagnoses for histologic findings.

CANINE ATOPY: AN UPDATE

Atopy is defined as the heritable predisposition to the production of IgE (reaginic antibody) to otherwise ordinary environmental substances such as pollens, molds and house dust mites. It has been hypothesized that atopic individuals tend to produce a T helper 2 cell response to allegens. The Th2 cells produce cytokines which stimulate B cells to produce IgE. In contrast, nonatopic individuals tend to have a Th1 response to environmental allergens. These cells produce cytokines that suppress the proliferation and function of the allergy-promoting Th2 cells, thereby inhibiting IgE production. Allergen exposure is thought to occur both through the respiratory tract and through transcutaneous absorption of allergens.

With transcutaneous absorption, epidermal Langerhans cells trap and present allergen to T- lymphocytes which subsequently migrate to regional lymph nodes to culminate in the production of allergen specific IgE (and possibily IgGd) from B lymphocytes. IgE then binds to cutaneous mast cells. Subsequent exposure to allergen (e.g. cutaneous exposure) results in binding of this antigen to IgE, mast cell degranulation and the release of mediators of pruritus and inflammation (e.g. proteolytic enzymes, leukotrienes, prostaglandins, serotonin etc.). The influx of inflammatory cells results in the release of cytokines which may perpetuate inflammation for hours or days after allergen exposure. In human atopy, it is now thought that the disease may also eventually involve an autoimmune component wherein, due to molecular mimicry, IgE is sensitized to self proteins.

Incidence: Atopy is thought to affect as many as 15% of the canine population in the U.S. . There is strong breed predilection (e.g. Golden retriever, Labrador retriever, Cocker spaniel, Shar pei, Dalmation, Boxer, Terriers (WHW, Yorkshire, Cairn, Scottish, Wirehaired, Boston), Pug, Irish Setter, Chihuahua, English Bulldog, Lhasa Apso, Miniature Schnauzer, German Shepherd). Although heritability has been strongly suspected for years, it has only recently been confirmed in Labrador and Golden Retrievers (Shaw S et al, AJVR 2004), prompting the recommendation that affected individuals not be used for breeding purposes.

Allergic to What?

Pollens of weeds, trees, grasses, house dust mites, molds, feathers, animal danders (cat, horse, cow), insects, storage mites (Tyrophagus putrescentiae, Leipidogyphus destructor, Acarus siro), human dander?

History and Clinical Signs: 1. Atopic symptoms generally develop between 6 months and 6-7 years of

age with the peak onset between 1-3 years. We do see individuals affected as young as 2-3 months of age.

2. Although the majority of atopics initially have seasonal pruritus, their problems worsen with age and 75 - 85% of cases will become nonseasonal.

3. The primary feature of atopy is pruritus with the vast majority of other signs created as the result of this pruritus (i.e. secondary salivary staining, erythema, hyperpigmentation, lichenification, self induced alopecia). However it is now noted that there can be some degree of a primary eruption associated with atopy (erythema or a papular dermatitis) - these changes without pruritus.

4. Pruritus and lesions generally involve the periocular region, ears, feet, flanks, axilla, anterior elbow, dorsal back, perivulvar and perianal regions. Not all areas need be affected in the same dog. Pruritus and lesions are usually quite symmetrical.

5. 80% - 85% will have otitis externa. The proximal pinna (entrance to vertical canal) tends to be most characteristically involved. Secondary malassezia/bacterial infections common. In our area, underlying atopy is the most common cause of recurrent aural hematomas.

6. Secondary seborrheas (sicca or oleosa) are common. 7. Superficial (at at times, deep) bacterial infections primarily caused by

Staphylococcus intermedius- common. Atopy in the dog has been noted to predispose to recurrent staphylococcal infections through a number of mechanisms:

a. The skin of atopic dogs has been shown to allow for greater adherence of Staph. to the skin surface (promoting increased colonization and likely predisposing to infection).

b. Atopic dogs have been noted to have abnormal immunologic responses which may predispose to infection

c. Secondary seborrhea and self trauma may also provide

microenvironments that predispose to secondary infections

Staphylococcal colonization and infection may or may not be pruritogenic in an atopic individual. They may significantly contribute to the production of pruritus through the production of pruritogenic proteases and the production of staphylococcal IgE (Staphylococcal hypersensitivity). In man, it is also noted that Staph. may produce endotoxins that serve as superantigens which may actually perpetuate the allergic response. It has also been noted that these superantigens may actually interfere with the anti-inflammatory action of glucocorticoids in the skin.

Staphylococcal infections may be very important to the clinical signs manifest in a given allergic individual (so much so, that just by controlling infections, the overall comfort of the individual will be improved very significantly). Control of the underlying allergic disease often results in a reduced tendency to develop infections in these individuals. However, there is a smaller subset of individuals who will remain prone to recurrent infections, even with control of the underlying allergy.

8. Malassezia colonization / infection - common. Some affected individuals have been noted to develop IgE mediated Type I hypersensitivity to intracellular protein extracts of Malassezia pachydermatis. These reactions may as well contribute significantly to the development of pruritus and inflammation. They also raise questions about the significance of Malassezia based on assessment of numbers of organisms. Where hypersensitivity reactions are involved, smaller numbers of yeast may contribute significantly to symptomatology. The above observations argue for the diligent management of secondary Malassezia infections to maximize comfort for our patients.

9. Hyperhidrosis (usually with more severe, chronic disease; severe inflammation of skin) - less common

10. Lick granuloma and acute moist dermatitis ("hot spots") - uncommon 11. Conjunctivitis, rhinitis, reverse sneezing, asthma-like symptoms -

uncommon 12. Anal sacculitis - uncommon 13. Lethargy, irritability, weight loss (with severe disease) 14. It is common to see concurrent flea bite hypersensitivity in atopic dogs. 15. 5 - 10% of atopics will have concurrent adverse reactions to food

Diagnosis -The diagnosis of atopy is accomplished largely by history, physical examination and rule out (i.e. differentiating atopy from other pruritic diseases such as flea bite hypersensitivity, scabies and food allergies). The histology of canine atopy is relatively non-specific, exhibiting an inflammatory pattern characterized as chronic, hyperplastic (thickened epidermis) and spongiotic (epidermal edema) with perivascular accumulations of lymphocytes mast cells (35% of cases?) and low numbers of eosinophils.

Intradermal testing or serologic testing for atopy are primarily performed to formulate solutions for hyposensitization. They may also provide data to allow for avoidance from some allergens. Due to the potential for both false positives and negatives, these diagnostics should only be performed in patients who are highly suspect to be atopic.

Intradermal testing appears to provide more specific data than serologic testing (less false positives). With-drawl times for various medications prior to testing include two weeks for antihistamines, 4-6 weeks for oral glucocorticoids, 8 weeks for "depo" steroids (keeping in mind that with longer term, higher dosage therapy, with- drawl times may be much longer than these) and two to three weeks from relatively short term topical glucocorticoids. Although the author also

recommends a two week with-drawl from fatty acid therapy, this point is controversial. It is important to note that "false" negative tests may occur in as many as 20 - 30% of cases. These negatives may be a product of previous medications, off season testing (testing more than two months after the end of the season) and inherent host factors (estrus, pseudopregnancy, stress). In atopics with severe clinical signs it has been suggested that anergy occurs with excessive mast cell degranulation, and that no additional degranulation can be triggered with the skin test injections, giving a false negative result. In man, it is also noted that as many as 20% of atopics will be negative on both skin tests and in vitro serologic testing. These individuals have been said to suffer from "intrinsic" atopy (vs extrinsic atopy) wherein their atopy involves an inherent abnormality in their immunologic responses which are devoid of extrinsic factor influences (allergen exposure etc).

In vitro serology is considered less specific than intradermal testing, but is still a reasonable alternative to IDT. Both false positives and/or false negatives may be a trait of any given test. Antihistamines or fatty acids need not be discontinued for this testing. With-drawl times for oral glucocorticoids are controversial and may vary with the test. In general, a two to three week with-drawl time is recommended by the author. The Heska test, however, may require an even much longer with-drawl (weeks to months). It is interesting to note that the success rates of immunotherapy based on the results of IDT compared to those obtained using serologic tests are comparable in several studies (i.e. about 60% success). Some dermatologists are routinely doing both intradermal and serologic testing and utilizing the data from both in establishing hyposensitization protocols. This approach is rationalized on the basis that the two tests measure different things. IDT measures IgE in the skin while serology measures circulating IgE and a direct correlation may not exist between the two.

Management of Recurrent Staphylococcal Infections 1. Do as much as possible to control underlying allergy 2. Treat each "flare" of pyoderma with an appropriate anti-staphylococcal

antibiotic for appropriate duration of time (Clavamox, lincomycin, cephalexin):

a. Superficial, infrequently recurrent, localized - 3 weeks b. Severe, generalized, deep (even if focal) - 1-2 weeks beyond

complete remission 3. Germicidal Shampoo - once weekly (Benzoyl peroxide, chlorhexidine, ethyl

lactate) +/- Germicidal Conditioner (ResiChlor; residula chlorhexidine conditioner; Virbac) or +/- Antipruritic conditioner (e.g. ResiProx; pramoxine and oatmeal; Virbac)

4. Germicidal wipes / sprays a. Chlorhexidine and miconazole (Malaseb spray or pledgets, DVM

pharmaceuticals) - once or twice daily to initiate therapy; once every 2-3 days for maintenance.

b. Acetic acid, boric acid (Malacetic wipes; DermaPet) - used as for Malaseb above

5. Topical antibiotics - for early treatment of recurrent lesions; mupirocin (Bactoderm, Pfizer)

6. Patients who are very prone to recurrent bacterial infections and who derive significant benefit from systemic antibiotic therapy:

a. Pulse cephalexin therapy; once infection has been put in to remission with routine dosages of cephalexin (22 - 32 m/kg BID), pulse with full dosages for 2 or 3 consecutive days of each week, whether there is infection or not)

b. Immunomodulators c. Staphage lysate - .5 cc twice weekly or 1 cc Sub Q once weekly for

at least 4-6 month trial. Use systemic antibiotics initially to get infection under control, then discontinue to assess the benefit of

the Staphage lysate. If a flare of infection noted, again treat in to remission and assess again. If recurrence of infection is not noted for a couple of months after discontinuing, begin to reduce the frequency of administration by weekly increments (looking to get to 1 cc given once monthly). If a flare of infection is noted, can transiently increase frequency of administration again.

i. Interferon Alfa -2A (human recombinant, Intron-A, Schering), feline recombinant (Virbagen Omega, Virbac; available only in Europe and Canada at this time) or canine recombinant (available in Japan) : cytokine that has antiviral, antimicrobial , antiproliferative and imunomodulating effects. Enhancement of anti-microbial effects are thought to occur through IFNs ability to enhance macrophage activity. Low dose, daily, oral therapy (1000 units human interferon; total dose for all sized dogs) is suggested to have some benefit in reducing the incidence of infections in atopic dogs; higher dosages (10,000 U / Kg canine interferon or 1 million unites feline reconmbinant, three times weekly) have been noted to have some beneficial effects in reducing the signs of atopy (through altered cytokine release and decreased IgE production). Efficacy of interferons interchangeable (canine, feline, human?) E.g. Buy 5 million units/.2 mls (1.5 mls total; cost to Vet $135.00; shelf life - 6 mos to 1 year ? ); 0.1 ml in 250 ml saline (1 ml - 10,000 units); freeze in 3 ml aliquots - good for 1 year frozen??? Thaw and dilute 3 ml in 27 ml saline (1,000 U per ml). Keep refrigerated. Give 1 cc (1,000 U) per dog PO once daily. Discard after 1 month and go on to the next frozen vial. 6 month trial.

7. Patients who are very prone to recurrent Malassezia colonization/infection: a. Systemic therapy is often most convenient and effective.

Alternatives include ketoconazole (5-10 mg/kg PO once or twice daily) for 2-4 weeks. The author generally starts at 5 mg/kg BID. Recurrences of disease can be treated with lower dosages (e.g. 5 mg/kg daily) to assess efficacy. Alternative, more expensive therapies include itraconazole (Sporanox ®, Janssen; 5 mg/kg daily for 2-4 weeks) or fluconazole (Diflucan ®, Roerig; 5-10 mg/kg q 24 hrs to once weekly?). Both are less likely to have the dileterious side effects associated with ketoconazole. For patients with recurrent Malasseiza, maintenance can be attempted with ketoconazole (5 mg/kg for 2 or 3 days of each week), itraconazole (5mg/kg, 2 consecutive days of the week) or fluconazole (5-10 mg/kg once weekly?).

b. Topical therapies are less expensive, but also less effective alternatives for treating Malassezia. They are, however, valuable as adjunctive therapies to systemic drugs and as maintenance therapies once infections have been resolved. Anti-fungal, degreasing shampoos include:

c. miconazole/chlorhexidine gluconate - Malaseb ™ (DVM) i. ketoconazole/chlorhexidine- KetoChlor ™ (Virbac) ii. Ketoconazole - Nizoral ™ (Janssen) iii. Acetic acid/boric acid - Malacetic ™ (DermaPet) iv. Chlorhexidine - Chlorhexiderm ™ (DVM); Hexadene ®

(Virbac), Seba-Hex ™ (EVSCO).

These shampoos should be lathered well, left on for 5- 10 min., rinsed well and repeated every 2-3 days for 2-3 weeks, then reduced in frequency of use for maintenance treatment.

d. Rinses that can be applied and left on for residual benefit (i.e after

shampoos) include: e. miconazole - ResiZole ™ (Virbac)

i. chlorhexidine - ResiChlor ™ (Virbac) ii. acetic acid and water 1:1 (white vinegar in equal parts with

water). f. Convenient topicals often added to the "between shampoo"

regimens include germicidal wipes or sprays used once or twice daily:

g. Acetic acid, boric acid - MalaAcetic Wipes ™ (DermaPet) i. Miconazole, chlorhexidine - Malaseb Wipes ™ or spray (DVM

pharmaceuticals)

Avoidance 1. With the realization of the potential importance of transcutaneous

absorption of allergens, emphasis should be placed on frequent bathing (to remove allergen from the surface of the skin) and even more minor techniques such as rinsing the feet (i.e. dog with atopic pododermatitis) after spending the day in grassy/weedy environments.

2. Allergic conjunctivitis, rhinitis or periocular dermatitis - minimize exposure to airborne irritants (e.g. tobacco smoke, aerosols etc.).

3. Mold sensitivities - avoid rooms with high moisture levels (bathroom, basement); decrease numbers of house plants; use a dehumidifier.

4. Pollens - use air conditioners and air filters; avoid fields, keep lawn cut short; rinse dog after trips into grassy/weedy sights; keep dog inside when mowing lawn; keep dog in early in morning and at dusk (when pollen concentrations peak).

5. House dust mite sensitivity - mites concentrated in bedding, stuffed furniture and carpets. Remove carpeting or matting, thorough regular cleaning (high efficiency vacuum). Cover mattresses with plastic; regular washing and thorough drying of bedding. Dog should not sleep on cushioned furniture and be kept in uncarpeted rooms. The documentation and semi-quantitation of house dust mite allergen concentrations are now possible through the use of technologies such as the Mite-T-Fast Allergen Detection System (AVEHO). Once detected, there is the potential for environmental mite control programs such as borate (AVEHO Dust Mite and Flea Control) and mite allergen deactivators (e.g. Allerase Anti-Allegen treatment, AVEHO).

Topical Therapies 1. Shampoos and Conditioners: Shampoos containing oatmeal or oatmeal and

pramoxine (a local anesthetic) may give a few hours of antipruritic activity. A shampoo more recently marketed in the U.S. by Virbac (Allermyl; contains linoleic acid, L-rhamnose, Vitamine E) has performed favorably in this regard. These shampoos are usually followed up with anti-pruritic conditioners to both treat and prevent the development of dry skin which may be a product of the disease or repeated bathing. The author prefers residual conditioners for this purpose: oatmeal (ResiSoothe, Virbac), oatmeal and pramoxine (Resiprox, Virbac) or 1% hydrocortisone (ResiCort, Virbac). The hydrocortisone product appears to have superior anti-pruritic activity. In that many of our atopic patients are prone to recurrent bacterial and Malassezia infections, it is very common for us to use a germicidal shampoo (e.g. Malaseb with chlorhexidine and miconazole; DVM pharmaceuticals) on a maintenance basis. This is then followed by the use of an antipruritic conditioner (e.g. ResiProx, Virbac). The residual conditioner can also be used by itself (without shampoo) between bathings to help reduce pruritus.

2. Topical glucocorticoids can be very beneficial. In the past, the use of 1% hydrocortisone products have been favored by the author (e.g. CortiCalm by DVM, DermaCool-HC by Virbac or ResiCort by Virbac). More recently,

a .015% triamcinolone acetonide spray (Genesis Topical Spray) has been marketed by Virbac as an adjunctive therapy for allergic dermatitis. It is water-like in consistency and odorless. In one well controlled, multi-centre study, reduction in the severity of dermatitis in allergic patients was noted in 65% of patients, versus 24% noted with a placebo (the propylene glycol vehicle). The spray is administered BID for one week, then once daily for one week, then once every other day. Absorption is minimal, but limits have been put on the amount of spray that should be administered during any given day. Polyuria was reported in 3 of 57 dogs treated and polyphagia in 1 of 57 dogs. There was no notation of the exacerbation of pyoderma in treated individuals but this should be closely monitored for. This product has proved very beneficial for better controlling the more focal manifestation of atopic pruritus. In some dogs, it has allowed for control when all other therapies have failed. Now that we have had over two years of experience with this medication, it should be noted that too frequent application over long periods of time (e.g. once every other day for 8 - 12 months) may produce significant regional hair loss, cutaneous atrophy and predisposition to local infections. Enough of the product may be absorbed to contribute to the development of generalized iatrogenic hyperadrenocorticism (e.g. widespread hair loss, cutaneous atrophy). The product must be used with respect!

3. Tacrolimus is an inhibitor of T-lymphocyte activation. It is noted to be 10 - 100 times as potent as cyclosporine. Absorption from the skin is minimal. This product has been shown to be very beneficial in the topical management of atopy in man. It is available commercially as Protopic (Fugisawa; .1%; a 30 gm tube costing about $85.00 to the client). It is initially applied BID. This product may be beneficial for the more focal, at times refractory manifestations of atopy. Its cost precludes use over large areas of the body. Tacrolimus appears to do a better job of reducing the inflammation associated with atopic dermatitis as compared to pruritus, but may work for both. This product appears to be superior to the less costly pimecrolimus (Elidel; Novartis), whose mode of activity is similar to that of tacrolimus.

Glucocorticoids

Glucocorticoids remain the most predictably effective therapies for the management of atopic pruritus and inflammation. Anti-inflammatory dosages are usually used initially (e.g. 0.5 - 1 m/kg/day of prednisone or prednisolone), with dosage tapering indicated by the severity and chronicity of skin changes, to minimize side effects and determine what the lowest dosages required to control symptoms. Glucocorticoids would be an acceptable method of management for shorter term atopic problems (e.g. 4-5 months of each year) - assuming patient tolerance. Alternatives to prednisone /prednisolone include metylprednisolone (reduce incidence of PU/PD) or Temaril-P (5 mg of trimeprazine, an antihistamine and 2 mg of prednisone per tab); may allow for lesser dosages of glucocorticoid because of the antihistamine included. Prior to considering glucocorticoids for longer term maintenance, every effort should be given to provide glucocorticoid alternatives. When this is not possible, the author will usually try to maintain the patient on the lowest, once every other day dose of Temaril-P possible. This is often facilitated by using Temaril-P along with a full, daily dose of another antihistamine such as chlorpheniramine, diphenhydramine, hydroxyzine, amitriptyline, or clemastine. This often allows one to minimize the dose of Temaril-P. Many large breed dogs may be maintained on 1-3 tabs once every other or third day. It is important, even at these low dosages to look for mild signs of iatrogenic hyperadrenocorticism (dry coat / skin; mild hair loss; gradual weight gain; increased propensity to develop bacterial pyoderma; increased propensity to develop urinary tract infections.

Fatty Acids Although controversy still exists as to which fatty acids to use in optimizing anti-pruritic effects, products rich in n-3 fatty acids (cold water fish oils and flaxseed) appear to be favored. Using an n-3 fatty acid product (3 V Caps, DVM) at bottle dosages, significant improvement is seen in 10 - 15% of patients (10 - 90% improvement). A very small study showed superior antipruritic effects with very high dose omega 3 fatty acids (180 mg eicosapentaenoic (EPA)acid and 120 mg docosahexanoic acid (DHA) / 10 lb. body weight per day; Logas et al Vet Dermatology, 1994). A study recently completed at CSU appears to support this data. For those dogs receiving 50 - 85 mg/kg of EPA and 35 - 55 mg/kg DHA (equivalent to 1 Giant breed capsule per 5 kg body weight) or 200 - 335 mg/kg of flaxseed oil per day, 40 - 50% improved by greater than 50%. Complete remission was obtained in 10 - 20%. This suggests that higher dosages of omega 3 fatty acids should be used to initiate/assess therapy (e.g. 2-3 times the bottle dosages). Although it has been suggested that fatty acid containing products should be given at least a 12 week trial before they are critically evaluated, it was noted that most individuals had improved within the first 2-3 weeks of therapy in this study. Deleterious side effects are uncommon but include gastrointestinal upsets, increased pruritus and pancreatitis. Although high dose therapy could conceivably result in decreased neutrophil reactivity, decreased clotting and decreased wound healing, this has not been seen in clinical studies nor with clinical use.

As fat supplements, it is not uncommon for these products to improve coat luster, softness etc., even though the degree of pruritus is not reduced.

Research by Iams has shown that a 5:1 to 10:1 ratio of omega-6 to omega-3 fatty acid in the overall diet may be ideal for management of inflammatory skin disease in the dog. Their diet, formulated to meet these specifications is Eukanuba Veterinary Diets TM Response Formula FpTM for dogs. Our own uncontrolled studies evaluating the efficacy of this diet in 47 atopic dogs showed a greater than 50% reduction in pruritus in 42% of dogs.Antihistamines

Antihistamines appear to benefit about 20 -30% of our atopic patients. Both first generation H1 blockers (e.g. chlorpheniramine, diphenhydramine) and second generation products that fail to cross the blood brain barrier (e.g. loratidine, ceterizine) appear to have similar success rates. It is felt that one cannot predict which, if any antihistamine, will be of help in a given individual. We generally have the owner try several different antihistamines, each for 2 weeks (3 or 4 weeks if the owner is not very observant). The owner notes which antihistamine is being used and what degree of benefit, if any, it may produce. The following are the antihistamines used most frequently in our practice. Those with an asterisk tend to be most effective/cost effective (unless otherwise marked): * Diphenhydramine (25, 50 mg caps) - 2.2 mg/kg BID or TID;* Hydroxyzine HCl (10, 50mg tabs) - 2.2 mg/kg BID or TID ; * Chlorpheniramine (4, 12mg caps) .4 - .8 mg/kg ( .5 mg ) BID to TID ; *Amitryptyline-(10, 25, 50, 75, 100 mg tabs) 2.2 mg/kg BID; *Clemastine (Tavist or generic) - 1.34 mg tabs, .05 mg/kg BID, for dogs under 10 kg 1/2 tab BID; 10 - 25 kg, 1 tab BID, bigger, 1 1/2 tab BID; Cyproheptadine - (4 mg tabs) .25 - .5 mg/kg TID; Doxepin HCl-(10, 25, 50, 75, 100, 150 mg) .5- 1.0 mg/kg BID; Trimeprazine tartrate - 2.5 - 5 mg/dog TID (expensive). Which is the most effective? Some studies have suggested clemastine; another recent study suggested hydroxyzine and diphenhydramine. The author has best results with chlorpheniramine and hydroxyzine. H 1 blockers that have antihistaminic, antichollinergic, sedative and local anesthetic effects. They must be used with caution, if at all, in the presence of liver disease, glaucoma, urinary retention, gastrointestinal atony and pregnancy.

The newer, non-sedating antihistamines include cetirizine ( 10 mg/day/animal < 25 kg and 10 mg BID > 25 kg), loratidine (0.5-1.0 mg/kg/day) and astemazole (.25

mg/kg q24hr). It has been suggested that cetirizine may be the most effective of this group. Combinations of antihistamines may be of benefit when the individual antihistamines themselves appear to have failed. The author has most commonly used chlorpheniramine along with hydroxyzine or amitriptyline or trimeprazine (in Temaril-P).

Pentoxifylline

Pentoxifylline (a phosphodiesterase inhibitor) has been noted to reduce the pruritus and erythema associated with atopy at a dosage of 10 mg/kg BID, although TID administration at dosages as high as 20 - 25 mg/kg may be more beneficial. The author has, in general, been disappointed with this drug as a monotherapy for atopy. It may help to reduce steroid dosages in patients on glucocorticoids, and may work synergistically with antihistamines. It is therefore usually used as part of a combination therapy, especially when other more conventional therapies have failed. There is some suggestion that some generics may not be as effective and the trade name product (Trental). This may suggest the use of the trade name product, at lest for an initial trial period of one month. If it is effective, the generic can then be tried. The author routinely uses generic products to initiate therapy.

Cyclosporine

Oral cyclosporine is now available to Veterinarians in the United States as a veterinary product (Atopica, Novartis), specifically marketed as a therapy for canine atopy. Oral cyclosporine has now been used for several years in the management of atopy in the dog. Cyclosporin-A (Neoral ® , Sandoz) is most commonly used at a dose of 5mg/kg/day. It has been noted to produce good to excellent results in 70 - 80% of cases. The overall beneficial effects have been shown to be similar to those of prednisolone or methylprednisolone, without the attendant deleterious side effects of the steroid. The major side effect encountered is gastrointestinal upset (vomition, diarrhea, flatulence, abdominal cramping - with vomition being most common). The incidence of vomition may be minimized by gradually working up to the maintenance dose over several days. Cyclosporine should be given on an empty stomach (at least 2 hours before feeding) to enhance absorption. However, if vomition is noted, the drug should be stopped until this side effect has resolved and can be tried again with a small amount of food. Other side effects reported in dogs include gingival hyperplasia, papillomatosis, bacteriuria, bacterial pyoderma, anorexia, nephropathies, bone marrow suppression and a lymphoplasmacytic dermatosis. Trial therapy should be 45 - 60 days. It may take this long to see the maximal benefits of the drug. Once a beneficial effect has been noted, attempts can be made to reduce the daily dosage, or treat once every other day. It has been shown that maintenance may be achieved with either lower daily dosages or less frequent administrations. In this study (Olivry T et al, Proc. AAVD/ACVD, 2003), oral cyclospirne was reduced monthly to 2.5 and 1.25 mg/kg once 50% and 75% reduction of signs were achieved. 12 of 15 dogs were able to be controlled a these dosages. In another group of dogs, a daily dose of 5 mg/kg was reduced to every 2 and 4 days once patients improved by 50% and 75%, respectively. 13 of 15 individuals were able to be controlled. In yet another study of 51 dogs who were treated for 6-30 months, 15% were able to be maintained on 2-3 days per week of cyclosporine, 20% on 4-5 days per week, and 20% required daily therapy (Radowiz S et al, Proc. AAVD/ACVD 2003). It is very interesting to note that in both studies, a significant number of patients were able to have their oral cyclosporine eventually stopped, with a complete remission of disease (no recurrence) (Olivry - 10% of cases; Radowiz - 24%). In that cyclosporine is expensive, it has been used in conjunction with ketoconazole to increase the blood concentrations of the cyclosporine. The mechanism for this decrease in clearance is probably a combination of the inhibition of cytochrome P-450 in the intestine and liver and the inhibition of

intestinal p-glycoprotein that would ordinarily pump oral cyclosporine into the intestine. Optimal dosages and frequencies of ketoconazole have yet to be established in atopic dogs. We tend to start with 2.5 mg/kg cyclosporine per day along with 5.0 - 10 mg/kg ketoconazole once per day. A higher dose of ketoconazole (i.e. 10 mg/kg/day) may be associated with higher circulating cyclosporine concentrations and greater anti-pruritic benefits. The ketoconazole is usually given with a small amount of food, but the cyclosporine is usually given 2 hours before or after giving this small amount of food.

Behavior Component to Atopic Pruritus? - There has been a suggestion that a subset of both atopic dogs may be pruritic in response to anxiety and/or another central trigger. "These repetitive behaviors are believed to be controlled by endogenous opioid release. Dextromethorphan is an opioid antagonist that does not work by binding and blocking opioid receptors but rather by blocking receptors for N-methyl-d-aspartate, which are found in the brain and spinal cord and mediate various sensations, including pain". Dextromethorphan has been used to significantly benefit some dogs in this fashion (2 mg/kg PO q 12 hours); in one study, 11 of 12 dogs had some degree of improvement. Dextromethorphan use should be reserved for those atopic patients that fail more traditional anti-pruritic therapy and (ideally), where there is suggestion that the behaviors are repetitive and anxiety-induced.

Hyposensitization

Hyposensitization is noted to benefit 60 - 70% of cases (good to excellent results).

"Rush" immunotherarpy, which involves giving all the induction dosages in the hyposensitizing protocol in one day appears to produce a more rapid onset of benefit from hyposensitization and possibly a higher over success rate.

Over the long term, 50 - 70% of our patients on hyposensitization require additional medication (antihistamine steroids and/or fatty acids) to control allergic signs during part or all of the year.

The majority of our patients on maintenance hyposensitiztion get their shots every 1-2 weeks during the allergy season. For patients who derive only transient benefits from a given shot (2-3 days), we divide our solutions and give .5 cc twice weekly, or even smaller volumes up to three times a week (e.g. .2 cc three times weekly).

It is also very important to monitor for increased pruritus following a given shot. Affected individuals may actually have their allergy signs significantly worsened if they react to the hyposensitization solution. If such is the case, we reduce the volume of solution to that which did not produce a reaction. Patients noted to have reactions to shots appear to have an overall better chance of deriving benefit from the shots, assuming the volume and frequency of solution is managed appropriately.

It is interesting to note that in one recent study (Power H et al,), 29% of patients who discontinued hyposensitization shots did so because the atopy went in to spontaneous remission. We quote a 20 - 30% chance that individuals with come off hyposensitization after at least 2-3 years on the desensitizing protocol.

FELINE ATOPY: AN UPDATE

In the older Veterinary literature, it has often been suggested that the incidence of atopy is similar to that of food sensitivity in the cat. However, in our clinic, for

cats showing the clinical signs listed below, about 70% are noted to be atopic and 30% food sensitive.

Feline atopy is associated with a myriad of clinical signs. These may include: Maracle

1. Alopecia with or without dermatitis due to self trauma (may be a symmetric, self - induced alopecia; higher prevalence areas tend to be the ventral abdomen, caudal thighs, dorso-medial forelimbs)

2. Pruritus directed at and restricted to the head and/or neck 3. Pruritic miliary dermatitis (lesions most commonly over the back, sides and

head) 4. Eosinophilic plaques (pruritic) - most commonly over the medial thighs and

ventral abdomen, but may be found over any area of the body 5. Indolent ulcer - upper lip or lips; may be the only manifestation of atopy in

a given individual 6. Eosinophilic granuloma - variable pruritus; lesions may be found anywhere

over the body; higher incidence in chin area, caudal thighs (linear granuloma) and oral cavity (hard and soft palate).

7. It is possible to see any of the manifestations of the eosinophilic granuloma complex (eosinophilic plaques, indolent ulcer, eosinophilic granuloma) in the same cat.

8. Recurrent or persistent otitis externa; pruritic lesions usually also noted in other areas of body, but predominant area of involvement may be the ears. Athough the otitis is usually bilateral, unilateral involvement is possible. We have seen "flares" of otitis externa result in perforation of the tympana, apparently without the presence of secondary bacterial or yeast infection (pressure changes within the middle ear?).

9. Pruritic lesions may predominate in the chin and perioral region as diffuse erythema and the accumulation of dark exudates, giving the impression of feline acne; however, when clipped, classic comedo formation is not noted.

10. May exacerbate true feline acne lesions (comedoes) 11. Secondary bacterial pyoderma occurs but is less common than in the dog. 12. Secondary Malassezia infections are noted, but are less common than in

the dog. They tend to predominate in the facial (folds, lip margins, chin) and foot areas (interdigital).

13. Rhinitis, conjunctivitis 14. Asthma

Feline atopy may begin as either a seasonal or non-seasonal problem. Seasonal presentations may progress to year round manifestations with time.

Feline atopy is largely diagnosed by rule out. The major differential diagnoses to be considered include flea bite hypersensitivity, food sensitivity, cheyletiella, demodicosis and dermatophytosis. It is not uncommon to see a peripheral eosinophilia and basophilia. Skin biopsies show inflammatory changes that not uncommonly reveal increased numbers of mast cells and eosinophils. The documentation of offending allergens is achieved either with intradermal skin testing, which tends to be more difficult to read than in the dog and in vitro, serologic testing. At present both RAST and ELISA tests are available for use in the cat. In one study, there was poor correlation between IDST and commercial ELISA data. In another study, similar success to hyposensitization was seen based on ELISA or IDT data . Further comments regarding the efficacy of this type of testing awaits controlled studies but it is important to note that many Veterinary Dermatologists have migrated to doing serologic testing in the cat as their choice diagnostic for defining offending allergens. This likely has most to do with its ease of performance compared to doing skin tests. It is important to note that, because of the potential for false positive results, this type of testing should not be done to diagnose atopy in the cat.

Therapy

The therapy of feline atopy should always include the documentation and treatment of secondary bacterial or Malassezia infections. These are best defined by cytologic examination.

Because glucocorticoids are well tolerated in the cat, they tend to be the cornerstone of therapy. However, as the disease becomes more chronic and severe, it is not uncommon to have the patient require higher dosages, more frequent dosage administrations or more potent glucocorticoids to maintain comfort. We are of the impression that prednisolone tends to be more effective than equal dosages of prednisone in some cats, and for this reason, in choosing between these drugs, we would choose to routinely use prednisolone in cats. Cats are often started on 1 - 2 mg/kg/day of prednisolone. "Depo" steroids are acceptable for periodic administration (ideally keep frequency of administration to less than once every 6-8 weeks - methylprednisolone acetate or triamcinolone acetonide). For patients refractory to prednisolone consideration should be given to using the longer acting, more potent oral dexamethasone (.1 - .2 m/kg/day) or triancinolone acetonide (.5 - 1 mg/kg/day). Emphasis should always be placed on reducing dosages to the least frequent administration possible.

Fatty acids (omega 3 and 6) such as DVM Derm Caps Liquid or 3V caps (omega 3) benefit approximately 20 - 30% of cases (some quote 30 - 50%). Many cats, however, refuse to eat the fatty acids.

The antihistamines that have been of most benefit for in our hands for treating feline atopy are chlorpheniramine (2-4 mg/cat q 12 hrs) or amitriptyline ( 5-10 mg/cat q 12 - 24 hrs. Amitriptyline may cause significant sedation, ataxia etc.; cats may salivate excessively when it is given. The later can be circumvented by using amitriptyline powder mixed in fish/cod liver oil. Other antihistamines to be tried include clemastine fumarate (.34 - .68 mg/cat BID), ceterizine (.5 - 1 mg/kg or 5 mg/cat) or cyproheptadine (2 mg/cat BID; may cause polyphagia and behavioral effects). Each is tried for 3 weeks.

Hyposensitization has been reported to benefit anywhere from 45% to 75% of cases. Our success rate has been in the 60 -70% range. Protocols using aqueous allegens are similar to those used for the dog. The author uses the same frequency of administration, but only 1/2 the volumes. One recently published study reported the benefits of hyposensitized based on RAST data. The numbers of patients with various manifestations of atopy and the percentage of patients who improve by greater than 50% included : hair loss - 29cats/53%; military dermatitis - 23cats/76%; eosinophilic plaque - 10 cats/ 73%; indolent ulcer - 6 cats/95%; linear granuloma - 3 cast/100%; otitis externa - 4 cats/65%; Asthma - 4 cats/90%

Oral cyclosporine has been noted to work well in the management of atopic dermatitis in the cat. Cats are generally treated with 5 - 7 1/2 mg/kg/day. In one study, eosinophilic plaques and eosinophilic granulomas were put in to remission within 30 - 60 days. 3 cats with indolent ulcers had only partial responses. Cyclosporin at this dosage appears to be tolerated reasonably well . GI upsets (nausea, vomition, anorhexia) are relatively common. If possible, we gradually increase our dosages over several days, prior to getting to our maintenance dose (above). If GI problems are encountered, the drug is stopped until the signs have abated and it is then re-instituted … given with a small amount of food. We have seen apparently latent toxoplasmosis exacerbated while on this therapy (likely because of the immunosuppressive effect of cyclosporine .. something to be aware of!

Chlorambucil has also been of benefit (usually along with steroids) in treating

refractory atopy. Recommended dose is 0.1 - 0.2 mg/kg q 24 hrs until 75% improvement in clinical signs, then this dose every other day. Adverse effects to be monitored for include hepatotoxicity and bone marrow suppression.

Megestrol acetate may be considered a "last ditch" alternative for treating feline atopy, in light of potential side effects ( polyphagia / weight gain, PU/PD, personality and behavioral changes, pyometra or stump pyometra, mammary hyperplasia, mammary neoplasia, diabetes mellitus and adrenal suppression). Remission of clinical signs can often be achieved with an oral dose of 2.5 - 5.0 mg/cat every 48 hours for 1-3 weeks. This is followed by weekly maintenance dosages.

CANINE AND FELINE FOOD SENSITIVITIES

Adverse reactions to foods are generally divided into various subsets based on pathomechanism. Those that are of most significance from a dermatology point of view include food intolerance and food allergy. Food intolerances mimic food allergies, but can occur on first exposure to a dietary ingredient and involve non-immunologic mechanisms. They may be further subdivided into food idiosyncrasy and pharmacologic reactions to foods. Idiosyncratic reactions to various ingredients in foods are often described in human beings. Sulfites, monosodium glutamate, tartrazine, azo and noazo dies, benzoates, parabens and spices have all been incriminated. In the case of azo or nonazo dyes, the mechanism may involve histamine release from leukocytes. Similar reactions are suspected to occur in dogs and cats but are poorly documented. Food ingredients may also be associated with the pharmacologic action of various ingredients in foods (i.e. vasoactive amines such as histamine which can increase in spoiled scombroid fish such as tuna, mackerel, skipjack and bonito). Food allergies are immunologically mediated reactions to water soluble glycoproteins that have molecular weights ranging from 10,000 - 60,000 daltons. This data comes largely from experiences with food sensitivities in man, but appear to be applicable to the dog and cat.

CANINE ADVERSE REACTIONS TO FOODS

Allergic to what? In the dog, adverse reactions to beef, diary products and wheat account for 2/3 of the reported cases. Reactions to chicken, chicken egg, lamb or soy account for another 25%. Other glycoproteins that have been incriminated include corn, oatmeal, pasta, pork, fish, turkey, potatoes, rabbit, rice flour, rice, artificial food additives (gum carrageenan) and food preservatives . In one study of 25 food allergic dogs, 80% of affected dogs were reactive to 1 or 2 allergens in the diet. 64% were sensitive to two or more allergens. The mean number of allergens reacted to was 2.4.

Incidence: controversial: 3-10% of all canine allergic hypersensitivity (excluding parasitic allergy). There does appear to be a significant regional difference in the incidence of food sensitivities across the US (i.e. more common in the east than the southwest etc.). Concurrent flea bite hypersensitivity or atopy may occur in up to 75% of cases.

Clinical Signs: In the dog, no age or sex predilections are noted, although many cases tend to occur in younger dogs (33% - 52% less than 1 year of age in reports from various studies). The index of suspicion for food hypersensitivity is above that of atopic disease when pruritus occurs in dogs under six months of age. Breeds predisposed include American cocker spaniel, English Springer spaniel, Labrador retriever, collies, miniature schnauzer, Chinese Shar pei, poodle, west highland white terrier, Wheaten terrier, Boxer, dachshund, Dalmation, lhasa apso, German shepherd and Golden retriever.

Pruritus is nonseasonal, although it may wax and wane if exposure to the

offending allergen is episodic. The hallmark clinical manifestation is pruritus (most commonly ears, rump, distal limbs, axillae, and groin). Secondary seborrheic, bacterial and Malassezia problems are common. Symptoms may be restricted to just an otitis externa in as many as 20-25% of cases. Food colorants and other additives have been suggested to cause erythema multiforme and other "drug-like" skin eruptions. Lesions include erythematous macules, and papules that spread to produce annular target and arciform lesions. Involvement of the oral and nasal mucosa, pinnae, axilla and groin are common. Other associations include recurrent bacterial pyoderma (with or without pruritus), eosinophilic vasculitis (presenting as urticaria or any of the various lesions associated with vasculitis), malaise, dullness and rarely seizures. Gastrointestinal signs (vomiting, diarrhea, colic) are noted in 10-15%. Gastrointestinal signs may be characterized by only an increased frequency of bowel movements.

Diagnosis and Therapy: The histologic changes associated with food sensitivity in the dog are relatively nonspecific and consist of a superficial perivascular dermatitis with mononuclear cells or neutrophils predominating. Increased eosinophils are occasionally present. There is one report which suggests that the presence of eosinophilic infiltrates is more closely associated with a diagnosis of food sensitivity than atopy in the dog (when evaluated in a flea free environment). Serologic testing for food allergies (radioallergosorbent RAST or ELISA testing) and intradermal skin testing have shown poor predicatability and poor correlation with response to provocative challenge and are not recommended for diagnostic purposes.

Home prepared diets appear to be closest to 100% effective in determining the presence of food sensitivity. There are several reports in the literature of both dogs and cats who have manifest signs of food sensitivity when fed a commercial diet consisting of the same ingredients offered in a home prepared form. Home prepared diets that the author favors include a single, novel carbohydrate (potato, yams, pinto bean) combined with a single, novel protein (venison, duck, rabbit, ostrich, kangaroo). We generally feed one cup per ten pounds body weight of the mix per day; _ - 1/3 of this mix is usually the protein component. It is recognized that these diets are nutritionally inadequate for growth and maintenance. Homemade foods lack a source of calcium, essential fatty acids, certain vitamins and various micronutrients. These homemade diets are not recommended for trial purposes in growing animals for any longer than three weeks unless they have been balanced with a non-flavored, additive free vitamin, calcium/phosporous and a source of essential fatty acids such as vegetable oil. Vegetable oils are not likely to contribute to allergic symptoms. Because of the inconvenience factor required in home formulating balanced diets, the author tends to use commercial restrictive diets for most growing animals.

Commercial diets currently available are quite good, but it is well known that no commercial diet works for all food allergic individuals. An estimate of about an 80% - 85% chance of success with any given diet seems reasonable based on data available to date. Commercial restrictive diets can generally be divided into two categories:

a. Novel protein diets: e.g. Innovative Veterinary Diets duck, venison, rabbit and lamb and potato, Iams Eukanuba Veterinary Diets Response Formula FP (fish and potato; has additional omega 3 fatty acids which have been noted to benefit about 40% of atopic dogs; this must be taken into consideration when interpreting response), Iams Eukanuba Veterinary Diets Response Formula KO (kangaroo and oat), Hills Prescription Diet Canine d/d (rice and egg), Hills Prescription Diet canine d/d (Rice and Salmon; dry), Hills Prescription Diet Canine d/d (whitefish and rice;canned ) etc.

b. Protein hydrolysates: it is known in man that major food allergens are typically large glycoproteins of molecular weight greater than 12,000

Daltons. Hydrolysate diets have had their proteins chopped into smaller peptides which theoretically render them less allergenic. Some diets contain only hydrolyzed protein sources, while others contain both hydrolyzed and intact protein sources. Examples include Purina HA (hydrolyzed soy protein, corn starch), Hills Prescription diet z/d Ultra Allergen Free (starch, hydrolyzed chicken liver, hydrolyzed chicken), Prescription diet canine z/d low allergen (potato, hydrolyzed chicken liver, hydrolyzed chicken), DVM Exclude (novel carbohydrate is pinto beans ad oats, hydrolyzed protein is casein and chicken liver). Some data is available on the efficacy of these diets. In one recent study (Rosser ER , Proc. AAVD/ACVD 2001), 18 of 19 proven food sensitive dogs (specific offending allergens not specified) fed the DVM Exclude diet failed to show any exacerbation of pruritus. In another study, 21 of 23 proven food allergic dogs (allergens not specified) were noted to respond to the Purina HA diet. In our own studies, 13 food allergic dogs were fed the z/d ultra allergen free diet and none had an exacerbation of pruritus. Only recently has data been generated on the efficacy of one of these diets when fed to individuals known to be allergic to the protein in the diet (Purina Veterinary Diet HA Formula; Beale, DM, Proc. AAVD/ ACVD, 2001). In this study of 10 dogs with corn or soy sensitivities or both, pruritus was reduced 50% (in soy allergic dogs = 6) to 80% (in corn allergic dogs =4) compared to dogs fed intact corn or soy. It would appear that, even in corn and soy sensitive individuals, pruritus and erythema could be expected to improve significantly on the diet, but not necessarily resolve. This would suggest that these diets may also not be "perfect" in their ability to totally assess or treat food sensitive individuals. If a partial response is noted to a hydrolysate diet, before working the dog up for other allergy types to explain the residual pruritus, it may be prudent to switch to a home prepared diet or another restrictive diet to complete the diet trial.

c. At this time, the answer to the question, "which is the best commercial restrictive diet" remains open for debate. Until more data is available on clinical trials using the hydrolysate diets, it is probably best to continue to state that there is no commercial diet that will work for all food sensitive individuals. When food sensitivity remains a possibility following the use of a commercial diet trial (i.e. diagnostics or therapies for atopy do not appear to be benefiting the skin disease), then strong consideration should be given to trying a home prepared restrictive diet to better rule out a food sensitivity component to the problem.

Diet trial duration is generally 8 weeks. Complete resolution of signs may require 10 to 13 weeks. Every effort must be made to keep the diet trial strict (no other foods, treats, flavored chew toys, flavored heartworm preventative etc.). Patients are ideally re-checked 1-2 times during the diet trial to assure compliance and examine for the presence secondary infections etc. that may complicate interpretation of the diet. Compliance may be enhanced by having the owners maintain a daily log of "degree of pruritus" and amount/types of food fed. If a response to the diet is noted, the diet should be continued until maximal benefit is achieved. A partial response (e.g. 50%) may suggest the presence of intercurrent causes of pruritus (e.g. atopy) unless the diet trial is with a hydrolysate (see above under hydrolysate diets). It is very important that potentially pruritic pyoderma and/or Malassezia infections be cleared up and controlled, early in the trial diet. It is not uncommon to continue antibiotic therapy or Malassezia topical treatment throughout the diet trial to prevent exacerbation of infection during the trial. The effect of the diet is confirmed by challenge (with the previous diet). Exacerbations of pruritus are generally noted within the first week, but may take as long as 10 - 14 days. In the event of an exacerbation of signs, re-institution of the restrictive diet usually produces a more prompt response than is encountered during the trialing period. If there is a desire to define the source of the allergy, then single protein sources can be added in to

the basal diet at a frequency of one every 10 - 14 days. This data may allow for the selection of other commercial diets that can be fed in the future.

The signs associated with food sensitivities are variably responsive to glucocorticoids (some may be resistant to anti-inflammatory dosages; some may be very responsive to even low dosages). Antihistamine therapy appears to be less successful when compared to treating atopy in the dog.

FELINE ADVERSE REACTIONS TO FOODS Allergic to What? Adverse reactions to beef, dairy products (milk, cheese) and fish have accounted for nearly 90% of the reported cases in cats. Others include pork, chicken, rabbit, horse meat, lamb, eggs, cam juice and cod liver oil.

Incidence: In one group of 25 allergic cats, flea bite hypersensitivity was seen in 70%, food sensitivity in 17% and atopy in 13%. In our practice, we feel that food sensitivity and atopy are of about equal incidence. Siamese or Siamese crosses may be at increased risk.

Clinical Signs: Pruritus is present in 100% of cases. Pruritus most commonly affects the face, head, pinnae and neck or combinations thereof. Pruritus may also be generalized or restricted to other areas of the body (e.g. racing stripe down the back). Other manifestations include self induced alopecia, military dermatitis and any of the manifestations of the eosinophilic granuloma complex (indolent ulcer, eosinophilic plaque, eosinophilic granuloma). There are rare reports of an exfoliative dermatitis characterized histologically by a lymphocytic mural folliculitis and an erythematous papulopustular eruption characterized by eosinophilic folliculitis and furunculosis related to food sensitivities in the cat. Angioedema, urticaria and conjunctivitis, sneezing, malaise, dullness and a peripheral lymphadenopathy have also been noted. Gastrointestinal signs (vomition, diarrhea) are noted in 10 - 15% of cases. Up to 25% of cases have concurrent hypersensitivities (atopy or flea bite hypersensitivity).

Diagnosis and Therapy: The histopathology of food sensitivity most commonly involves a superficial and/or deep perivascular dermatitis wherein eosinophils are the dominant inflammatory cell type. Mast cells are commonly increased and may be the prominent cell type noted. A peripheral eosinophilia may be seen in as many as 50% of cases. The diagnosis is confirmed by assessing response to a restrictive diet. Home prepared diets are again most predictably effective. Single, novel protein sources include lamb or ham baby food, ham, ostrich, rabbit, venison, duck. The protein source may be fed alone or blended with potato or rice. For the purposes of a diet trial (8 weeks), balancing the diet may not be necessary. For long term feeding, however, supplementation with taurine tablets, dicalcium phosphate, safflower oil and a multiple vitamin is recommended. Alternatively, commercial restrictive diets may also be fed. As for the dog, no commercial diet will likely be beneficial for all food allergic cats. Novel protein diets such as the Innovative Veterinary Diets (lamb, rabbit, duck, venison) are used by the author. They have the advantage of coming as both dry and canned foods to help satisfy picky appetites. Hydrolysate diets are also available (Prescrition Diet Feline a/d low allergen (rice, hydrolyzed chicken liver, hydrolyzed chicken).

Cats with food sensitivities are noted to be variably responsive to glucocorticoids (50% may not respond). Response to antihistamines also appears to be generally poor.

A "MINI" COURSE IN OTOLOGYRod A.W. Rosychuk DVM, DACVIM Colorado State University

NORMAL ANATOMY AND PHYSIOLOGY OF THE EAR

The ear canal in the dog and cat is divided into a vertical segment that is contiguous with the pinna and a horizontal segment that extends to the tympanic membrane. The horizontal and vertical canals are largely surrounded by cartilage. However, adjacent to the tympanum, the horizontal canal is supported by bone. The ear canals are lined by skin containing hair follicles, sebaceous glands in the superficial dermis and fewer small modified apocrine (ceruminous) glands in the deeper dermis. The number of hair follicles, sebaceous glands and apocrine glands are more numerous in the vertical than horizontal canal in the dog. Hair follicle density in the horizontal canal varies with breed. Hairs may be seen growing just adjacent to the TM in normal dogs. Cerumen consists of desquamated cornocytes, apocrine secretions, and sebaceous secretions. It is a mixture of proteins, lipids, amino acids and mineral ions. Normal ceruminous secretions facilitate trapping foreign material in the ear and have inherent antibacterial and antifungal activity. The self cleaning function of the canals is achieved through a process of epithelial migration. Epithelial cells are noted to grow laterally from the tympanum (area around the manubrium of the malleus).

The tympanic membrane of the dog is made up of the pars flaccida, a small area of the dorsolateral tympanum which is relatively flaccid, vascular and appears to heal rapidly after perforation and the large pars tensa which is under considerable tension and, once perforated, takes longer to heal. Following complete destruction of the pars tensa in normal dogs, complete regrowth is noted within 21-35 days. The periphery of the tympanum attaches to the annulus fibrocartilagenous which is a fibrocartilagenous ring that attaches to the surrounding bone. The manubrium of the malleus is situated within the fibrous layer of the tympanum. It is white and reverse"C" shaped with the open end of the reverse "C" pointed towards the nose. Tension on this structure gives the tympanum a mildly concave outer contour. The tympanum is oriented at about a 30 - 45 degree angle from perpendicular (dorsal to ventral).

The middle ear of the dog and cat is separated in to three sections: the epitympanic bulla, which is the most dorsal space in the middle ear, housing the ossicles; the tympanic cavity which is that area immediately medial to the tympanum and the tympanic bulla which is immediately ventral to this and is partially separated from the tympanic cavity in the dog by a ridge of bone (variable width from individual to individual). In the cat, the tymapic bulla is separated from the tympanic cavity by a bony plate that is essentially complete but for a small hole in the center of the plate (allowing for communication between the bulla and the tympanic cavity). The middle ear is lined by a respiratory -like epithelium (ciliated columnar cells with some mucous producing goblet cells). The middle ear has a normal bacterial flora. The middle ear communicates with the back of the pharynx through the auditory canal (originates in the anterior medial aspect of the epitympanic recess) which allows for equalization of air pressure across the tympanum.

Normal Canine Tympanic Membrane

THE PATHOGENESIS OF OTITIS EXTERNA AND OTITIS MEDIA

PATHOGENESIS OF OTITIS EXTERNA The successful management of otitis externa is very dependent on an understanding of the pathogenesis of the disease.

Primary factors are those which are capable of initiating inflammation within ears (e.g. allergies). Predisposing factors are those which make the ear more prone to the development of inflammation (e.g. pendulous pinna, excessive moisture in ears) and perpetuating factors are those which are capable of perpetuating the otitis even if the primary factors have been removed/resolved (e.g. opportunistic infections with bacteria and/or yeast).

It is true that with the majority of acute cases of otitis externa seen in practice, symptomatic therapy (cleansing and the use of a broad spectrum topical preparation containing a glucocorticoid, antibiotic and antifungal) will often resolve the otitis and the primary factor/factors responsible for initiating the inflammation will never be known. However, when dealing with chronic or recurrent cases of otitis externa, it becomes imperative to return to the list of primary factors and make sure each is considered. Only through the delineation of these underlying pathologic states can rational therapies be established to resolve or control these particularly difficult cases.

Primary Factors Factors capable of initiating inflammation within ears.

1. Parasites a. Otodectes cynotis - reported to cause approximately 50% of otitis

externa in cats, 5- 10% of cases in dogs. b. Otobius megninii - spinous ear tick of the dog is found mainly in the

southwestern United States. If untreated, the larva may remain in the ear for up to 7 months before molting and falling from the ear.

2. Foreign bodies: grass awns, foxtails, dirt, debris (e.g. "wad" of debris lodged in the horizontal canal adjacent to the tympanum).

3. Hypersensitivities a. Atopy - 80% -85% of canine atopics have otitis externa. In on study

(Muse R. et al, Proc. AAVD/ACVD, 1996) otitis was the initial sign of allergic disease in 25% of atopics. Only 3-5% of atopics will manifest as an otitis externa only (without other cutaneous signs of atopy eventaually developing). Primary area of the ear affected: proximal pinna, proximal vertical canal with rest of canals relatively less involved. Horizontal canal is more likely to be involved with chronicity and/or secondary infections. Atopic otitis is the most common cause of secondary Malassezia infections. It is also one of the more common underlying associations with aural hematomas. The otitis is generally glucocorticoid responsive. Atpic otitis externa appears to be less common in the cat. Diagnosis: Rule out, ID skin test or in vitro serologic testing.

b. Food sensitivities - Otitis externa is commonly associated with food sensitivities in the dog. It has been suggested that as many as 20% of food allergic dogs may manifest as only a bilateral otitis externa. Distribution of changes in the ear is as for atopy. Food sensitivities appear to be a relatively uncommon cause of otitis externa in the cat. Diagnosis: Assessing response to a restrictive diet trial. Whenever possible, secondary ear infections should be resolved prior to or during the early stages of the trial restrictive diet. Clinical/otoscopic/cytologic examinations should be repeated every 3 weeks during the diet trial.

c. Contact hypersensitivities - neomycin (most common), propylene glycol, others? Patient often shows initial improvement on medication, then has a "flare" of otitis in the face of therapy. Diagnosis: cytology may show increased neutrophils, where neutrophils were not part of the initial cytologic findings; response to discontinuation of medication.

d. Irritants: signs similar to those noted for contact hypersensitivities. e. Drug eruption f. Flea bite hypersensitivity: uncommon to see otitis as a

manifestation of FBH. In one recent study (Muse R, Proc. AAVD/ACVD, 1996) 4 of 17 dogs had a concurrent otitis externa.

4. Keratinization/sebaceous gland disorders - produce a ceruminous or seborrheic otitis. Abnormalities of the stratum corneum (hyperkeratosis) produce a microenvironment that predisposes to secondary bacterial and yeast infection. Abnormal qualitative and quantitative cerumen accumlations may be irritating in that they may contain higher concentrations of fatty acids which are potentially irritating. Bacteria and yeast may also break down waxes to more irritating fatty acids. Clinically characterized by either dry, scaly ears or oily/waxy ears with mild inflammation.

a. Endocrinopathies - hypothyroidism; sex hormone imbalances - hyperestrogenism or hyperprogestinism in females, Sertoli cell tumors in males). Patients usually have more generalized cutaneous or systemic involvement which suggest these diseaes.

b. Idiopathic seborrhea (esp. cocker spaniel) - oily/waxy ears with mild inflammation; usually see other cutaneous involvement.

c. Sebaceous adenitis - dry, scaly, mildly to moderately inflamed ears. In many instances, the otitis externa associated with sebaceous adenitis is relatively well tolerated. Standard poodles, Samoyeds and Akitas are predisposed but any breed is susceptible. Patients generally have other skin lesions. Diagnosis by biopsy (pyogranulomatous inflammation destroying sebaceous glands; marked epidermal and follicular hyperkeratosis).

d. Ceruminous otitis in cats - quite common to see increased amounts of oily secretions in the ears of cats. This appears to be well tolerated by most; significance unknown. On occasion, this ceruminous accumulation does appear to predispose to recurrent

infections (e.g. Malassezia). 5. Autoimmune diseases- Pemphigus foliaceus, pemphigus vulgaris, systemic

lupus erythematosus, idiopathic vasculitis in the dog; pemphigus foliaceus, discoid lupus erythematosus in the cat. Autoimmune diseases usually affect the pinna rather than the canals. Patients almost always have other cutaneous involvement as well. Diagnosis: biopsy.

6. Zinc-responsive dermatoses - usually affect the pinna but on occasion the canals are involved. Siberian husky, malamute, Doberman pincher are predisposed but can see this problem in other breeds. Diagnosis: histopathology (parakeratotic hyperkeratosis) and response to trial zinc therapy.

7. Viral diseases - canine distemper virus 8. Juvenile cellulitis - acute inflammatory exudative otitis externa affecting

primarily the muzzle and periocular regions. Marked submandibular and prescapular lymphadenopathy.Golden retriever, dachshund, yellow retriever, Lhasa apso predisposed but other breeds potentially involved. Age of onset - 3 weeks to six months of age. Hypersensitivity disorder due to unknown. Diagnosis: clinical appearance, rule out, biopsy.

9. Idiopathic hyperplastic/inflammatory otitis externa of American cocker spaniels - relentless inflammatory otitis that often begins at a relatively young age Affected individuals often devoid of other skin problems. With chronicity, proceeds to proliferative changes within the canals and calcification of the auricular cartilages. Must be differentiated from allergic otitis, seborrheic otitis.

10. Inflammatory polyps in the cat - etiology unknown. Attempts to find a viral etiology have, to date, been unsuccessful (herpes and calici virus). Unilateral or bilateral. May occur in any aged cat. Most commonly grow from the middle ear, then extend either through the tympanum into the horizontal canal, or down the auditory canal.

*PREDISPOSING FACTORS - Produce an environment conducive to the development of otitis externa.

1. Anatomical predispositions a. Pendulous pinna - increased relative humidity b. Dense hair in the ear canals (see below) c. Dense coat at entrance to the vertical canal (spaniel breeds) d. Stenotic ear canals (some chow chows, English bulldogs may have

narrowing of horizontal canal; Shar pei's have a sharp angle at junction of vertical and horizontal canal and also mucin accumulations that narrow the entrance to the vertical canal).

2. Excessive moisture in ears (high humidity climate, bathing, swimming - results in maceration). Swimmer's ear (although many of these dogs appear to have underlying allergies that function as primary factors to initiate inflammation within the ears).

3. Increased environmental temperature (contributes to regional variations in incidence of otitis externa?).

4. Hair in ears - Generally not a problem unless a concurrent otitis externa present. Therefore, routine plucking is not recommended. However, if otitis is present, may result in retention of debris and ceruminous secretions; may alter aeration in ears predisposing to increased moisture and associated maceration and therefore should be reduced where possible.

5. Iatrogenic irritation - hair plucking, excessive cleaning, irritant topicals. 6. Obstructive lesions in the ear (e.g. neoplasia, granulation) - prevent proper

aeration and drainage and allow for the accumulation of potentially irritating debris; produce a microenvironment that is conducive to secondary bacterial and yeast infections.

a. proliferative changes in ears. b. inflammatory polyps in cats. May originate from the lining of the

tympanic cavity, auditory canal or nasopharynx.

c. Neoplasia - Dogs: ceruminous gland adenomas and carcinomas (adenomas more common than carcinomas), papillomas, basal cell carcinomas, squamous cell carcinomas. Cats: ceruminous gland adenomas and carcinomas, sebaceous gland adenomas and carcinomas, squamous cell carcinomas and papillomas. Ceruminous gland tumors are more likely to be malignant in the cat (50% being ceruminous gland adenocarcinomas).

7. Systemic Diseases a. pyrexia - increased temperature, humidity in ears. b. immunocompromising disorders (FeLV, FIV, canine parvovirus,

canine distemper, severe debilitation, negative catabolic states)

*PERPETUATING FACTORS These are factors that are capable of perpetuating the otitis even if the primary factor has been removed/resolved:

1. Bacteria - bacteria most commonly associated with otitis externa: Staphylococcus intermedius, Pseudomonas aeruginosa, Beta hemolytic streptococci, Proteus sp., Enterococci, E. coli, Corynebacterium spp. Acute otitis externa is most commonly associated with Staphylococcus intermedius. As the otitis becomes more chronic or is chronically treated with topical antibiotics, gram negative bacteria tend to predominate with Pseudomonas aeruginosa being overrepresented.

2. Yeast (Malassezia pachydermatis) - part of the normal flora of the ear. Numbers may be slightly increased in dogs who are bathed frequently or have hair in their ears. In large numbers, Malassezia are capable of creating inflammatory changes (likely hypersensitivity to Malassezia by-products. Most common primary disease predisposing to Malasseszia proliferations is atopy.

3. Proliferative changes within the ear canals - most commonly caused by chronic inflammation. Anatomic changes associated with proliferative lesions produce a microenvironment that favors proliferation of bacteria and yeast. Proliferative changes frequently make successful topical treatment difficult. Chronic deep inflammation may predispose to calcification of the ear cartilages. This produces permanent anatomical changes which cannot be resolved with medical therapy (these are surgical candidates). The spaniel breeds (esp. the cocker spaniel) are renown for their rapid progression to this endpoint, no matter what the underlying cause for the otitis.

4. Otitis media - most commonly extension of otitis externa; can be caused by foreign bodies (grass awns); may be present in as many as 50% or more cases of chronic otitis externa.

5. Contact hypersensitivity/irritant dermatitis - most common offending agents - neomycin and propylene glycol. Ears may flare in the face of therapy or inflammation may just persist, often in spite of resolution of secondary infections. Tip off: finding of neutrophils in cytology where neutrophils were not present to begin with.

6. Treatment errors - overtreatment, undertreatment, inappropriate treatment. Overtreatment generally produces an ear that is too moist. On direct ophthalmaologic examination, the ear is often filled with whitish, opalescent material which, on cytologic examination are epithelial cells. These ears are also usually mildly inflamed. Reducing the frequency of medications (e.g. flushes etc.) will often quickly improve this problem.

PATHOGENESIS OF OTITIS MEDIA Inflammation within the middle ear (epitympanic recess, tympanic cavity and/or bulla) may be infectious (bacterial, fungal) or noninfectious (foreign body, neoplasia, polyps in cats, trauma, cholesteatoma).

Otitis media is most commonly an extension of otitis externa in the dog. In the

cat, while this is still the most common association, there appears to be a higher incidence on retrograde problems that involve the auditory canal. Obstruction of the auditory canal may result in the accumulation of mucoid secretions within the middle ear. Otherwise normal microflora of the middle ear may then produce infection. This pathogenesis is also uncommon. Middle-ear involvement via hematogenous spread of infection is rare.

In the dog, it has been estimated that otitis media is present in 50% or more of the ears associated with chronic otitis externa. A higher incidence is noted in those ears in which the horizontal canal is stenotic and when inflammation/purulent exudation is severe (e.g. Pseudomonas infection). However, especially in chronic allergic otitis externa, it would appear that perforation of the tympanum is much less common than the 50% quoted above. It is more common to see the tympanum partially forced in to the tympanic cavity and bulla (the so called "false middle ear) than it is to see actual perforation.

The bacteria associated with otitis media, in roughly decreasing order of occurrence include Staphylococcus intermedius, Malassezia pachydermatis, Pseudomonas spp., Corynebacterium spp., Enterococcus spp., Proteus spp., B-hemolytic streptococcus, alpha-hemolytic streptococcus, Citrobacter spp. E. Coli, and Anaerobes.

It is important to note that, with chronicity, the epithelial lining of the middle will potentially become markedly hyperplastic and may be responsible for much of the soft tissue density seen within the bulla on radiographic or CT/MRI examination. These changes may require prolonged times, with therapy, to regress.

Cholesteatoma are formed when the tympanum is pushed into the bulla by usually dry concretions. Epithelial debris continues to accumulate within this "pouch" until it fills the entire bulla. With time, pressure may be placed on the bulla wall to result in thinning of the bone and an actual expansion of the bulla.

Clinical Signs: In most cases, the signs of otitis media mimic those of otitis externa (pruritus, head shaking, pain, exudation). Neurologic signs are less commonly encountered (approx. 25% of cases). They include facial paresis and paralysis, Horners syndrome, KCS and xeromycteria (unilateral drying and hyperkeratosis of the planum nasale on the affected side). In that otitis media may extend to also involve the inner ear, other neurologic signs that may be present include e deafness, head tilt, asymmetric ataxia and horizontal nystagmus.

MANAGEMENT OF OTITIS EXTERNA IN THE DOG AND CAT EAR CLEANING

A clean ear must be achieved at some point in the work-up of every case of otitis externa: Debris serves as a potential source of irritation; may serve as a nidus of infections; may prevent the access of topical medications to their targeted area of need and may inactivate some of the ingredients in topical medications.

Ear Cleansers 1. "At home" flushing the ears on a once or twice a day basis to initiate

therapy (frequency depending on the severity of problem) is often sufficient to remove debris. Flushing is often started a few days after topical +/- systemic therapy for the otitis is initiated and the ear has been allowed to "quiet down". The author tends to use combination cleanser/dryers most commonly for this purpose (e.g. Epi-Otic; Virbac -

propylene glycol, dioctyl sodium sulfosuccinate, lactic acid, salicylic acid or Malacetic Otic; DermaPet Inc. - acetic acid, boric acid, surfactants and a drying agent). These products not only soften waxy debris, but also have a significant germicidal effect. Their value as adjunctive therapies in the management of otitis externa is supported by studies wherein they have been effective alone in managing otitis externa. In one study, an ear cleanser (Epi-Otic; Virbac) was used in 16 dogs with bacterial or yeast otitis externa. Twice daily flushing, done for two weeks, resolved the otitis in 83% of the dogs with Staphylococcus intermedius contributing to the otitis (12 ears), 100% of the ears with Pseudomonas (4 ears) and 72% of the ears with increased numbers of Malassezia (22 ears). Significant in vitro and in vivo anti-bacterial and anti-Malassezia effects of this product (Epi-Otic) and other "cleansers" have also been noted in treating otitis externa involving bacteria and/or Malassezia in the dog. Cleanser alternatives to be considered when debris is more refractory to removal would include:

2. Heavier oils for dry, more tenacious, waxy accumulations - Cerumene (squalane in an isopropyl myrisate liquid petrolatum base; Vetoquinol); messy to use. Fill the ear. Massage. Consider flushing out with dilute vinegar and water (1:2). Well tolerated if the tympanum is perforated (not ototoxic). Tends to keep the ear relatively moist between therapies; must monitor for over-treatment - keeping ear too moist.

3. For more tenacious, less dry debris - Otifoam (DVM; water, cocamidoprophyl betaniae, PEG 60, almond glyceride, mackalene 426, salicyclic acid, oil of eucalyptus) followed by OtiRinse (DVM; water, propylene glycol, DSS, glycerin, nonoxynol 12, salicylic acid, lactic acid, benzoic acid, aloe vera). This combination used no more frequently then once daily; may cause irritation.

4. Acetic acid (white vinegar; 5 % acetic acid). Diluted 1:1 to 1:3 in water. May be irritating in more concentrated solutions especially in more inflamed or ulcerated ears. Tend to start with a 1:2 dilution. Reasonably good germicidal actiivity (bacteria and yeast); unique anti-pseudomonal effects and is one of the flushes of choice when documented perforation of tympanum or suggestion of perforation (safe in middle ears;flush of choice when presented with an otitis media).

Techniques of Ear Cleaning 1. "At home" flushing: fill ear; massage in ; can place a cotton ball in ear once

it is full to facilitate keeping flush in ear and to "wick up" debris following massage. Allow pet to shake cleanser out.

2. Ear bulb syringe - ideally place ceruminolytic in ears 15 - 20 minutes before flushing (helps to soften material). Will generally flush ears, then allow dog/cat to shake head) if reluctant to do so, place on floor; will often shake here when will not do so on the table) then examine with ototscope to see what sort of job you have done.

3. AuriFlush (Shering) - allows for both flushing and suctioning, even in awake dogs and some cats. Does a reasonable job of removing debris from the canals but does not do well in removing debris from deep within the horizontal canal adjacent to the tympana.

Techniques for Ear Cleaning - Deep Ear Cleaning

In a predominantly referral practice, the author is commonly presented with cases of chronic otitis externa wherein the otitis is significantly perpetuated by a "wad" of debris (waxy concretion; ceruminolith) that has accumulated within the horizontal canal adjacent to the tympanum. The horizontal canal often becomes hyperplastic, narrowing the canal in this area. With chronicity, the tympanum is also commonly "pushed" in to the tympanic cavity to variable degrees. This scenario is most commonly encountered in cases of canine allergic otitis externa (atopy, food sensitivity) complicated by secondary Malassezia infections. A similar

situation is seen in cats, most commonly as a sequel to ear mite infestations or as a complication of allergic otitis. In cats, the horizontal canal epithelium is less likely to become hyperplastic and the tympanum is usually not significantly pushed in to the tympanic cavity as it is in the dog. The "at home" use of topical cleansers is usually not able to remove this debris. To resolve, or at least significantly improve the otitis, the debris must be removed. This is most effectively and a-traumatically achieved through deep ear cleaning under general anesthesia (flushing and suctioning through an operating otoscope or through a video-otoscope).

If, at presentation ears severely inflamed, usually elect to treat topically +/- systemically for several days to one to two weeks to reduce inflammation prior to more in- depth cleaning. For actual deep ear cleaning:

Once in to the ear, the author routinely uses an open ended tomcat catheter on a 12 cc syringe to obtain exudates from deep within the horizontal canal of the ear. Samples are used for cytologic examination and possibly culture. If the middle ear is entered during the cleaning, samples are again obtained as soon as this occurs (for both cytology and culture).

For effective, safer deep ear cleaning, the author prefers flushing and the use of a suction apparatus. The suctioning is of paramount importance. Flush under direct visualization through surgical ototscope head with an open ended TomCat catheter attached to a 12 cc syringe. Ideally, suction through vacuum system (e.g. suction hose attached to a 14 guage, 5.5. inch teflon catheter (Abbott Hospital Incorporated, North Chicago, IL 60064, No. 4535-84). It is important that the operator be able to control the intensity of the vacuum used. Particular care must be taken to reduce suction when working on or around the tympanum while greater suction settings can be used to remove larger, more tenacious material away from the tympanum. The author routinely uses only saline to initiate cleaning. However, if debris appears to be quite tenacious, a ceruminolytic (e.g. EipOtic or Cerumene) can be used to facilitate cleaning.

An alternative to the use of suction would be a 3.5 to 5 Fr feeding tube attached to a syringe.

-Alligator forceps - to remove large particulate material.

-Ear curettes - for removing larger amounts of material in vertical and horizontal canal; concern for using adjacent to the tympanum.

If the tympanum is found to be perforated or is intentionally perforated, debris should be flushed out with copious amounts of saline. Visualization of the middle ear may be facilitated through the use of a 1.9 mm or 2.7 mm arthroscope.

Cleaning Through the Video-Otoscope

Video-Otoscope: procedures are usually begun with a thorough examination of the ear. A picture may be taken at the initiation of the cleaning to document before and after improvement. A sample of debris is aspirated from the depths of the ear for both cytolgic examination and possibly for culture and sensitivity testing. If the culture is not deemed necessary at the end of the procedure (i.e. in light of cytologic findings; assessment of integrity of the tympanum), it can simply be discarded. If the tympanum is noted to be perforated, then samples should always be taken from both the horizontal canal and the middle ear for both cytologic examination and culture and sensitivity testing. It has been noted that the organisms from horizontal canal and middle ear may differ and that the sensitivity patterns of the same organism may also differ from one area to the other. Samples taken from the middle ear should always be submitted for culture

(both aerobic and anaerobic) even if they do not show cytologic evidence of organisms.

The administration of saline through the working channel will facilitate expansion of the canals, further magnification of images, prevents fogging of the lens and lessens debris accumulation around the tip. The pressure of gravity flow is usually sufficient. Loosening and flushing of debris is often facilitated by this maneuver alone.

Flushing and suctioning can be done through the working channel utilizing a 16 gage, 5.5 Inch teflon catheter (Abbot Hospital Incorporated) or a 4 1/2 inch, open ended tomcat catheter. The channel can be used for passage of biopsy or grabbing forceps or an appropriately modified ear curette. Debris can be grasped and removed, masses can be biopsied or removed, cysts "popped" or removed and polyps removed in cats. When utilizing the Storz double port adapter, fluids may be administered while biopsy forceps or grabbers are simultaneously used (Fig ).

A home made flushing and suction apparatus may be created that allows for alternating flushing and suctioning action through one catheter in the operating port. A 16 guage, 5.5 inch teflon jugular catheter (Abbot Hospital Incorporated, North Chicago, IL 60064) or a 5.5 inch, open-ended tomcat catheter can be attached via an extension set to a three way stopcock. For flushing purposes, a 60 cc syringe is also attached to the stopcock. The hose from a suction apparatus is the attached to the remaining portal of the 3 way stopcock. The "trick" to the use of this apparatus is control of suction. Excessive suction, will result in collapse of the canal. Minimal amounts of suction should be used when working deep within the canal, adjacent to the tympanum. It is possible to perforate the tympanum when suction is excessive.

The more rapid removal of debris from the canals is often facilitated by utilizing a combination of cleaning techniques. Alligator forceps and ear curretts can be utilized through a conventional operating otoscope head to remove larger debris. Flushing, utilizing a 12 cc syringe attached to an open ended tomcat catheter, then suctioning through a 14 gage teflon catheter (Abbot Hospital Incorporated) attached to a suction hose and controlled suction apparatus can allow for rapid debris removal with quicker directional changes within the canal. One shortcoming of the video-otoscope is the fact that the exit point of the operating channel is fixed. Any instrumentation coming out of this channel is fixed in its range of motion. The camera tip must be manipulated to assure access to various areas. This can be cumbersome and time consuming.

ROUTINE TREATMENT OF ACUTE AND INFREQUENTLY RECURRENT OTITIS EXTERNA

In many cases seen in clinical practice, such cases are often readily managed with topical products that contain a combination of an antibiotic, anti-fungal and glucocorticoid. The neomycin in products such as Tresaderm and Panalog provide reasonable gram positive and gram negative coverage; the thiabendazole in Tresaderm and the nystatin in Panalog provide reasonable anti-Malassezia therapy; and the dexamethasone in Tresaderm and triamcinolone acetonide in Panalog provide a relatively potent anti-inflammatory effect. When rods predominate in our Diff-Quick stained cytology, we often reach for the gentamicin in Otomax or if large numbers of Malassezia are noted, we may look for the superior antifungal effect of clotrimazole in Otomax. The betamethasone in an ointment base (Otomax) also appears to give us a more potent anti-inflammatory effect.

Systemic Antibiotics

Recommended when bacteria are seen on cytologic examination or culture and sensitivity testing and the problem is chronic and proliferative or when the otitis is severe and inflammatory changes are seen on cytologic examination (i.e. large numbers of neutrophils) or when there is a significant peri-aural dermatitis or if the tympanic membrane is perforated. Antibiotics are best chosen by culture and sensitivity testing but empiric choices include first generation cephalosporins when cocci are seen cytologically (e.g. cephalexin, cefadroxil) or enrofloxacin or marbofloxacin if rods are seen cytologically.

Systemic Glucocorticoids

Systemic glucocorticoids are an invaluable adjunctive therapy used to quickly reduce inflammation associated with more severe otitis externa (especially if allergic in origin). They are also the most effective therapy for reducing proliferative change secondary to inflammation within the ears. Generally start therapy with oral prednisone/prednisolone at .5 to 1.0 mg/kg/day (use higher range for more severe inflammatory changes).

Systemic Antifungals

Oral ketoconazole or itraconazole are generally excellent choices for treating more refractory Malassezia infections - especially where the owners are unable to do as good a job as we would desire for topical treatment or if the ears are quite proliferative and it is questionable as to what topical treatments alone will achieve. These drugs are also indicated for cases of otitis media wherein Malassezia are involved.

Client Education and Follow-up

It is very important to provide the client with instructions (medication application technique, frequencies, amounts etc.). The use of a "take home" instruction sheet may also be of value. For difficult to medicate dogs or cats, the owner may try placing the appropriate number of drops for a given treatment in a syringe (e.g. tuberculin) then rapidly squirting this in the ear.

Follow-up: the initial recheck for most cases of otitis externa is usually done two weeks after initiating therapy. Subsequent rechecks are dictated by response to therapy. Each follow-up examination should involve an otoscopic examination, cytologic examination of exudates and an accurate recording of findings. Routine rechecks should be maintained until the problem is either resolved or controlled.

ALLERGIC OTITIS EXTERNA Routine Treatment of Acute and Infrequently Recurrent Allergic Otitis Externa

In many cases seen in clinical practice, such cases are often readily managed with topical products that contain a combination of an antibiotic, anti-fungal and glucocorticoid. The neomycin in products such as Tresaderm and Panalog provide reasonable gram positive and gram negative coverage; the thiabendazole in Tresaderm and the nystatin in Panalog provide reasonable anti-Malassezia therapy; and the dexamethasone in Tresaderm and triamcinolone acetonide in Panalog provide a relatively potent anti-inflammatory effect. When rods predominate in our Diff-Quick stained cytology, we often reach for the gentamicin in Otomax or if large numbers of Malassezia are noted, we may look for the superior antifungal effect of clotrimazole in Otomax. The betamethasone in an ointment base (Otomax) also appears to give us a more potent anti-inflammatory effect.

Long Term Management of Allergic Otitis Externa 1. Resolve secondary bacterial/yeast infections with a broad spectrum

product such as Otomax (Schering), Panalog (Ft. Dodge), Tesaderm (Merial) etc.

2. Consider long term maintenance therapy with a topical glucocorticoid product devoid of an antibiotic.

a. More severely inflamed ears - Synotic (Ft. Dodge; fluocinolone acetonide and DMSO) once every 48 to 72 hours maintenance. Because this is a very potent steroid there is a concern for creating iatrogenic Cushingoid signs with more frequent, long term therapy. Dileterious local effects may also be seen within the ear (cutaneous atrophy).

b. Less severely inflamed ears - e.g. Bur-Otic HC (Virbac; propylene glycol, water, Burrow's solution, acetic acid, benzalkonium chloride); once every 48 -72 hours long term.

c. Many allergic patients are prone to recurrent Malassezia colonization/infections. Topical hydrocortisone is often not potent enough in these individuals to reduce their "flares" of allergic otitis. Improved control may be achieved with a mix of 1:2 or 1:1 dexamethasone sodium phosphate and 1% miconazole (Confite). The ratios are changed in accordance with the primary problem being managed within the ear (inflammation vs Malassezia). A common application protocol for this mix in a Golden retriever sized dog would be 0.5 cc twice weekly, as a long term maintenance regimen.

3. Combine these long term topical glucocorticoids with routine flushes using a combination cleanser/dryer 1-2 times per week.

4. Overall control of the otitis will be much easier if the patients underlying allergic problem is well controlled (e.g. hypoallergenic diet for food sensitivities or antihistamines, fatty acids, hyposensitization, glucocorticoids, cyclosporine etc. for atopy).

What to do with the Chronic, Proliferative Otitis Case 1. Aggressive attack at medical management - salvage the ear/ears. This

usually employs all the modalities of ear therapy commonly employed. a. Systemic glucocorticoid (e.g. starting at 1-2 mg/kg/day

prednisolone/prednisone for two weeks, then .05 - 1 mg/kg for two weeks, then 1 mg/kg every other day for two weeks, then 0.5 mg/kg every other day for two weeks). Systemic glucocorticoid therapy is generally maintained until proliferative changes have been significantly reduced or resolved.

b. Systemic antibiotic (chosen on the basis of cytology, +/- culture and sensitivity testing)

c. Topical glucocorticoid/antibiotic/antifungal d. Cleanser/dryer e. +/- systemic antifungal therapy f. Consider intralesional triamcinolone acetonide (2 mg/ml); spinal

needle (3.5", 22 gauge); injected following cleaning; 0.1 ml injections into proliferative lesions or if 360 degree proliferation, in "ring" of 3 points around wall, with each "ring" 1-2 cm apart.

Once the ears have been somewhat quieted down, an in depth cleaning/examination is in order.

Once secondary bacterial infections have been controlled and proliferative changes have been significantly improved, then potential primary factors can be further worked up and treated (e.g. document and treat food sensitivity; atopy management etc.).

Note: As part of our aggressive initial management of those chronic/proliferative ears - we will often start a restrictive diet at the outset of topical/systemic otic therapy. We prefer a commercial, balanced restrictive diet because it will likely be fed long term (several months) before a more definitive decision can be made about the actual role dietary hypersensitivity may be playing in the pathogenesis of the disease. Once more intensive topical/systemic therapy is completed and the ears doing well, see if diet alone is able to keep the otitis from recurring. To prove the benefit of restrictive diet, challenge with the previous diet to see if problem exacerbated and to document the future need of feeding special diets.

APPARENTLY REFRACTORY MALASSEZIA ASSOCIATED WITH OTITIS EXTERNA

True refractory infections with Malassezia appear to be uncommon. Recurrent infections, however, are frequently encountered (i.e. secondary to atopy). When Malassezia appears to be refractory, factors that may affect the efficacy of conventional therapies include:

1. Significant debris within the ear (see above) that may serve as a nidus for continued infection.

2. Hyperplastic changes that prevent access of topical medications to their target areas.

3. Inadequate control of underlying inflammatory disease (primary factors, especially atopy or food sensitivity). Management of these factors to maximize response usually requires glucocorticoid therapy (may require aggressive glucocorticoid therapy).

4. Some individuals appear to be sensitive to even small numbers of Malassezia, most likely due to the development of hypersensitivity to Malassezia and/or its byproducts. These individuals may require more aggressive, longer term therapy to adequately resolve their Malassezia.

Therapeutic considerations for the above situations include: 1. Thorough ear cleaning. 2. More aggressive work-up and management of underlying primary factors

(e.g. atopy, food sensitivity). 3. More aggressive topical and oral glucocorticoid therapy to reduce

inflammation and proliferative changes, producing a microenvironment that is less conducive to Malassezia colonization.

4. For Malassezia problems that appear to be slow to respond to apparently appropriate topical therapy (e.g. nystatin in Panalog, thiabendazole in Tresaderm), alternative therapies to consider are listed below. In making these recommendations, it should be noted that the author ranks the anti-fungal efficacy of these drugs (based on clinical impression; most potent to least) much as has been reported in one study : ketoconazole, clotrimazole, miconazole and nystatin 4.

a. Otomax (Schering Animal Health; clotrimazole along with a more potent glucocorticoid betamethasone).

b. Conofite lotion (Schering; 1% miconazole; use every 12 hr; Conofite may prove irritating in some ears; may add an anti-inflammatory component by utilizing a 1:2 mix of dexamethasone sodium phosphate and 1% miconazole, but dilution may affect efficacy.

c. Lotrimin AF (lotion; 1% clotrimazole with benzoyl alcohol, cetearyl alcohol; OTC; Schering); can also get 1% clotrimazole in PEG (Lotrimin AF solution; also other sources) but this is a messy product to use because of the PEG.

d. Ketoconazole powder (Medisca; 1-800-932-1039) - 2% solution made up by mixing 200 mg ketoconazole in 5 cc PEG and 5 cc ethyl alcohol.

e. Oral ketoconazole; 5 - 10 mg/kg q 12 to 24 hours for 2-4 weeks. In the author's experience, BID therapy has been more effective in

refractory cases. Oral itraconazole (5 - 10 mg/kg/day for 2-4 weeks or longer).

REFRACTORY BACTERIAL INFECTIONS (emphasis on Pseudomonas)

Resistance is suspected if: 1. Bacteria persist in the face of appropriate "first line" topical therapies (e.g.

Tresaderm, Panalog) 2. Otitis externa has received frequent, periodic therapies with "first line"

products 3. Large numbers of rods are seen on cytologic examination (suggesting the

possibility of more resistant gram negative organisms such as Pseudomonas).

Examples: Gentocin-Otic (gentamicin, betamethasone ) or Otomax (gentamicin, betamethasone, clotrimazole). If these products fail to resolve the bacterial component of the problem, then further treatment is dictated by culture and sensitivity testing (usually stop the gentamicin containing product for 3-5 days prior to culturing).

Current options for managing resistant Pseudomonas infections

Pseudomonas infections are quite commonly encountered as complicating factors in chronic otitis externa/media in the dog and, on occasion, may be very resistant to routine anti-microbial therapy. The following are important points to consider in establishing a successful therapeutic protocol for such cases:

1. The presence of a Pseudomonas infection is usually heralded by the presence of purulent exudate within the ear. Cytologic examination will reveal "rods" and usually neutrophils on cytologic examination with Diff QuickR or new methylene blue stained slides.

2. Pseudomonas infections are more likely to be associated with breakdown of the tympanum and the concurrent presence of otitis media. Otitis media is even more common if the canals are hyperplastic and stenotic. These associations warrant early consideration of a thorough "deep" cleaning, direct visualization of the tympanum (when possible) and/or radiographs, CT scanning or MRI to better evaluate for the presence and severity of middle ear involvement.

3. Affected ears are often very inflamed, swollen and painful and may be eroded or ulcerated. Most patients have underlying primary factors (e.g. allergy) responsible for initiating the otitis. Proliferative changes are often present as perpetuators. As such, significant benefit is obtained from concurrent oral glucocorticoid therapy (oral prednisone/prednisolone starting at 1 - 2 mg/kg/day; dose dictated by the severity of inflammation and the degree of proliferative changes).

4. With more acute, first time occurrences, the empiric antibiotic we tend to reach for when "rods" predominate on cytologic examination is gentamicin (i.e. Otomax, Gentocin Otic;Schering) BID. This antibiotic does pick up a significant number of Pseudomonas strains (50 - 60%) and also works well against other gram negative organisms. Preferential flushes to be used twice daily prior to the use of this product would be a Tris-EDTA containing product (e.g. T8 solution, DVM; Triz-EDTA, DermaPet) or an acetic acid containing product (e.g. Malacetic Otic, DermaPet Inc. or dilute white vinegar and water - 1:2). Failure to respond to this therapy would warrant culturing the ear. Should the tympanum be perforated or the integrity of the tympanum is unknown, alternatives to gentamicin should be considered (concern for ototoxicity).

5. Chronic cases, especially with histories of unsuccessful topical antibiotic treatments, are cultured prior to the initiation of topical therapy (samples for cultures should be taken from both the canals and, if involved, the

middle ear in that bacterial species and strains may differ from one to the other).

6. Other antibiotics available for topical use based on culture and sensitivity testing or while awaiting C and S data include:

a. Enrofloxacin in conjunction with Tris-EDTA. Pseudomonas resistance to enrofloxacin is quite commonly encountered. However enrofloxacin is a well tolerated drug whose potential for ototoxicity appears to be minimal. When used in conjunction with tris-EDTA, its in vitro efficacy appears to increase dramatically. Tris-EDTA has the ability to increase the susceptibility of various bacteria to several antibiotics. In one study, refractory otitis was associated with strains of Pseudomonas aeruginosa, Staphylococcus aureus, E.coli and Proteus mirablis that were all resistant to enrofloxacin, cephaloridine, or kanamycin. All cases were resolved with the same antibiotics following BID pre-treatment of the ears with Tris-EDTA7. It has also been suggested that Tris-EDTA may also have inherent antibacterial and anti-Malassezia effects. There are currently two Veterinary Tris-EDTA products on the market. T8 solution (DVM Pharmaceuticals) also contains additives which impart some inherent cleaning potential for the product. There is some question about its increased potential for ototoxicity because of these additives. TrizEDTA (DermaPet Inc.) does not contain these additives. When using these products in combination (tris-EDTA and enrofloxacin), the author tries to achieve a final concentration of 10 mg/ml of enrofloxacin (i.e. 13 mls of 100 mg/ml injectable enrofloxacin per 118 ml bottle of T8 solution). Others have claimed similar success with concentrations of 4 - 5 mg/ml of enrofloxacin.

b. Baytril Otic (Bayer; 5 mg/ml enrofloxacin, 10 mg/ml sliver sulfadiazine). Silver sulfadiazine is also effective against a broad spectrum of gram positive and negative bacteria, including Pseudomonas. In addition, it is a mildly effective therapy for Malassezia. In ears that have only bacterial infections, silver sulfadiazine helps to reduce the incidence of opportunistic Malassezia infections that may develop when the ears that are treated with topical antibiotics alone. This product can be used with a pre-treatment of Tris-EDTA (see above).

c. Other enrofloxacin mixes utilizing injectable (22.7 mg/ml) enrofloxacin include:

i. 1:2 (saline to enrofloxacin), 1:1 enrofloxacin - BID ii. 3-4 cc enrofloxacin to 8 cc Synotic BID (for potent steroid

effect) iii. 1:2 or 1:1 enrofloxacin: dexamethasone sodium phosphate

(for moderate steroid effect) iv. 1 part enrofloxacin to 1 part Dexamethasone phosphate to 2

parts 1% miconazole (Conofite) (for concurrent anti-Malassezia effect)

d. Polymixin B containing products have been shown to be very efficacious based on in vitro sensitivity testing (variably reported as 95%-100% sensitive in the USA, where polymxin B is not used in routine ear preparations). Examples: Cortisporin Otic solution, Glaxo Wellcome - polymixin B, neomycin, 1% hydrocortisone; Colymycin S. Otic , Parke-Davis - colistin or Polymixin E, neomycin, 1% hydrocortisone. Contraindicated if a perforated tympanum.

e. Ticarcillin or Ticarcillin and clavulonic acid (Timentin; GlaxoSmithKline). Ticarcillin hs proven to be a very beneficial therapy for resistant Pseudomonas in the author's experience. The author uses Timentin as 3.1 gm vial; reconstitute with 26 ml (100 mg/ml); freeze in 2 ml aliquots; thaw and use each 2 ml aliquot over 2 days; 1/2 ml in each ear BID. Others have suggested:

reconstitute a 6 gram vial of ticarcillin with 12 ml of sterile water. Divide equally into 2-ml portions in syringes and freeze (will remain stable for 3 months); this is the "stock solution". To make up the ear treatment solution, thaw and mix a 2 ml aliquot of concentrate with 40 ml of normal saline. Divide this into four 10-ml aliquots and freeze. Clients should keep these frozen; one aliquot should be thawed at a time, keeping it refrigerated, and used for no longer than 1 week. Anything remaining after 1 week should be discarded and another aliquot thawed.

f. Silver sulfadiazine - very efficacious therapy (although the author has seen resistant cases) - SilvadeneR cream (diluted 1:9 with water) or powder (Spectrum pharmacy; www.spectrumRx.com; make up 1% solution). Ear should be cleaned prior to application to enhance efficacy. May promote re-epithelialization in ulcerated ears.

g. Amikacin injectable (dilute 250 mg/ml to 50 mg/ml) 4-8 drops of 50 mg/ml BID

7. We do routinely recommend flushing affected ears. This can be achieved with the Tris-EDTA solutions noted above. Alternatively, because of their unique anti-pseudomonal effects, acetic acid flushes (i.e. acetic acid 5% - white vinegar- diluted 1:2; Malacetic Otic (DVM) - 2% acetic acid, 2% boric acid) can also be used. We generally flush the ears once or twice daily.

8. Systemic antibiotic therapy - There is some evidence supporting the efficacy of systemic antibiotic therapy alone in treating bacterial otitis (improving 43% or resolving 28% of cases in one study)8. Our indications for the use of a systemic antibiotic: canals are hyperplastic or proliferative, erosive or ulcerated and/or there is otitis media or it is difficult for the owners to topically treat the ears. However, it is important to note that the author has treated many cases of Pseudomonas otitis externa +/- media with just a topical antibiotic (e.g. Tris-EDTA and enrofloxacin or ticarcillin and acetic acid flushes) alone. The author's antibiotic of choice is marbofloxacin (2.5 - 5.5 mg/kg/day; current therapy of choice); alternatives are enrofloxacin (10 - 20 mg/kg/day), or ciprofloxacin 15 - 20 mg/kg/day. Appropriate antibiotics are generally chosen on the basis of culture and sensitivity testing. When asking for sensitivity data on suspected cases of Pseudomonas infections, one should ask for sensitivities to enrofloxacin, ciprofloxacin, marbofloxacin, ticarcillin and ceftazidime, in addition to those routinely performed. Most laboratories will provide sensitivity data based on the Kirby Bauer disc system. When looking specifically at enrofloxacin, the author uses the following guidelines in interpreting sensitivity data. If the organism is sensitive, then the lower dosage of fluroquinolone can be used. If resistance is noted on the KB system, then MIC's should be requested. If the MIC is between 2-4 micrograms /ml, then the higher dosages of antibiotic should be used. If the MIC is above 4 micrograms/ml, then the bacteria should be considered resistant to enrofloxacin. Alternative systemic antibiotic considerations for very resistant Pseudomonas would include ticarcillin or ceftazidime (ticarcillin, 60 - 75 mg/kg BID SubQ or ceftazidime 30 - 50 mg/kg BID SubQ) for 2-3 weeks. These injections can be given at home by the owner.

9. Because of the relatively high incidence of underlying allergies that predispose to Pseudomonas infections, the author routinely starts a work-up and therapy for these problems as soon as possible (e.g. start restrictive diet to rule out food sensitivity).

*OTOTOXICITY

The use of topical medications in an ear with a perforated tympanum must be approached with caution. Absorption into the inner ear is through the round or oval window; the round window may become more permeable to macromolecules

in the presence of otitis externa.

Antibiotics with the potential for ototoxicity include the aminoglycosides (amikacin, gentamicin, kanamycin, neomycin), erythromycin, polymixin B and E, hygromycin and chloramphenicol. The author is not aware of ototoxicity associated with the use of enrofloxacin or ticarcillin.

Ototoxicity has also been noted in association with propylene glycol (a very common ingredient in most topical otic preparations) and other ingredients commonly used in various ceruminolytic preparations.

Aminoglycoside (amikacin, gentamicin, kanamycin, neomycin) toxicity is noted to be predisposed to by length of administration, dose, the presence of pre-existing sensorineural hearing loss or vestibular function, health status of the patient, concurrent use of potentially ototoxic drugs, renal impairment and genetic predispositions. There is anecdotal suggestion that ototoxicity may also be potentiated by general anesthesia.

It is important to note that much of the above data regarding antibiotic ototoxicity has been generated in rodent studies, using concentrations of antibiotic that are far in excess of those used in commercial preparations. In dogs and cats, the incidence of ototoxicity associated with these antibiotics appears low. In one study, the topical administration of 0.3% gentamicin twice daily for 21 days in dogs with experimentally ruptured tympanic membranes failed to bring about any clinical vestibular or BAEP changes. Similar studies over similar periods of time failed to show ototoxicity associated with chlorhexidine..

The use of these drugs should be considered if indicated by clinical, cytologic and culture and sensitivity data.

Note: Cats appear to more sensitive to the ototoxic effects of these drugs than are dog.

Products that are considered to be safe for topical use in the face of a perforated tympanum:

1. Antibiotics - enrofloxcin, ticarcillin 2. Steroids - dexamethasone sodium phoshate (injectable); Synotic

(fluocinolone and DMSO)? 3. Flushing agents: acetic acid and water (1:2); DermaPet Ear Wash (2%

acetic acid, 2% boric acid); squalene (Cerumen, EVSCO), Triz EDTA (DermaPet).

© 2005 - Rod A. W. Rosychuk, DVM, DACVIM - All rights reserved