The Itchy Dog Part I: Infection/Parasites/Work Up

Charlie C Pye DVM, DVSc, DACVD

Assistant Professor, Atlantic Veterinary College, Charlottetown, PEI

Overview of the Issue

Ah the good old “itchy dog” appointment…..a frequent entry into your daily schedule during the week. These dermatology cases can be frustrating as multiple dermatologic diseases can present very similarly, meaning a number of diagnostic tests must be run prior to a final diagnosis. Many clients coming in with their pet specifically want that “magical pill” to fix the problem so it is important to discuss with them the long term plan and how we will arrive at that final diagnosis and decide upon treatment. In today’s lecture we will start with the work up for an itchy dog; how to rule in/out infection and parasites. In the second part of the lecture, we will review the work up for an itchy dog with allergic skin disease.

The Threshold Theory of Pruritus

This theory suggests that individuals can tolerate a certain level of stimulus and discomfort before they will exhibit clinical signs of pruritus. If patients are below this “level” they will not show any signs of being pruritic. Once above this level is when owners will report biting, chewing, licking, scratching and other signs that their pet is itchy. The goal with any dermatologic disease is to try and bring the patient below this threshold so they are comfortable and non pruritic; we can achieve this by dealing with as many parts of the equation as possible e.g. in an allergic patient who also has a bacterial pyoderma, we would treat the pyoderma but also address the underlying allergy at the same time.

Set Yourself up for Success

Owner frustration generally arises due to unrealistic expectations. To set yourself up for success, it is best to explain to owners that skin disease can be a long road and that multiple tests might be needed before arriving at that final diagnosis. Although this may seem overwhelming to owners to begin with, it will be less frustrating for them long term as opposed to just repeated visits that they were not expecting and ups and down in their pet’s clinical response. I also take time to explain to owners that their pet could be on multiple treatments to begin with so therapy can be somewhat “aggressive” at the start, but the goal is to have their dog on as few treatments as possible long term. I also stress to owners that my aim is not to have their dog “never scratch again”…everyone scratches here and there! A dog who never scratches is over-medicated and the situation should be reassessed. I try to discuss with owners what they are able to do with their pet before recommending treatments e.g. will the dog tolerate bathing? Can they administer injections? Can they give pills? If owners are unable to perform a treatment, it will not be successful at controlling their pet’s pruritus. For diseases that cannot be cured such as allergic skin disease, endocrinopathy etc, I emphasize that we are not aiming for a CURE but rather to MANAGE the disease aka “this means your dog

will be on a certain treatment for the rest of his life”. This is one of the first things I will say to clients in these cases so their expectation will not be that the medication can be stopped after 2 months.

Key Diagnostic Steps for the Itchy Dog:

1. Signalment

Signalment of your patient can provide some important information that can aid in creating your differential diagnosis list. For example, an intact male dog could have developed symmetric alopecia due to a sertoli cell tumour and an 8 month old pruritic dog is unlikely to have developed cutaneous neoplasia or an endocrine disease. There are breed predispositions for many dermatologic diseases - a full list can be found on the CIDD database through the University of Prince Edward Island.

2. History

Obtaining a thorough history is, for me, the most important part of a dermatologic work-up. By asking the correct questions, you can usually create a fairly good differential diagnosis list from the history alone. Often time constraints in general practice will prevent a thorough history taking. Derm questionnaires can be used to obtain all the information you need from your clients. These can be sent to clients ahead of time, filled in and brought to the appointment. Alternatively you can ask “Derm” clients to come to their appointment ten minutes early to fill in a questionnaire right before the appointment. We also ask our clients to bring previous medications and a picture of the current diet to their appointments so we have all the information (and are not left with the standard “what food is Fluffy on?”…”Oh the blue bag”). Another option for Derm appointments would be to have technicians go in and take a thorough history which they can then come and report to you without all the added information that clients often throw in. Booking slightly longer appointments for Derm cases can also be helpful. If diagnostic testing needs to be performed, drop-offs can also be scheduled so the patient will be in clinic all day and testing can be done when time permits.

Examples of questions to ask during a derm history taking include: A) Is your pet itchy?

• Also need to ask if they lick, bite, chew, rub on furniture etc as some clients will say their pet is not itchy as they do not see them scratch with their feet, but when asked if the dog licks they will report excessive licking

B) How itchy is your pet on a scale of 1-10?

• The Canadian Academy of Veterinary Dermatology has an Itch Scale for this purpose

C) Are other animals/humans in the house affected?

• Always a good idea to start with “You don’t have to show me but…”

• If other individuals are symptomatic this will increase your suspicion of a contagious or zoonotic disease

D) How did he respond to previous medications?

• If the pruritus resolves with glucocorticoid treatment, this could be indicative of an environmental based allergy

• If pruritus does not resolve with glucocorticoid therapy you could be dealing with a case of food allergy, Sarcoptes, cutaneous lymphoma etc

• If pruritus resolves completely on antibiotics and doesn’t return for a while, the underlying etiology is more likely to be an endocrine disorder - endocrine disorders are generally non pruritic diseases but can become pruritic if a secondary infection is present

E) Did the itching get worse after a treatment?

• If the answer is yes, you could be dealing with a cutaneous adverse drug reaction F) Which areas of the body are affected?

• Certain diseases will target specific regions of the body; for example, a stereotypical Sarcoptes patient will demonstrate crusting of the lateral ear margins, crusting of the hocks and elbows and often a papular eruption on the ventrum along with intense pruritus

• Diseases should not be discounted as a potential diagnosis if the presentation is not stereotypical

G) What age did the issue start?

• Individuals presenting with derm disease at a young age are more likely to be diagnosed with an ectoparasite or a food allergy versus older individuals who might have an endocrinopathy or neoplasia

H) Are there any other signs of systemic disease?

• Pets with food allergies may also exhibit gastrointestinal signs such as chronic diarrhea

• Pets with hypothyroidism may show the classical signs of weight gain and lethargy I) Is there any seasonality to the skin problems?

• An individual who is only pruritic during the summer months is more likely to have a seasonal parasite or atopic dermatitis

• An individual who is pruritic year round could have an underlying food allergy or atopic dermatitis (in this case they may be reacting to dust mites or mould spores that are present year round)

3. Physical and Dermatologic examination

A dermatology examination should include all regions of the body. When doing my dermatologic examination I always start nose to tail along the back, then go down each leg in turn (flipping the paws over as I go) and then check along the ventrum. Even if the owner comes in for an ear infection (for the fifth time in the last year), by looking at the rest of the dog you might find they have interdigital erythema as well as a mild rash on their ventral abdomen. Upon questioning (back to how important history taking is), the

owner might then state “oh yes she chews at her feet and licks her belly as well”. This could indicate that the dog has atopic dermatitis leading to the recurrent otitis. Without examining the rest of the animal and probing with more questions, you might not have had access to this important information.

Certain areas of the body are affected more with certain diseases so having this thorough exam gives you even more information to help you determine which diagnostic tests are appropriate. Favrot et al came up with criteria to aid in determining the likelihood of atopic dermatitis (CAD) in the dog. They suggested that fulfillment of 5 of these criteria met with a high sensitivity and specificity:

1. Age at onset <3 years

2. Mostly indoor 3. Corticosteroid-responsive pruritus

4. Chronic or recurrent yeast infections

5. Affected front feet 6. Affected ear pinnae

7. Non-affected ear margins

8. Non-affected dorso-lumbar area

Using just these criteria you will still “miss” up to 1/5 dogs that have atopic dermatitis.

After a thorough examination and history taking - a differential diagnosis list should be formed to then select the appropriate diagnostic tests to perform. The following diagnostic tests are one which can be used to “work up” a pruritic dog.

4. Flea Combing

Useful to check for the presence of fleas. Comb onto a wet paper towel, pat towel together. If there is a colour change to red this indicates the presence of flea dirt on the individual.

5. Skin Scrapings +/- Parasiticidal trial

Skin scrapings are used to check for ectoparasites such as Demodex, Sarcoptes, Cheyletiella etc. Deep skin scrapings are useful to identify Demodex mites. Superficial skin scrapings are used to identify Sarcoptes mites and Cheyletiella. Use a dull scalpel blade and scrape in the direction of the hair growth, at a 45 degree angle, using the flat portion of the blade, after mineral oil application. For deep scrapings it is important to squeeze the skin between scrapings and scrape until there is some capillary oozing. Then put the sample onto a slide and examine under the microscope. When examining it is important to turn your light source down and you condenser down. Sarcoptic mites can be difficult to find on superficial skin scrapings. In cases where Sarcoptes is highly suspected but mites cannot be identified, a parasiticidal trial would be warranted.

6. Cytology

Ear cytology and skin cytology can be performed with a Q tip and then rolled onto a slide. Cytology samples can be heat fixed and then stained using Diff-Quik® and viewed under the microscope. Acetate tape preparations can also be used for dry lesions or if a yeast dermatitis is suspected. Clear acetate tape should be used for these sample. A small piece of tape is taken and then “stuck” onto the lesion multiple times. The tape is then stained using Diff-Quik® (but NO fixative), put onto a slide and examined under the microscope. Impression smears are another way to obtain samples and can be particularly useful for very exudative lesions or for taking samples under crusts.

There is increased adherence by S. pseudintermedius to corneocytes of canines with atopic dermatitis therefore all allergic patients should have cytology performed to determine if a bacterial pyoderma or a yeast dermatitis is present.

Cytology can also be helpful to search for the presence of inflammatory cells such as neutrophils or for abnormal cells such as acantholytic cells that could indicate the patient may have pemphigus foliaceus.

7. Bacterial culture and sensitivity (aerobic)

Antibiotic resistance is a growing concern in veterinary medicine. More and more patients are being diagnosed with resistant bacterial strains and needing a change in their antibiotic protocol. If a patient is non responsive to appropriate antimicrobial therapy prescribed for an appropriate period of time and bacteria are still found on skin cytology, you may be dealing with a resistant bacterial strain. In these cases an aerobic bacterial culture and sensitivity should be performed. Using a sterile culture swab, the affected areas are swabbed and then the sample sent to a lab for speciation and susceptibility testing.

8. Wood’s lamp and Fungal Culture

The Wood’s lamp is a good screening tool for cases of dermatophytosis due to Microsporum canis. Only 50% of Microsporum canis cases will fluoresce under the lamp so this is not a definitive diagnostic test for dermatophytosis. The wavelength of light needed for the fluorescence to occur is temperature dependent so the lamp needs to be able to warm up for at least ten minutes before use. In any derm case it is a good idea to turn the lamp on prior to the patient coming in, in case the lamp is needed. The lamp should be moved slowly over the animal so the hairs have a chance to fluoresce. True Microsporum canis infections will cause the hairs to fluoresce an apple green colour. There are lots of potential false positives due to other things that can fluoresce but these tend to fluoresce more of a yellow colour e.g. lint, certain topical medications, dander.

A fungal culture is the gold standard for diagnosing dermatophytosis. Cultures can be run in house or can be sent out to a lab - I generally recommend sending to a lab to prevent contamination within the hospital or misinterpretation of colour change of the medium. Labs will also be able to identify the species of dermatophyte under the

microscope. Culture samples can be obtained by collecting hair and skin from lesions, using either a scraping or plucking hairs from the edges of lesions. In asymptomatic individuals or individuals with few lesions, the Mackenzie toothbrush technique can also be used to obtain a sample.

5 KEY “TAKE HOME” POINTS:

1. With dermatologic cases, always set yourself up for success by discussing with the owner the need for diagnostic tests, the need for follow up and the likelihood that their pet may need long term therapy.

2. A thorough history is the most important part of any dermatologic examination.

3. Baseline diagnostic tests in any pruritic canine should include skin scrapings and cytology.

4. Bacterial culture and sensitivity should be performed in any individual you are suspicious may have a resistant bacterial infection (a patient who has been on an appropriate antibiotic for 4 weeks who still has lesions from a bacterial infection and bacteria on skin cytology).

5. Even non pruritic diseases can present as pruritic if a secondary infection is present - by identifying and addressing the infection we can then gather more information on the underlying disease process.

The Itchy Dog Part II: Allergies Charlie C Pye DVM, DVSc, DACVD Assistant Professor, Atlantic Veterinary College, Charlottetown, PEI Overview of the issue Once the possibility of a parasitic dermatitis has been ruled out and any secondary infections are being treated, we often rule in an allergic dermatitis as the cause of the pruritus in our patient. An allergic response is defined as a hypersensitive immune reaction to a substance that normally is harmless and would not cause an immune response. Food allergies, flea allergies and environmental allergies can cause allergic reactions in our patients. Flea allergic dermatitis is effectively treated using flea preventatives and anti inflammatory therapy for the patient’s comfort. For the purposes of this lecture we will focus more on food and environmental based allergies. Food Allergies The term “Food allergy” is often used incorrectly in veterinary medicine to describe any adverse reaction following food ingestion. The term “Food allergy” should be reserved for immunologic-based hypersensitivities. The American College of Veterinary Dermatology classifies any abnormal reaction after ingestion of food or additive as a Cutaneous Adverse Food Reaction (CAFR). CAFRs have been classified as follows:

1. Food hypersensitivities (immunologic adverse reactions)

a. Food allergies - IgE-mediated reactions or Type I hypersensitivity

b. Non-IgE mediated hypersensitivity - Type III and/or IV hypersensitivity

2. Food intolerance - non-immunologic adverse reactions

a. Food-dependent factors - toxins / poisoning or contaminants

b. Host-dependent factors - enzyme deficiencies, drug reactions, idiosyncrasies

The major food allergens are heat-stable, water-soluble glycoproteins of molecular weights between 10 to 70 kilodaltons. We know that peptides as small as 3 to 5 kd may be allergenic in dogs. Proteins greater than 70 kd are too large to be absorbed through intact enteric mucosa and therefore are not considered allergenic. Food allergies are the third most common allergic skin disease in dogs following flea allergic dermatitis (FAD) and atopic dermatitis (AD) and account for 32.7% of all allergic conditions.

Signalment

There is no sex predilection for CAFRs in dogs and cats. Multiple breeds are predisposed to the development of CAFRs including: Labrador retrievers, cocker, Soft-Coated Wheaton terrier, dalmatian, West-Highland white terrier, Bichon Frisee, collie, Shar Pei, Lhasa apso, Dachshund, miniature schnauzer, boxer, springer spaniel, Cairn Terrier, Irish / English setter, Golden retriever and German shepherd dogs. The age at presentation of dogs with a

CAFR is typically less than one year (2 months to 16 years; 33–52%); in fact one third to one half of dogs with CAFR develop clinical signs prior to one year of age. In general, an underlying CAFR should be considered in any pet that develops pruritus / clinical signs prior to 6 months and after 6 years of age, with no previous history of skin disease.

History

The most common clinical sign noted in a patient with a true food allergy is non-seasonal pruritus (unless different diets are being fed based on season!). The majority of dogs who develop a CAFR have been on a diet containing the offending allergen for years so it is uncommon to note clinical signs directly after a food change. This fact is one that owners find difficult to comprehend (How can he be allergic to his food, he’s been fine for years?). Pets can also be allergic to more than one antigen in a diet, including the preservatives - the mean number of food items a dog is allergic to is 2.4. Food allergic patients may respond temporarily to antimicrobial therapy as secondary infections are treated, but pruritus will then return at the end of therapy. Greater than 60% of patients with food allergies have a minimal to absent response to anti-inflammatory doses of glucocorticoids. Patients with atopic dermatitis often have a complete response, if secondary infections are not present. As previously discussed, history taking is important for any dermatologic case. If a patient is thought to have food allergies, the history taking should include further questions regarding previous diets fed, treats and table scraps given, flavoured medications such as monthly flea preventatives, flavoured toys/chews, pilling vehicles and flavoured toothpastes. Often these questions will need to be phrased multiple ways to receive the desired response. For example, “What do you feed your dog?” may be answered with “Diet X”. This answer doesn’t mean this is the only things the dog receives by mouth. It is best to also ask questions about what treats are given, any table scraps, anything used to give pills in. May clients will feel they have already done “diet trials” and ruled out food allergies by feeding a grain free diet - it should be emphasized that more criteria need to be fulfilled for a proper food trial to have taken place. Questions should also be asked in reference to any gastrointestinal disturbances; such as stool consistency, flatulence, number of bowel movements etc. Coprophagic dogs may obtain undigested material that could affect a food allergy.

Clinical Signs Cutaneous Findings The most common clinical sign of food allergy is pruritus, although not every patient will present with this sign (not all allergies itch). Erythema, scaling, crusting, alopecia, hyperpigmentation and papular eruptions are other common clinical signs, especially if secondary infections have been/are present. Urticaria and angioedema are less common but can occur. Malodor might be a client’s primary concern and can occur when a

secondary bacterial or Malassezia dermatitis is present. In dogs with CAFR, the ears are most consistently involved (80%) followed by the feet (61%) and the inguinal / perineal region (53%) (think ears, feet and rears). However, otitis, pedal pruritus and perianal pruritus can also be seen in cases of atopic dermatitis. In a recent study 51% of dogs with perianal pruritus had underlying food allergies but 49% had perianal pruritus due to atopic dermatitis. In 24% of dogs, the ear may be the only affected region of the body and otitis can be bilateral or unilateral. Axillary, anterior foreleg and periorbital regions were nearly equal in occurrence (31–37%). Many dogs will also have dorsal pruritus and if this pruritus extends past the thoracolumbar region, this will increase the suspicion of an CAFR in my opinion. Other cutaneous conditions that may be triggered by CAFR include Cocker Spaniel idiopathic seborrhea, symmetric lupoid onychodystrophy, sterile interdigital cysts, chin acne, pemphigus complex, perianal fistulas, pinnal vasculitis, recurrent generalized demodicosis, and food-induced cutaneous vasculitis.

Gastrointestinal (GI) Signs Up to 32% of patients with CAFR will present with concurrent gastrointestinal signs, as well as cutaneous signs. These include vomiting, changes in the stool consistency, increased frequency of bowel movements, halitosis, borborygmus, flatulence, tenesmus, eosinophilic or lymphocytic-plasmacytic colitis / IBD, anal gland impaction & scooting, pica and/or coprophagia. Other Related Signs Neurologic / behavioral signs such as malaise, seizures, behaviour changes, dominance aggression, attention deficit disorders and difficulty in training, have either been proposed, documented or are currently being researched. Respiratory signs associated with CAFR include asthma, rhinitis and sinusitis. Musculoskeletal conditions potentially attributable to food allergies include sterile polyarthritis and masticatory muscle myositis. Concurrent conditions noted with frequency include environmental, flea, intestinal parasite and insulin hypersensitivities, secondary recurrent pyoderma and Malassezia pachydermatis infection (may be the only sign).

Urinary signs such as eosinophilic urinary tract infections have also been documented to potentially be triggered by an AFR. Diagnosis Unfortunately, there is currently no gold standard diagnostic test to diagnose a food allergy other than performing a restricted diet trial using a novel protein or hydrolyzed protein. There is a lack of correlation between food allergy, RAST or ELISA results, gastroscopic

food sensitivity testing, colonoscopic allergen provocational studies (COLAP), salivary antibody testing and in vivo intradermal allergy test results. For many of these tests positive predictive values are often low and negative predictive values are often only approximately 50-60%. Patch testing for food allergies is currently being investigated as an alternative method to diagnose a food allergy. Dietary Restriction In a patient with a presumed food allergy or CAFR, a restricted diet trial should be recommended. When performing one of these trials there are many boxes that need to be “checked” to make sure the diet trial is being done correctly. 1. The diet should be changed to one with very limited ingredients - usually a single

protein and carbohydrate or a hydrolyzed protein source. 2. The diet selected should be one containing ingredients the individual has not been

exposed to previously (this is where obtaining a thorough dietary history, if possible, is important). Protein sources are more often to blame than grains for CAFR, so selecting a novel protein with no history of exposure is paramount. Food items most commonly causing food allergy include beef, dairy, wheat, chicken - I would also add lamb and corn to that list.

3. The diet trial should take place over an 8 week period and during that time the diet must be completely restricted with no treats, scraps, pilling vehicles, flavoured chews, flavoured medications etc given. **Treats can be given if the ingredients are identical to those in the diet e.g. on a kangaroo diet could get kangaroo treats**

To emphasize point number 3, I tend to tell clients that all that can go into their pet’s mouth for the next 8 weeks is this kibble, this canned food (if available), these treats (if available), water and pills! I also explain to clients that “a little goes a long way” when it comes to food allergies and CAFR. Studies have shown that a flavoured monthly flea preventative, if given to an individual allergic to the flavouring, can trigger an allergic reaction for 4 weeks. When selecting the ingredients in the new restricted diet, I also take the following into account:

• 50% of people allergic to one type of fish are allergic to another

• Some people allergic to chicken are also allergic to eggs and there may be an increased risk of allergy to other bird meats such as turkey, duck, pheasant

• 10% of human patients allergic to milk are also allergic to beef

• There is a protein in venison that cross reacts with a protein in beef

• Individuals with environmental allergies can have Oral Allergy Syndrome and symptoms can be exacerbated if they eat fruits and vegetables that cross react with pollens they are allergic to

The gold standard of performing a restricted diet trial is to use a home-prepared diet as

this also removes the potential that the dog could be reacting to preservatives within the diet. The preferred diet should include a novel protein source and a carbohydrate. These diets do need to be balanced for long term feeding. Restricted raw food diets may also provide some benefit to dogs with CAFR although concerns re bacterial contamination/overgrowth should be identified and discussed with the owners. Personally I do not recommend feeding a raw food diet. I do have clients who have started a raw food diet of their own accord and the dog is much improved. In these situations we discuss concerns with raw food but we may opt to continue with this diet for the specific individual. Veterinary diets are preferable for the diet trial due to concerns regarding ingredient contamination and the cleaning process of OTC diets. In one study, 3/4 over the counter (OTC) venison canine dry foods with no soy products named in the ingredient list were ELISA positive for soy; additionally one OTC diet tested positive for beef protein with no beef products listed as an ingredient list. Whether to select a novel protein diet or a hydrolyzed diet is a common question I am asked. In multiple studies, up to 50% of dogs with CAFR exhibited increases in clinical signs after ingesting partial hydrolysates from foods to which they were hypersensitive. Also, a proportion of dogs with CAFR will exhibit a worsening of clinical signs when fed partial hydrolysates. Some dogs will greatly improve on these diets as the hydrolyzation process has cut the protein to a size that the individual’s immune system does not recognize. I greatly prefer the use of novel protein diets over hydrolyzed diets unless the patient has GI signs along with cutaneous signs - in this case, the patient could be exhibiting signs of a low grade IBD. A hydrolyzed diet might be a better fit for this patient as the protein is more easily absorbed. During a diet trial, I very often will concurrently start therapy with an oral anti pruritic (Apoquel®) or anti inflammatory (glucocorticoids). I will continue these for the first month-6 weeks of the diet trial to keep my patient comfortable. During the second month I will gradually start to taper off these medications so I can determine whether my diet trial has been successful in eliminating the clinical signs. Pitfalls of Diet Trials

• Multi-pet households and pets sharing food

• In this situation, consider either switching all pets to the same diet or isolating the pet needing the restricted diet

• Bowls should be picked up so no cross contamination can occur

• Family, friends, neighbours, children giving/dropping food

• Treats

• Sometimes there is a treat that can be given during the diet trial

• Alternatively have their regular food where the treats usually are - the pet will still see the benefit of the positive reward

• Three meatball technique for pilling

Outcome After 8 weeks on the restricted diet, you will be left with two scenarios. 1. Your patient is much improved and has been able to discontinue the use of medications.

In this situation an underlying food allergy is highly suspicious. We still cannot definitively diagnose a food allergy as the improvement could have been due to a change in season or another change. To definitively diagnose a food allergy, we would have to reintroduce all previous foods the individual was receiving. If this results in a return of their pruritus within a 14 day period, then we can definitively diagnose a food allergy. In my experience, not many clients like this last step! After years of a pruritic pet they are thrilled the pruritus has resolved. The idea of purposefully allowing the pruritus to return does not interest them. In these cases I will often recommend dietary challenges instead. This is where the diet is continued but individual food items (such as a treat) are introduced back into the diet one a time at specific intervals. It is also important to remember that many patients will have both food and environmental allergies. In these situations there may be only a partial response to the diet trial.

2. The other scenario is that, after 8 weeks on the restricted diet, the patient will still be

pruritic. In this situation the patient has failed the diet trial. I will usually recommend at least 2 diet trials before “calling it quits” on an underlying CAFR and determining it is more likely their pruritus is due to another disease process. **In this situation, this is only if all infections have been treated and resolved as if an infection remains, this alone could cause pruritus and lead to treatment failure.

Although a diet trial should last 8 weeks, it is important to receive updates from clients every few weeks while on the trial. I always tell my clients “things should only get better not worse”. If clinical signs deteriorate this could indicate the individual is having a reaction to something in the diet so we would want to discontinue this diet and switch to a different protein/carbohydrate source. 5 KEY “TAKE HOME” POINTS: 1. An underlying CAFR should be considered in any pet that develops pruritus / clinical

signs prior to 6 months and after 6 years of age, with no previous history of skin disease

2. The majority of dogs who develop an CAFR have been on a diet containing the

offending allergen for years

3. Greater than 60% of patients with food allergies have a minimal to absent response to anti-inflammatory doses of glucocorticoids

4. A restricted diet trial with either a novel protein diet (commercial or home cooked) or

a hydrolyzed diet are the best way to diagnose an underlying CAFR 5. Foods can be reintroduced one at a time during dietary challenges Environmental Allergies (Atopic dermatitis)

Atopic dermatitis (AD) is defined as a genetically predisposed inflammatory and pruritic skin disease with characteristic clinical features associated with IgE antibodies directed against environmental allergens. In most cases, we are dealing with an allergic etiology where the offending allergen cannot be avoided or eliminated from the patient’s environment e.g. if the patient has a pollen allergy, pollens will travel from a 75-100 Km radius. It was once thought that allergens were inhaled into the body. We now know that the largest route of exposure is through percutaneous absorption. Epidermal barrier defects, such as decreased levels of skin ceramides in allergic individuals, are thought to facilitate percutaneous absorption of environmental allergens. During sensitization, the allergens are processed by antigen presenting cells within the skin which then carry these antigens to regional lymph nodes. T cells are activated and stimulate the release of cytokines such as IL-4 and IL-13. This leads to production of allergen specific IgE. The activated T cells then migrate back to the skin. On subsequent exposure, Langerhans cells with allergen specific IgE can rapidly trigger the activation of T-cells, which in turn release pruritogenic cytokines. An excellent explanation along with video of the pathomechanism of allergic dermatitis can be found at http://www.itchcycle.com (Zoetis).

Signalment Atopic dermatitis (AD) is a common diagnosis in veterinary dermatology affecting between 3-10% of the entire canine population. 80% of patients with atopic dermatitis will develop non-seasonal signs and require long-term therapy. Most animals with atopic dermatitis will present with clinical signs between 6 months to 3 years of age. A slightly older onset between 3-5 years is also recognized. There is no known gender predisposition. Breed and geographic region can determine the age of onset with dogs living in warm climates with pollen present year round, more likely to develop signs at a younger age. Definite breed predispositions are noted including, but not limited to Beauceron, Boston Terrier, boxer, Cairn terrier, Shar-pei, cocker spaniel, dalmation, English bulldog, English setter, fox terrier, Irish setter, Labrador retriever, Lhasa apso, schnauzer, pug, Scottish terrier, West Highland white terrier, wire-haired fox terrier and Yorkshire terrier.

History Some patients with AD present with a seasonal pruritus during the warmer months but

more commonly patients present with a non-seasonal pruritus. Clinical signs can also start seasonally, then become year round as the disease progresses. It is important to document whether seasonality is noted to determine whether clinical signs worsen over the next year. Atopic patients may respond temporarily to antimicrobial therapy as secondary infections are treated, but pruritus will return, when therapy is finished. Patients with atopic dermatitis often have a complete response to glucocorticoids, if secondary infections are not present. Another factor influencing the development of AD is the month of birth. Animals born during a high pollen count season, therefore exposed to multiple pollens from birth, appear to be at increased risk for AD. Studies have previously documented certain factors associated with a lower risk of developing AD. These include: living in a rural environment, living in a household with multiple animals and walking in a forest. Up to 30% of patients with AD will have concurrent CAFR, so food should be considered a potential flare factor during periods of increased clinical signs. Clinical Signs Cutaneous Findings

Pruritus is the most common clinical sign associated with AD. This can manifest as actual scratching but is also present when an animal licks excessively, chews or rubs a part of their body. Another common clinical sign of AD is erythema, although not every patient will present with this sign; rare cases will not be pruritic but will present with recurrent secondary infections. Acute cases may also present with scaling, crusting, alopecia and papular eruptions. As the case becomes more chronic, other clinical signs can include hyperpigmentation, lichenification, excoriations and ulcerations. As is the case with food allergies, malodor might be a client’s primary concern and can occur when a secondary bacterial or Malassezia dermatitis is present. Regions on the body commonly affected in cases of AD are the ventral abdomen, inguinal region, axillae, muzzle, periocular region and the flexural surfaces of the forelimbs (patients can often be seen “corn-cobbing” up and down their front limbs). Otitis externa is another common finding. As with food allergies, perianal pruritus can be seen with AD.

Other Related Signs Respiratory Signs - Owners of animals with AD may also report episodes of reverse sneezing along with recurrent rhinitis and/or sneezing. Ocular abnormalities can include increased lacrimation during “allergy season”, ocular congestion and conjunctivitis. Some patients may have mild gastrointestinal disturbances during periods of increased

allergen load within the environment and occasional reports have documented alterations in estrus cycle in affected individuals.

Diagnosis

There is no definitive test for AD so the diagnosis is one of exclusion. Diagnosis is based on history, clinical signs and exclusion of other pruritic diseases via cytology, superficial and deep skin scrapings, fungal cultures etc. In non-seasonal pruritic patients, the differential diagnosis list should include scabies, demodecosis with a secondary infection, dermatophytosis, food allergies and atopic-like dermatitis. In patients with seasonal pruritus the differential diagnosis list should include seasonal ectoparasites such as fleas and lice, atopic-like dermatitis and mosquito bite hypersensitivity. Allergy testing, either intradermal or serologic should not be used as a definitive diagnostic test for atopic dermatitis, but rather as an aid to select appropriate allergens for immunotherapy. In 2010, Favrot documented eight criteria that are often seen in individuals with AD. If 5/8 of these criteria are met, this leads to a high sensitivity (85%) and specificity (79%) in the diagnosis of AD. The criteria are as follows:

1. Age at onset <3 years 2. Mostly indoor animal 3. Corticosteroid-responsive pruritus 4. Chronic or recurrent yeast infections 5. Affected front feet 6. Affected ear pinnae 7. Non-affected ear margins 8. Non-affected dorso-lumbar area

However, up to 20% of cases would be missed if clinicians rely on these criteria alone.

Therapy

Based on the many components of the immune system involved in an allergic response, treatment of atopic dermatitis often involves a MULTI-MODAL approach. A combination of therapeutic approaches is often required and will help minimize the need for more potent medications such as steroids. Ectoparasite control, epidermal repair products, shampoo therapies, essential fatty acids, antihistamines, cyclosporine, oclacitinib, lokivetmab and immunotherapy all work slowly to control and prevent allergy flares with minimal side effects. Due to the number of individuals who have concurrent food allergies and atopic dermatitis, dietary restrictions can aid in the treatment of AD as dietary indiscretions can act as flare factors for these animals. Epidermal barrier repair products that contain ceramides, free fatty acids, essential fatty acids, phytosphingosine, and essential oils are used to repair and maintain an intact

epidermal barrier. This helps to prevent percutaneous absorption of allergens across this epidermal barrier and also prevents adherence of microbes to the skin surface. I often describe the abnormal skin barrier noted in atopic individuals to my clients as, a “crumbly brick wall, with crevices that allergens, bacteria and yeast can get into”. These epidermal barrier repair products help to “fill in the gaps” in the wall! These products should be considered for use as a preventative as well as a topical adjunct to treatment of active clinical signs. I advise clients to apply these products to/next to active lesions as well as following the directions on the packaging. Topical therapy such as bathing. Studies have shown that weekly bathing with a 10-minute contact time with shampoos containing lipids, antiseptics etc can lead to a 25% decrease in pruritus within 24 hrs. If shampoo therapy is possible, appropriate selection of shampoos, based on active ingredients, used with COOL water on a weekly basis will help to treat secondary infections, mechanically remove any allergens on the skin and help repair the epidermal barrier. There is not much evidence in the literature to support the use of specific shampoos containing oatmeal, antihistamines, lipids or glucocorticoids but the benefit stems mostly from the mechanical action of bathing. Many studies document the benefit of using antimicrobial shampoos to treat secondary infections in our AD patients. 0.0584% hydrocortisone aceponate spray (Cortavance®, Virbac) has been shown to reduce pruritus in atopic individuals. With long term use skin thinning might be noted. Topical tacrolimus 0.1% is used in human medicine for atopic dermatitis refractory to glucocorticoids applied topically or in those individuals where topical steroid therapy is not preferable. This is another alternative for topical therapy of AD dogs. Omega-3 fatty acids (EPA - 180 mg/10lbs body weight for dogs) may provide relief for the pruritic individual. Reliable VETERINARY sources should be recommended to achieve optimal responses. Many veterinary products contain a mixture of omega 3 and omega 6 fatty acids. These products may have a lag time of 1-2 months to see the full anti-pruritic effect. Oral fatty acids should not be used during a food trial due to fish based proteins in the oils. Antihistamines have variable efficacy in atopic individuals and one size does not fit all. Cetirizine (0.5-1.0 mg/kg q24h in dogs) is my first choice, based on the availability of pharmacokinetic data in dogs and its action of decreasing influx of eosinophils into affected sites. Second generation antihistamines tend to cause less sedation when compared to first generation antihistamines such as diphenhydramine. Trials with antihistamines are continued for 14 days to assess efficacy. Antihistamines have minimal side effects or contraindications for long-term use. Cyclosporine (Atopica®) is a non-steroidal alternative for treatment of atopic dermatitis in cats and dogs. Cyclopsorine is a calcineurin inhibitor that prevents the release of Interleukin-2 and therefore changes the T lymphocyte immune response. It is useful as a long term symptomatic treatment for AD without the long term side effects of glucocorticoids. Cyclosporine will also decrease IL-3, IL-4, IL-5, tumour necrosis factor (TNF)-α, and interferon (IFN)-α production and serves to inhibit antigen presentation, histamine release from mast cells, neutrophil adherence and growth and differentiation of

B lymphocytes. Cyclosporine is dosed at 5 mg/kg once daily for dogs with both capsules available and liquid (Atopica for Cats®). At these doses it has been documented as being effective for controlling pruritus and inflammation. It may be up to 4 weeks until maximal response is noted. Diarrhea, anorexia and vomiting are the most common side effects and are often transient. Pets in general should not be fed raw food diets while on cyclosporine. Long-term side effects are minimal but gingival hyperplasia is rarely noted in canines on cyclosporine. If an atopic patient presents with inflammation and pruritus, this would be my first choice for therapy as it will address both of these concerns.

Apoquel® (oclacitinib) This medication is the first Janus Kinase (JAK) inhibitor approved for veterinary use that targets itch. It is a selective inhibitor of the JAK-1 enzyme. JAK-1 is involved in the signal transduction of pro-inflammatory cytokines including IL-31. Oclacitinib also inhibits function of IL-2, IL-4, IL-6 and IL-13 (all pro-inflammatory cytokines). Oclacitinib is currently licensed for the treatment of dogs at a dose of 0.4-0.6 mg/kg, orally, twice daily for up to 14 days and then once daily as maintenance. The medication can be given with or without food. Oclacitinib appears to be comparable in speed of onset to prednisolone also. Although oclacitinib has some anti inflammatory properties, I find it best used in patients with pruritus and minimal erythema and skin inflammation.

Cytopoint® (lokivetmab) This is a monoclonal antibody targeting the pruritogenic cytokine IL-31. It is given as an injectable therapy every 4-8 weeks to control ITCH. This injectable will not control inflammation so should not be expected to resolve clinical signs in a patient with erythema and chronic skin changes. There are no listed side effects for the therapy. Most patients will respond within 7 days of receiving the injection. Can be used in dogs of all ages and can be used with many common medications Allergen-specific immunotherapy (ASIT) Allergen-specific immunotherapy (ASIT; also known as allergy shots, hyposensitization) is the practice of administering gradually increasing quantities of an allergen extract to an allergic subject to improve clinical signs associated with exposure to the causative allergen. In an allergic patient there is an exaggerated response to antigens. This exaggerated response is multifactorial and is due to abnormalities of the skin barrier, lipid abnormalities, environmental triggers and genetic predisposition. Dendritic cells of the immune system present antigen to CD4+ T helper cells. Effector T helper 2 cells are then produced and secrete interleukins. This causes B cells to produce IgE as opposed to IgG. IgE cross-linking on basophils and mast cells leads to degranulation and release of inflammatory mediators including histamine (type I hypersensitivity). In dogs with AD, overproduction of Interleukin 4 is due to a Th2 response. In affected animals receiving immunotherapy there is potential shift towards Th1 expression that has been suggested along with an increase in T regulatory cells and IL-10 concentrations. An increase in IgG after at least 6 months of immunotherapy has been documented as well as significant differences between pre and post IgG in dogs with a good response to ASIT compared to those with a fair/poor response. An increase in the ratio of

Th1:Th2 cytokines following ASIT is a consistent finding in both human and veterinary literature. Multiple studies are available outlining the success of ASIT in veterinary medicine. Studies suggest the efficacy of ASIT is anywhere from 50%-100%. This wide range could be due to differing protocols, dose, concentration etc. Some studies found that dogs with non-seasonal pruritus respond better to ASIT but these results are conflicting. The success rate on immunotherapy is based on the reliability of the environmental allergy test. Both intradermal and serologic allergy tests are available. Intradermal skin tests (IDT) are still considered, by most dermatologists,aq to be the gold standard in veterinary medicine as it tests the target organ. However, there are cases where in vitro serologic allergy testing is indicated (cases where anti-inflammatory therapy cannot be withdrawn prior to testing or sedation for the intradermal test is contraindicated). Some dermatologists perform both IDT and serologic testing and formulate immunotherapy based on both test results. Unfortunately, there are differences among the various in vitro companies both in quality and methodology. Reports documenting the efficacy of ASIT based on serological testing versus intradermal testing often show similar results. This finding, however, is not always consistent. Intradermal allergy testing is recommended approximately 90 following the peak allergy season. In year round allergic patients this can be difficult to ascertain. Serologic allergy testing is often recommended prior to the allergy season (again difficult to determine in year round pruritic patients). Twenty percent of pets and up to 40% of humans tested with either in-vitro or intradermal tests will have negative tests. These patients are thought to have “atopic-like dermatitis”. In these cases individuals display clinical signs consistent with AD but no IgE reaction is documented.

Careful consideration of the allergens that are to be included in the extract is critical to the outcome. Too many allergens in a vial might decrease the benefit of ASIT. Many allergens will cross react; not all positives need to go in the vial and most dermatologists limit the number of allergens per vial to 10 - 12. Selection of allergens should be based on the pet's exposure and a detailed history as opposed to the magnitude of the reaction. Allergy extract can be formulated in a number of ways as aqueous extracts (most common) or emulsion extracts. During the induction phase of the ASIT, the volume and concentration of the allergen extract is gradually increased over weeks-months. The maintenance phase is then started where the time interval between injections is increased. Rush immunotherapy involves hospitalization of the patient while the patient is induced over hours rather than days. Adverse reactions documented for ASIT in animals are rare. Animals may become pruritic after an injection, which can be overcome by pre-treatment with an anti-histamine/steroid or the dose schedule can be changed. Systemic reactions (depression, diarrhea, panting, urticaria, collapse, anaphylaxis) are noted in less than 1% dogs. Localized injection site reactions are also rare. It is recommended that owners give shots when they will watch

their pet for a few hours after and when the closest veterinary clinic is open, in case of emergency. Although we do not want to mask the effects of the treatment, anti-inflammatory treatment maybe warranted during the initial phase of immunotherapy to prevent pruritus and secondary infection (especially as it may be a while prior to seeing improvement with ASIT). In dogs improvement can be seen as soon as 3 months into therapy but it can take up to one year. Immunotherapy is the only therapy that may cure atopy (although very rare) or at a minimum prevent the development or progression of allergies. The newer form of immunotherapy is sublingual immunotherapy (SLIT). SLIT involves allergen administration into the oral cavity. Studies to date suggest efficacy is similar to subcutaneous administration. Some patients that fail SQ administration respond well to SLIT. It appears that anaphylaxis may be less common with this route of administration. An “induction” phase is still followed; where the number of drops administered is gradually increased over a few weeks. The patient is then maintained on daily drops long-term. Glucocorticoids can provide immediate relief from symptoms of AD. Oral prednisone or prednisolone (anti-inflammatory doses), dexamethasone (0.05 mg/kg/d) or methylprednisolone (1-2 mg/kg/d) can all be used to decrease inflammation and pruritus and then tapered to the lowest effective dose. Once the clinical signs have resolved, steroids may also be used once daily in 3-7 day bursts to “put out fires’ – I often explain this to clients as a sort of epi-pen for their animals when things get really bad! Long-term inappropriate steroid use can result in recurrent secondary infections, PU/PD, polyphagia, iatrogenic Cushing’s, diabetes, ligament laxity and feline cutaneous hyper-fragility syndrome, to name a few potential side effects. Use of steroids should always be minimized in atopic patients by using the above methods to control clinical signs. 5 KEY “TAKE HOME” POINTS: 1. Atopic dermatitis is a diagnosis of exclusion and allergy testing should NOT be used as a

definitive diagnosis. 2. Atopic dermatitis often develops between the age of 6 months to 5 years and the

pruritus associated with AD is often responsive to glucocorticoids if no secondary infection is present.

3. Treatment often requires a multi-modal approach combining systemic therapy and

topical therapy 4. Treatment for atopic dermatitis will continue life long as AD cannot be cured (unless a

patient is successfully desensitized with immunotherapy) 5. Multiple treatment options for atopic dermatitis exist but, pending the individual’s

clinical signs, they may not be all effective for every AD patient

“Ears Looking at You”: Diagnosis and Treatment of Otitis

Charlie C Pye DVM, DVSc, DACVD

Assistant Professor, Atlantic Veterinary College, Charlottetown, PEI Overview of the Issue Otitis externa (OE) is defined as inflammation of the external ear canal and is a common condition in small animals (4.5-20% of all cases). OE is due to primary, predisposing and perpetuating factors. Primary factors alone can lead to inflammation and otitis development e.g. allergic skin disease, endocrine disease etc. Predisposing factors are present prior to the development of the otitis e.g. anatomy and perpetuating factors occur as a result of the inflammation and include fungal and bacterial infections. The most commonly isolated pathogens in cases of infectious canine OE are Staphylococcus pseudintermedius, Pseudomonas aeruginosa and Malassezia pachydermatis. Cats can also get OE due to primary, predisposing and perpetuating factors. Commonly otitis in cats can also be due to Otodectes cyanotis (ear mites) or aural polyps. Otitis media (OM) is defined as inflammation of the middle ear canal (tympanum to the tympanic bulla). Diagnosis of Otitis Externa Diagnosis of OE is based on history, clinical signs, dermatologic examination, otoscopic examination, cytology and possibly cultures from the external ear canal. As with any dermatologic case, a thorough history should be obtained, especially in cases of recurrent OE. In individuals where otitis is a recurrent or chronic issue despite treatment, this is an indication that the primary cause of the otitis, such as allergic skin disease, endocrine disease etc, has not been addressed. Until this primary factor has been identified and treated, the otitis will continue to occur. A full dermatologic exam of the patient including all areas of the body, not just the ears, may also give you clues as to the underlying etiology leading to development of the otitis. For example, a patient who has come in for otitis externa, on examination displays bilaterally symmetrical hair loss along the caudal thighs and tail - Hypothyroidism could be the primary factor for otitis development. A thorough otoscopic examination is also an important diagnostic tool. Otoscopy will help determine if there is a mass, polyp, foreign body or built up material within the external ear canal. In some cases sedation maybe required for this step to run smoothly. Otoscopic examination may not be possible in all cases, if the external ear canals are stenotic or inflamed. In these cases oral glucocorticoids can be used to decrease inflammation prior to assessing the ear canal. In any case of OE, cytology should be performed to diagnose any secondary infections. There is discrepancy between studies as to how many organisms constitute an infection versus normal flora. For gram-negative rods, even small numbers indicate an infection as they are not usually seen within the external ear canal. When inflammatory cells are noted on cytology, this is a significant finding supporting infection and the number of

organisms is irrelevant. With OE, there is debate as to whether systemically administered antibiotics will reach the desired concentration within the external ear canal. Unless the ear canal epithelium is ulcerated, systemic antimicrobials are unlikely to reach therapeutic concentrations and should be reserved for cases of suspected otitis media. For most cases of OE, topical therapy should be used. Response to topical medication does not often correlate with sensitivity testing results due to the fact that topical medications will reach much higher concentrations within the ear. Therefore the choice of topical antimicrobial should not be based on the culture results but based more on the cytology results. If topical therapy is used to treat OE, a bacterial culture is not required. In cases of OE where gram-negative rods are visualized, a bacterial culture maybe recommended if oral antibiotics are to be used (these cases might be due to Pseudomonas aeruginosa and have ulceration down the ear canal). In cases where previous antibiotics have been ineffective, a culture might also be warranted. Cases of otitis media should always be treated with a systemic antibiotic. Selection of this antibiotic can then be based on a bacterial culture and sensitivity. There is some discordance noted between otic cytology and culture results so always interpret findings in light of cytological findings and clinical signs. Treatment of Otitis Externa If medications are to be given topically, they must be able to reach the surface of the ear canal. In cases where excessive debris is present, flushing of the ear canal under general anesthesia to remove exudate and allow administration of topical products is warranted. At home ear cleaners can be prescribed for patients with instructions to properly clean the ear canal. There are many products available including those with ceruminolytics, anti-inflammatories and anti-microbials, some of which may be the only treatment required. Multiple ear medications are available and many contain antibiotics, antifungals and anti-inflammatory agents simultaneously. Antimicrobials for OE are most often selected empirically based on otic cytology. Current debate over the application of first and second line antimicrobials is ongoing. When cocci are noted on cytology, antimicrobials with action against coccoid bacteria are appropriate. When rods are noted on cytology, otic medications including gentamicin, polymyxin B and enrofloxacin can be considered for treatment. A topical ticarcillin preparation was found to successfully treat Pseudomonas otitis in a small numbers of cases. Tromethamine edetate disodium dihydrate (Triz-EDTA® Aqueous flush, Dechra Veterinary Products, Kansas, US) is commonly used as an adjunct therapy for dogs with Pseudomonas otitis. It has been documented that flushing the canal with Triz-EDTA® 15 minutes prior to the application of a topical antimicrobial agent is beneficial in resolving gram negative infections. Studies also suggest that a chelating agent may be beneficial in cases of Malassezia OE. Neomycin and gentamicin may not always be successful in clearing OE as they are inactivated in purulent material, so maybe best selected when there is scarce pus within the ear canal. For acute Pseudomonas OE, polymixin B is an appropriate choice. For

chronic cases, topical fluoroquinolones or aminoglycosides may be required. The potential for ototoxicity should be determined based on clinical signs and otoscopic examination before any topical products are prescribed. For treatment of Malassezia otitis, clotrimazole, miconazole and nystatin are commonly found in otic medications. Resistance to antifungals has only rarely been reported and there is little evidence for in vitro antifungal resistance. Antifungal medications can be compounded to contain solely an antifungal if the need arises. For inflammatory OE, topical glucocorticoids can aid in decreasing inflammation. In one study a 0.1% Tacrolimus solution was instilled into the ears of dogs without otitis and was well tolerated. With further research this could be an option for inflammatory otitis. Burrow’s with HC is another common anti inflammatory agent used for maintenance of chronic ear disease. For cases of chronic proliferative OE, consider Triamcinolone injections as a salvage procedure prior to total ear canal ablation. Cytology should be repeated at the end of the treatment for the otitis to document that the infection has resolved. If the patient returns 2 weeks later due to otitis, we will then be able to identify that this is a case of recurrence as opposed to a chronic case that never resolved fully. The end point of treatment is when there is BOTH a cytological and a clinical cure. Bacterial biofilms and otitis A bacterial biofilm is a community of sessile bacteria that form layers of planktonic bacterial cells that become irreversibly attached to a surface. The biofilm produces a matrix (extrapolymeric substance, EPS) made of carbohydrates, proteins and DNA. This protects the bacteria from dessication, the host immune response and antimicrobials serving to increase antimicrobial resistance and immune system evasion. A recent study shows 40% of Pseudomonas otic isolates do form biofilms and once a biofilm has formed, this increases the MIC against certain antimicrobials. As with planktonic cells, studies have shown that Triz-EDTA® used in combination with an antimicrobial, can reduce the MIC and minimum bactericidal concentration (MBC) for certain antibiotics against biofilm embedded bacteria. Otitis Media Otitis media (OM) can be a perpetuating factor for cases of chronic OE, leading to incomplete resolution of the otitis. As such, it should be considered as a potential differential diagnosis in any case of chronic OE. If there is an infectious OE and a ruptured tympanic membrane, we can assume that an OM will also be present. However, an intact tympanum does not rule out OM. The tympanum is constantly growing and can heal over an infection within the middle ear. Clinical signs such as a head tilt, ataxia, Horner’s syndrome etc can be noted on examination and are often an indication an OM is present. Most of these signs are indicative of an otitis interna. For

an otitis interna to develop, there is generally an extension of an OM. Some patients with OM display no neurological clinical signs. In these cases, the only way to definitively diagnose an OM is to perform advanced imaging such as a CT scan or an MRI. Infectious OM should be treated with systemic antimicrobials as topical medications will not penetrate deep enough into the middle ear. Appropriate antibiotic selection should be based on cytology and culture results. Ideally a culture sample would be taken from within the middle ear itself but in many cases this may not be possible. In these situations we extrapolate that the results from the external ear canal will the same as those from within the middle ear. Systemic antimicrobials should be continued for a prolonged period of 4-8 weeks. If both an OE and an OM are present, systemic and topical antimicrobials should be used if safe to do so. If the tympanic membrane is intact in an individual with OM, a myringotomy may need to be performed to allow for drainage of material from the middle ear. If a myringotomy is performed, a sterile culture sample can be obtained from the middle ear. 5 KEY “TAKE HOME” POINTS:

1. In cases of recurrent and chronic otitis externa, the primary factor involved in the development of the otitis must be addressed to prevent future recurrence.

2. In cases of otitis externa with stenotic ear canals, anti-inflammatory therapy with

oral prednisone or dexamethasone maybe needed for 7-14 days before otoscopic examination or treatment with topical medication is successful. Most cases of OE will benefit from either topical or oral anti-inflammatory treatment with glucocorticoids.

3. Infectious otitis externa should be treated with topical ear medications whereas

otitis media should be treated with systemic antimicrobials.

4. Otitis media may be a perpetuating factor in cases of chronic otitis externa. These cases might need advanced imaging or a myringotomy for diagnosis/treatment.

5. Bacterial biofilms may play a role in chronic cases of otitis externa.

“So I've Tried X, Y & Z and Nothings Working...What Now?” Charlie C Pye DVM, DVSc, DACVD Assistant Professor, Atlantic Veterinary College, Charlottetown, PEI Overview of the Issue

Frustration can arise when treatment for a particular disease fails to lead to clinical improvement. Other cases may initially improve, but then show a decline. Secondary infections, ectoparasites, development of another disease or adverse drug reactions can all lead to presumed treatment failure. In these cases of “treatment failure”, diagnostic steps should be revisited and further diagnostics may be needed.

Key Diagnostic steps:

When faced with a patient not responding to appropriate therapy, there are multiple steps to take to find out why therapy is not working. First and foremost, client compliance must be checked. The correct dose and frequency of administration must be verified. If the treatment failure involves topical therapy, the owner should be asked how they have been applying or using the topical to make sure application is correct. You can even ask your clients to show you how they have been doing things at home/

Revisit history taking to see if there is additional information you can gather or things that were missed first time around - ask additional questions such as are other pets affected, are humans in the house affected, Any seasonality to the skin disease, has their been a change in clinical signs, what age did the itching start. To make your time as efficient as possible, consider having a questionnaire owners can fill in ahead of time or have technicians take a history first or read cytology samples while you are talking to clients.

Doses of medications and length of treatment should also be revised when dealing with a case of treatment failure. For example, an animal receiving glucocorticoids for atopic dermatitis presents for non-pruritic hair loss. This hair loss may, in fact, be due to the long-term use of glucocorticoids as opposed to the atopic disease.

Attention should be paid to the time of year the pet is presenting to you - the treatment failure may coincide with a change of season and be due to a peak in the number of allergens and a “flare-up” of the patient’s allergic dermatitis. Questions should be asked as to whether there have been any dietary indiscretions that could have triggered a food allergic reaction e.g. was there just a Canada Day barbeque with Uncle Fred who we all know likes to sneak food to the dog under the table!

In allergic patients with previously controlled pruritus, who re-present for pruritus +/- dermatologic lesions, cytology should always be performed to check for the presence of a secondary infection. Secondary infections (bacterial pyoderma and Malassezia dermatitis) are common reasons for perceived treatment failure as they mask the effects of anti-inflammatory therapy. Treatment may involve systemic or topical therapy, or a combination of the two. If left untreated, infections will continue to lead to treatment

failure. Superficial bacterial and yeast infections must be treated for a 4 week period. Deep bacterial pyoderma should be treated for a longer period (8-12 weeks). It is also very important to repeat cytology at the end of the course of antimicrobial to document the infection has resolved and that you are not dealing with a case of antibiotic resistance.

Demodecosis, Sarcoptes or other ectoparasites must also be ruled out via skin scrapings, as they can lead to a worsening of clinical signs in a previously stable patient. An animal receiving high doses of glucocorticoids can develop demodecosis. Flea combing and examination for flea dirt should also be repeated.

Individuals on long term glucocorticoids can begin to show alopecia, erythema, pruritus and papular eruptions that many clinicians will interpret as a “flare up” of the pet’s allergies. Glucocorticoid doses may be increased in these patients. In these cases, it is important to more closely examine and palpate the skin itself. These could be cases of calcinosis cutis developing. Calcinosis cutis can be diagnosed via skin biopsy and treated with topical application of DMSO. Every effort should also be made to wean the pet off of steroids.

Antibiotic resistance has received much attention over the past few years with the incidence of MRSP increasing dramatically. Any animal with a bacterial pyoderma not responding to an appropriate dose and selection of antibiotic, should have an aerobic bacterial culture and sensitivity performed and an appropriate antibiotic selected from the list or antibiotics to which the bacteria is susceptible to.

Approach to treatment failure:

Treatment failure is most often reported when there is a lack of response to glucocorticoids, cyclosporine, oclacitinib or lokivetmab in a presumed atopic dog. If this occurs, there could be an underlying food allergy and therefore it is imperative to perform an adequate novel protein or hydrolyzed diet, restricted diet trial. If a novel protein diet is selected, I prefer diets with exotic proteins due to potential cross reaction of other more common proteins; for example beef and venison. The owner must be informed that no treats, table scraps, pilling vehicles or flavoured medications can be used during the diet trial (that means you Uncle Fred). The diet trial should involve a diet with a novel protein that the animal has not been exposed to previously and should last for 8-12 weeks to determine whether an improvement is noted.

Cutaneous adverse drug eruptions can lead to a worsening of clinical signs. For example, a dog with a secondary bacterial pyoderma due to allergic skin disease, receives a cephalosporin antibiotic and then develops further dermatologic lesions consisting of erythema, alopecia etc. This animal could be exhibiting signs of a cutaneous adverse drug reaction as opposed to a flare-up of allergies. If pruritus occurs primarily in one location where topical products are applied, contact dermatitis should be considered.

In an animal previously responsive to glucocorticoids but now the beneficial effect is waning, consider steroid tachyphylaxis (“steroid fatigue”). The steroid can be switched to another glucocorticoid e.g. oral dexamethasone, Methylprednisolone. If there is a lack of response to a correct dose of cyclosporine, cyclosporine levels can be checked. However, in atopic dogs there does not appear to be a correlation between blood concentrations and clinical response. If the lack of response to glucocorticoids, cyclosporine and oclacitinib, in a patient with atopic dermatitis, is definitively proved and cytology, skin scrapings etc are all negative, one must consider either a case of pruritus refractory to conventional therapy or an incorrect diagnosis. At this point diagnostic steps should be retraced and revised if necessary. Skin biopsies sent for histopathology can also be a great way to help eliminate and identify a diagnosis. Immune mediated disease can usually be diagnosed via histopathology. Other dermatological diseases, such as cutaneous epitheliotropic T cell lymphoma, can present with clinical signs similar to atopic dermatitis but are non responsive to conventional anti-inflammatory therapy. If histopathology is consistent with atopic dermatitis then more aggressive immunosuppressive therapy may be needed in these refractory cases.

Prior to beginning systemic immunosuppressive therapy, all patients should have full bloodwork performed (complete bloodcount and serum biochemistry) as well as a urinalysis. Azathioprine has been used in certain cases to treat refractory canine atopic dermatitis at a dose of 2-2.5 mg/Kg once daily. Further bloodwork is also recommended every 2-4 weeks after starting therapy due to the potential adverse effects such as myelosuppression and hepatic toxicity (increase in ALT, ALP).

Pruritus can originate from regions other than the skin. Pruritus maybe associated with pain or can also be neuropathic. Studies are lacking to document efficacy of the following medications for treatment of pruritus but could be considered in specific cases. Gabapentin is used in humans to treat neuropathic and uremic pruritus. Side effects include sedation and ataxia. Maropitant is a neurokinin-1 receptor antagonist that inhibits substance P. This medication can have an anti-pruritic effect. Maropitant is licensed to prevent and treat vomiting in dogs as a dose of 2 mg/kg once daily. This dose has also been suggested to decrease pruritus.

5 KEY “TAKE HOME” POINTS:

1. In any case where treatment is not efficacious, cytology and skin scrapings should be performed and client compliance should be verified.

2. Consider potential antibiotic resistance in a patient with bacterial pyoderma, confirmed on cytology, which is unresponsive to antibiotics.

3. Taking skin biopsies and sending for dermatohistopathology can provide more information in cases of treatment failure.

4. In certain pruritic cases consider non-conventional therapy or changing the type of glucocorticoid prescribed.

5. In a pruritic patient non responsive to therapy for atopic dermatitis, consider food allergies or cutaneous epitheliotropic T cell lymphoma as an underlying etiology.