2016 Spring.Pdf

1 A message from the President

Dear Friends and Colleagues,

We are happy to welcome you to Birmingham for the 2016 Spring Meeting of the British Veterinary Dermatology Study Group.

This year we are delighted to have two well-known international speakers, Mona Boord and Sonya Bettenay. There will be a vast range of sessions covering the frustrating subject of pododermatitis and claw diseases, from the pathogenesis to the clinical manifestations, to the medical and surgical therapeutic options. I am sure this will provide an ideal occasion for exchange of experiences which will contribute to future education. This meeting aims to educate first opinion practitioners and specialists in the field of veterinary dermatology, supporting and improving the welfare of our patients. I believe that this will be not only an excellent opportunity for all participants to develop further skills in their field of interest but also to indulge in social events.

We have again, fantastic sponsorship for this event creating not only high quality, but outstanding value for money CPD.

Thank you for coming, and we look forward to welcoming you to our 40 th anniversary meeting in the Autumn!

Filippo De Bellis DVM CertVD DipECVD MRCVS European Specialist in Veterinary Dermatology BVDSG President

2 BVDSG Spring Meeting – April 2016 Pododermatitis

Programme & Contents

Wednesday 6 th April

09.00 – 09.30 REGISTRATION

Morning Session – Chair: Filippo De Bellis

0 09.30 - 10.15 Approach to the patient with pedal disease Page 5 Mona Boord

10.15 – 11.00 Interdigital dermatitis, Atopic dermatitis, Demodicosis Page 11 and pedal infections Mona Boord

11.00 – 11.30 COFFEE & COMMERCIAL EXHIBITION

Chair: Carly Mason

11.30 – 12.15 Diseases affecting the pawpads: hepatocutaneous Page 17 syndrome, PF, dermatophytosis, plasma cell pododermatitis Sonya Bettenay

12.15 – 13.00 Diseases affecting the claw and claw bed, SLO, Page 25 dermatophytosis Sonya Bettenay

13.00 – 14.30 LUNCH & COMMERCIAL EXHIBITION

Afternoon Session – Chair: Sarah Warren

14.30 – 15.15 Treatment considerations Page 35 Mona Boord

15.15 – 16.00 Surgical options for pododermatitis (fusion podoplasty, Page 41 onychectomy, laser and cold steel) Mona Boord

16.00 – 17.00 Abstracts: Page 47

Efficacy Of Afoxolander (NexGard ®) Against Canine Mites: Treatment Of Generalised Demodicosis Fred Beugnet and Esther Rawlinson

APPROACH TO THE PATIENT WITH PEDAL DISEASE

Mona Boord DVM, Dip ACVD, Animal Dermatology Clinic of San Diego

Dr. Mona Boord is a veterinarian with specialized training in the field of dermatology. She graduated from the University of California Davis in 1992. She became a Diplomate of the American College of Veterinary Dermatology (ACVD) in 1997. She became an owner and board of director with the Animal Dermatology Clinics with the goal of improving the quality of life of her patients and their families by caring for and improving their skin conditions. Dr. Boord's publications include contributing author of Kirk's Current Veterinary Therapy XIII, Current Therapy in Equine Medicine V, Small Animal Dermatology Secrets, and Veterinary Allergy, as well as publications in several veterinary journals. She teaches dermatology as an Associate Professor at the Western University of Health Sciences, a mentor of multiple residency programs for the American College of Veterinary Dermatology, a national/international speaker and by mentoring visiting veterinarians from abroad. Outside of work, Dr. Boord enjoys competitive performance events with her own dogs including obedience, agility, herding, and tracking.

INTRODUCTION

In order to have the best clinical response to therapy, it is important to have not only an accurate diagnosis, but also to understand that with chronic disease, chronic pathologic change to the tissue may occur. This change can, and often does, hinder therapeutic success.

5 HINT

I often consider chronic pododermatitis the way I compare severe and chronic otitis. They can have predisposing factors, primary factors, secondary or primary infections, and perpetuating factors. It often doesn’t really help to culture the paws. Multimodality therapy is often needed.

EVALUATING THE PATHOGENESIS OF CLINICAL SIGNS

Complicating factors in determining the underlying etiology of pododermatitis in the dog are the large range of diseases that cause pedal disease. The skin only has so many ways to react to disease. As a clinician we appreciate alopecia, erythema, excoriations, lichenification, papules, pustules and other signs that occur with various diseases. The problem is the skin often appears similar in a variety of diseases.

The two most common causes of canine pododermatitis are atopic dermatitis and demodicosis. In the early stages these diseases appear very similar. Both of these diseases may result in secondary folliculitis and pyoderma which appears similar in both cases. The pathogenesis of pododermatitis can be evaluated in the following way , which can help improve therapeutic success. Look for predisposing factors, primary factors, secondary factors, and perpetuating factors.

Failure to address any of these factors will lead to recurrence of disease or failure of therapy. Addressing key features in the history such as age of onset and level of pruritus, as well as evaluating the body areas most affected, allow us to take a long list of differential diagnoses and put them in an order of most likely to least likely causes of the symptoms the patient is experiencing.

PREDISPOSING FACTORS

Predisposing factors are those historical or physical findings that make the patient more susceptible or likely to develop certain conditions causing pathologic changes to the tissue. These factors work in conjunction with either primary causes or combine with secondary causes to cause a patient to be more susceptible to clinical disease. Examples of predisposing factors here would include the following; environmental factors, such as rough terrain or plant burrs; patient care, such as lack of grooming with overgrown claws or interdigital hair mats ; over grooming , such as clipper burns or very short cut hairs may cause inflammation; patient factors, including very short hair coat, abnormal weight bearing (conformation) and/or obesity may cause abnormal weight distribution to the paws.

PRIMARY FACTORS

Primary factors are the diseases or agents that directly induce the problem. The primary etiology may, without any additional factors, cause disease. However, once pododermatitis is present, secondary and perpetuating factors occur, and, in many cases, they become the focus of therapy. As with any medical problem, the primary factors can be broken down into multiple sub-groupings; infectious, immune mediated, keratinization, environmental, congenital, neoplastic, metabolic, and nutritional.

6 The approach to defining the primary factor is similar to any medicine case. Historical evaluation and physical examination help rank the primary factors as more or less likely. The clinician should then base the diagnostic approach on what he or she feels are the most likely differentials. Many clinicians will follow flow-charts and, although they are helpful, they may not be considering the most cost-effective test. Some primary causes of pododermatitis are very inexpensive, yet very important, to rule-out before performing more expensive diagnostic tests; an example of this is ruling out demodicosis prior to allergy testing.

The following is a list of many primary factors causing pododermatitis:

Infectious Bacterial Staph. Intermedius Gram negative or mixed infection Anaerobic infections Fungal Malassezia Dermatophytes Deep mycoses Parasitic Demodicosis Hookworm dermatitis Pelodera Leishmania Dirofilaria immitis Viral Papilloma virus Distemper Cowpox virus (cats) FeLV/FIV

Immune Mediated Allergic Atopic dermatitis Contact allergy Adverse food reaction Autoimmune Pemphigus complex Bullous pemphigoid Systemic lupus

Other Keratinization Seborrhea Vitamin A responsive Digital hyperkeratosis Sebaceous adenitis Environmental Foreign body Trauma Toxin Frost bite Burns Irritant contact reaction Congenital Familial dermatomyositis Zinc-responsive Acral mutilation syndrome Neoplastic Primary Metastatic Paraneoplastic Metabolic Endocrine Hyperadrenocorticism Hypothyroid Hepatocutaneous Syndrome Xanthomas Nutritional Zinc-responsive Vitamin A responsive Miscellaneous Drug eruption Plasma Cell Pododermatitis Onychodystrophy

7 SECONDARY FACTORS

Secondary factors contribute to or cause disease only in the abnormal paw or in association with predisposing factors. Microorganisms act as opportunists and significantly contribute to the inflammation and pathology in the compromised pedal skin. The more commonly isolated bacterial organisms include Staphylococcus pseudintermedius , Pseudomonas spp., Proteus spp. , Escherichia coli , and Klebsiella spp .. Malassezia pachydermatis is the most common yeast contributing to pododermatitis; it is a budding yeast that has a peanut shape. The problem here is the focus of treatment becomes the infection, and the primary etiology or perpetuating factors are not addressed.

When this occurs, more resistant bacterial infections may occur. During consultation, a frequently asked question is “Which antibiotic will best treat this infection?” Perhaps a better question would be “How can this case be better diagnosed or managed?” Changing courses of antibiotics will likely yield more multi-drug resistant microorganisms. The other problem once the occurrence of secondary infection is present is the change in symptoms perceived by the owner. An originally non-pruritic pododermatitis may now be very pruritic.

PERPETUATING FACTORS

Perpetuating factors occur because of alterations in the normal structure and physiology of the paw as a result of predisposing, primary and secondary causes. Perpetuating factors often prevent the resolution of pododermatitis, even when the primary factors are controlled. Pathologic responses are very common with chronic pododermatitis and can lead to permanent changes in the anatomy, which can further lead to persistence of the disease. Inflammation in the skin stimulates epidermal hyperkeratosis and acanthosis, dermal fibrosis, edema, glandular hyperplasia/dilation, and, in some cases, folliculitis and furunculosis.

The tissue swelling that occurs, leads to deep folds and fibrotic nodules in the interdigital tissues. These folds also act as sites for the perpetuation and protection of secondary microorganisms. Regardless of the initial disease process, the clinician is now faced with treating a deep fold dermatitis. These folds and swelling then cause abnormal weight bearing. The pet no longer walks on the pads, but instead starts to walk on the haired interdigital skin, causing further folliculitis and furunculosis, and swelling and fibrosis to occur.

DETERMINING THE ETIOLOGY OF PODODERMATITIS

The history obtained should focus on identifying not only primary and secondary factors, but also predisposing factors, and perpetuating factors. Determine if there is a new or a recurrent problem; if it is a recurrent problem, find out how long it takes to recur once therapy is completed. Determine the age of onset of the disease and what the symptoms of the problem were initially. Ask if disease has been a seasonal problem and if the pet licks or scratches other locations. Find out in what type of environment the pet is kept. Determine what previous therapy has been used and if it was effective completely or partially.

8 ventral interdigital areas should be evaluated. Evaluate the paws for erythema, swelling, comedones, follicular casts, scaling, ulceration, crusting, hemorrhagic furuncles, proliferative growths and/or discharge. If discharge is present, quantify and qualify the type present. Palpate the tissue to evaluate for painfulness and fibrosis or deep nodules. Scarred, nodular lesions warrant a more guarded prognosis.

Chronic interdigital nodular tissue may not return to normal and may be difficult to successfully manage with medical therapy alone. As mentioned earlier the paws are a site affected by many diseases, therefore careful evaluation of the distribution of lesions on the patient, in areas other than the paws, is very important clue to allow the astute clinician to place the list of differential diagnoses in an order of most likely to least likely causes.

A thorough physical examination is very important, as many primary diseases have certain primary cutaneous lesions associated with them. This allows the clinician to develop his or her own flow chart as to what primary etiology is most likely, as well as save the client and patient unwarranted diagnostics or trial therapy. For example, erythema of the paws with normal anatomy, no other primary or secondary lesions, and a history of pruritus in multiple paws, is strongly suggestive of atopy or food allergy; in a 4 month old dog, erythema and comedones are strongly suggestive of demodex.

The discovery of pustules on the foot pads of a cat is almost pathognomonic for pemphigus foliaceus and warrants a biopsy. Crusting at the margins of the footpads and perioral areas is suspect for zinc responsive dermatosis or hepatocutaneous syndrome. Other findings are much less specific, such as interdigital hemorrhagic bulla, which may be due to multiple primary causes.

DIAGNOSTIC TESTS

There is variability in determining which diagnostic tests should be performed; more aggressive versus more conservative approaches are warranted, depending on the individual client. When infectious organisms are suspected, cytological examination is recommended. Cytological examination does not usually establish the primary diagnosis, but it is valuable in determining the type of secondary inflammation and/or infection present. Cytology allows evaluation of the cellular make-up of the discharge, such as the degree of wax, lipids, keratin, neutrophils, or acantholytic cells present.

The sample collected should represent the discharge in the deeper levels of the skin folds, claw folds, draining tracts, or pustules. The samples are smeared onto a glass slide, heat fixed, and stained. Modified Wrights stain is a quick and easy method that adequately stains. The disadvantage is all bacteria stain blue, thus gram staining properties cannot be determined. The presence of white blood cells and intracellular bacteria indicates the body is responding to the infection.

When a mixed infection is noted, with bacteria of various morphology, a culture and sensitivity may be indicated. Cytologic evaluation is the preferred method to determine the role of Malassezia for two reasons. First, cases with Malassezia detected by cytology may culture negative for Malassezia and second it allows for a crude assessment of relative numbers of Malassezia present. Most agree that between 2-3 yeast per high power field is significant and represents yeast overgrowth even without the presence of inflammatory cells. When there is clinical suspicion of infection due to the type of inflammation but no

9 microorganisms are found on cytology, then biopsies with or without deep tissue cultures are indicated.

Culture and sensitivity should not be performed without cytologic evaluation. Cultures are indicated when mixed infections are present, but should not become the focus of therapy. The paws are an open environment walking around on the ground. Bacteria will be present. It is important to evaluate the results of the culture together with your cytology findings. Some organisms, like Proteus sp , will swarm the culture plate and other organisms may be missed. If cocci were the primary finding on cytology but only Proteus is reported, this should be taken into account. Also if rod shaped bacteria were seen on cytology and not grown on the culture, organisms resistant to therapy may still be present and perpetuate the disease.

Biopsy with histopathology is warranted with deep pyoderma. However, it is the author’s opinion that biopsies should be obtained after infection has been treated if organisms are found on cytology. When biopsies are obtained while infection is present, it can be more difficult for the pathologist to commit to a definitive diagnosis due to the background inflammation. The history must be used together with the clinical signs to determine the suspected diagnosis indicates the need for biopsies.

If the primary suspicion is that the patient has an allergy, biopsy results may support that diagnosis, but the money for the biopsy may have been better spent on allergy testing instead. However, if a 10 year old dog is licking and biting its paws and never exhibited these symptoms previously before infections and demodicosis had been ruled out, biopsies would be recommended. Concerns about autoimmune diseases, keratinization defects, and neoplasia all require biopsy with histopathology.

Obviously, many other tests may be needed to make a definitive diagnosis of the primary etiology. Determining which tests are most cost effective and indicated will depend on the history and complete physical examination findings. When the findings are compatible with allergy, allergy testing and/or diet trials may be indicated. If the findings are compatible with seborrhea or other keratinization defects, biopsies may be indicated. If hormonal or metabolic concerns are present, blood panels and hormone level testing may be indicated.

SUMMARY

In conclusion, pododermatitis has many causes and complicating factors which may occur. This requires a diagnostic and therapeutic approach which allows treatment of not only the primary etiology, but also addresses secondary factors and predisposing and perpetuating factors. It is important to have good client communication and multiple evaluations to evaluate response to therapy.

INTERDIGITAL PODODERMATITIS , ATOPIC

DERMATITIS , DEMODICOSIS AND PEDAL INFECTIONS

Mona Boord DVM, Dip ACVD, Animal Dermatology Clinic of San Diego

INTRODUCTION

Interdigital pododermatitis is a common problem in the dog and is less common in the cat. It is a pattern of distribution not an etiologic diagnosis. In order to have the best clinical response to therapy it is important to have an accurate diagnosis. The most common diseases typically seen on the canine paw are canine atopic dermatitis (CAD), demodicosis, and infections such as superficial pyoderma or Malassezia dermatitis. These entities affect the interdigital skin folds and often appear very similar clinically in the early stages of the disease. Accurate diagnosis is key in appropriate therapy.

CANINE ATOPIC DERMATITIS AND THE PAW

Canine atopic dermatitis has an unknown incidence and prevalence based on the ACVD task force review of 2001. 1 Prevalence estimates range from 3-15% but true prevalence is not known. CAD is often reported as the second most common pruritic canine dermatoses. If we look at guidelines for diagnosis of CAD the diagnosis is based on meeting clinical criteria and ruling out other possible causes with similar clinical signs. Elimination diets are required to rule out adverse food reactions (AFR) and then allergy testing can be used to identify potential allergens for allergen specific immunotherapy (ASIT). 2

In a retrospective study out of 266 cases 76% of dogs had distal limb pruritus and/or lesions present on the distal limbs .5 As a tool to assess the likelihood of CAD when presented with a pruritic dog a set of criteria are utilized called “Favrot’s criteria”. These criteria were on review of a large case series of confirmed cases of CAD. Affected front paws are one of eight criteria described in Favrot’s criteria. When six of the eight criteria are met the odds of diagnosing CAD is high. The problem is having affected front paws may not be specific, as other diseases have a pedal distribution as well. Other Favrot’s criteria include an age of onset less than 3 years of age, being a mostly indoor dog, corticosteroid-responsive pruritus, chronic or recurrent yeast infections, affected ear pinnae, non-affected ear margins, non- affected dorso-lumbar area.

In theory, microbial presence may be a trigger to atopy as well as a secondary factor contributing to atopic disease. In a study evaluating Malassezia pachydermatis on skin of atopic dogs, the frequency of isolation of Malassezia from the interdigital skin was 70.7%. 3 In another study evaluating Staphylococcal colonization in atopic versus healthy dogs, 87.5% of atopic dogs were colonized with Staphylococcus pseudintermedius compared to 37.2% of healthy dogs. 4

11 Effects of the skin barrier function and diet also may play a role in the development of CAD. In a study evaluating eleven Labrador retriever dams and eighty puppies, dams were randomly assigned to be fed either a control diet or the same diet supplemented to pantothenate, nicotinamide, histidine, inositol, choline, and pyridoxine to enhance barrier function of the skin. EPA/DHA, n-6 fatty acids and Vitamin E were the same in both groups.

The litters of puppies were randomly assigned into the blinded study as well. The entire litter was fed the same diet corresponding to the diet fed to their mother up to 8 weeks of age. Between 8 weeks and 1 year of age the puppies were fed a growth diet similarly supplemented or unsupplemented. Blood IgE to Der f and Der p was measured at 6 and 12 months of age. At 12 months of age there was no difference in pruritus between the groups based on a questionnaire to the owners. Three dogs from each group had elevated IgE levels and pruritus. After 12 months of age the dogs were followed until 2 years of age to see if they developed symptoms of CAD. During the second year of life diet was not controlled. In the first group fed the control diet 30.3% developed clinical signs and in the supplemented group 8.3% developed clinical signs. P= 0.048. 8

It is very important to consider other differential diagnoses in cases not meeting Favrot’s criteria. It is not common to diagnose CAD in a case that is steroid resistant. Steroid resistance should raise the concern of parasitic, infectious, contact irritant, congenital (stance) and some cases of AFR. Skin scraping to rule out demodicosis should always be performed prior to allergy testing or empirical therapy.

DEMODICOSIS

Demodicosis has many different clinical appearances. The most common lesion is a patch of alopecia. This is typically a disease of the young dog less than 2 years of age or the older immune suppressed dog. Pedal demodicosis is very frequently misdiagnosed in middle aged dogs because the primary veterinarian is not expecting the differential. There are subtle skin changes. First off the “initial” symptoms are not pruritic. It usually isn’t until a secondary infection occurs or when there is a host response that pruritus occurs.

Hyperpigmentation is a subtle sign. The hyperpigmentation is a diffuse blue grey color and is a bit similar to some cases with Malassezia. Comedones may not be easy to find on the paws. Look closely some are white and others are darker. When the condition is a bit more severe a furuncle or draining papule may be noted. The skin tends to be fragile and cut easily during skin scraping. This condition may develop in patients on medications such as chemotherapy, steroids, oclacitinib, or ciclosporin.

SECONDARY FACTORS

12 CYTOLOGY

There is little controversy of the importance of performing cytology when evaluating cases of pododermatitis. However, there is controversy concerning the importance of obtaining culture samples. Lack of repeatability both between and within laboratories is a concern. The cytologic evaluation of material from the interdigital skin is a diagnostic test considered mandatory by most veterinary dermatologists. Once practiced at this technique, the procedure is a simple one, requiring minimal supplies and time.

The most expensive piece of equipment required is a good binocular microscope with a strong light source and high-quality lenses. The minimum lenses needed include a 10x low power scanning lens, a 40x high dry lens and a 100x oil immersion lens. Without a good microscope, cytology can be a frustrating endeavor. The materials required for sample collection are simply a cotton tip applicator or clear tape. The collected debris is applied to a glass slide which is stained for interpretation. Appropriate stains and staining equipment are also required. The stains of choice in clinical practice are Diff-Quik® and new methylene blue. Diff-Quik® is a quick and easy Romanowsky-type stain. It gives less nuclear detail than the supravital stains, such as new methylene blue; however, it allows better differentiation of cytoplasmic structures and organisms.

It is important to realize that normal interdigital skin will have microorganisms present on cytology and that a certain number of those organisms are considered normal. The normal canine paw cytology should find keratinocytes (primarily corneocytes), wax and lipid. Bacteria noted without inflammatory cells is considered bacterial overgrowth and when inflammatory cells are noted and especially with intracellular bacteria a true pyoderma is present.

Cytology allows the clinician to determine if microorganisms present appear to be a pleomorphic or monomorphic population of organisms or if there is a mixed infection of bacteria and yeast. Occasionally fungal hyphae may be found and this organism would be missed if cytology were not performed. Cytology can help to identify the amount of and type of inflammatory cells. Large numbers of neutrophils are often present with a bacterial infection opposed to a primary yeast infection. Yeast overgrowth will rarely exhibit neutrophils.

If a case is cultured, cytology results should always be taken at the time the culture is obtained. Once the culture results are received the results should be compared for compatibility with the cytology recorded at the time of sampling. In a study by Graham-Mize, discordency was found when comparing cytology results to culture results. Thirteen of 50 samples cultured grew more types of bacteria than seen on cytology and 3 of 50 grew fewer. 6 In addition, cytologic evaluation will aid in empirical selection of antimicrobials in the treatment.

CULTURE AND SENSITIVITY (C&S)

In this age of resistant bacterial infections, the use of bacterial culture and sensitivity(C&S) has become a common diagnostic test to recommend and perform when there is chronic pododermatitis.

13 The more commonly isolated bacterial organisms include Staphylococcus pseudintermedius , Pseudomonas spp., Proteus spp. , Escherichia coli , and Klebsiella spp .. Malassezia pachydermatis is the most common yeast contributing to pododermatitis. It is a budding yeast that has a peanut shape. The problem here is the focus of treatment becomes the infection and the primary etiology or perpetuating factors are not addressed. When this occurs more resistant bacterial infections may occur. During consultation a frequent question asked is “which antibiotic will best treat this infection?” Perhaps a better question would be “how can this case be better diagnosed or managed?” Changing courses of antibiotics will likely yield more multi-drug resistant microorganisms. The other problem once the occurrence of secondary infection is present is the change in symptoms perceived by the owner. An originally non-pruritic pododermatitis may now be a very pruritic one.

A C&S is a diagnostic test to identify microorganisms present at the location sampled. There are bacteria on the paws at all times. In a study performed at a Veterinary Hospital in the UK 78 veterinary staff members had nasal and oral mucosa cultures to evaluate the prevalence of methicillin resistant Staphylococcus aureus (MRSA) and 14 staff members (17.9%) were positive for MRSA. 7 Of the other organisms grown 77 staff member’s culture results were positive for a Staphylococcal sp . This raises the issue of the importance of the clinician evaluating the relevance of the results obtained.

When reviewing a culture result it is important to look at the evaluation of growth. This is rarely reported in CFU but may be reported as slight growth, moderate growth or abundant growth. Is an abundant growth of Enterococcus with a resistant profile a pathogen that needs to be addressed with systemic and/or topical antibiotics or will a thorough cleaning of the ear and treatment of the primary disease be sufficient to control this organism? These studies have yet to be performed.

Obviously many other tests may be needed to make a definitive diagnosis of the primary etiology. Which tests are most cost effective and indicated will depend on the history and complete physical examination findings. When the findings are compatible with allergy, allergy testing and/or diet trials may be indicated. If the findings are compatible with seborrhea or other keratinization defects, biopsies may be indicated. If hormonal or metabolic concerns are present blood panels and hormone level testing may be indicated. Don’t forget to skin scape.

SUMMARY

In conclusion, pododermatitis has many causes and complicating factors which may occur. This requires a diagnostic and therapeutic approach which allows treatment of not only the primary etiology but also addresses secondary factors and predisposing and perpetuating factors. It is important to have good client communication and multiple evaluations to evaluate response to therapy.

14 REFERENCES

1. Hillier A., Griffin CE.. The ACVD task force on canine atopic dermatitis (I): incidence and prevalence. Veterinary Immunology and Immunopathology. 2001: 81, pg 147-151.

2. Hensel P., et al. BMC Veterinary Research 2015 11:196

3. Nardoni S. Dini M., Taccini F., Mancianti F.. Occurrence, distribution and population size of Malassezia pachydermatis on skin and mucosae of atopic dogs. 2007: 122, 172- 177.

4. Fazakerley J. et al. Staphylococcal colonization of mucosal and lesional skin sites in atopic and healthy dogs. Vet Derm . 2009 20: 179-84

5. Zur G., Ihrke PJ. White SD., Kass PH. Canine atopic dermatitis: a retrospective study of 26 cases examined at the University of California Davis, 1992-1998. Part I. Clinical features and allergy testing resultls. Vet Dermatology. 2002, 13; 89-102.

6. Graham-Mize CA, Rosser EJ. Comparison of microbial isolates and susceptibility patterns from the external ear canal of dogs with otitis externa. Journal of the American Animal Hospital Association 2004; 40: 102-108.

7. Loeffler, Boag, A, Sung J et al. Prevalence of methicillin-resistant Staphylococcus aureus among staff and pets in a small animal referral hospital in the UK J Antimicrobial Chemotherapy 2005 56, 692-697

8. Looringh van Beeck F. Watson A., et al. The effect of long-term feeding of skin barrier-fortified diets on the owner-assessed incidence of atopic dermatitis symptoms in Labrador retrievers. Journal of nutritional science 2015; 4 p1-6

15 16

DISEASES AFFECTING THE PAWPADS :

HEPATOCUTANEOUS SYNDROME , PF,

DERMATOPHYTOSIS , PLASMA CELL

PODODERMATITIS

Sonya Bettenay BVSc (hons), DipED, MACVSc (Feline Medicine), FACVSc (Dermatology), DipECVD

Sonya Bettenay graduated with an honours degree in Veterinary Science from the University of Melbourne. She has been a member of the Australian & New Zealand College of Veterinary Scientists and the Australian Dermatopathology Society for more than two decades. She obtained her Fellowship in Feline Medicine with the ANZCVSc in the mid 80‘s and her Fellowship in Dermatology in 1991. She is a Diplomate of the ECVD. She has been a board member of the International Society of Veterinary Dermatopathology since 2006 and is a member of the ESVD and the International Society of Human and Animal Mycology (ISHAM). Her teaching activities comprise the Distance Education in Dermatology program with the CVE at Sydney University and dermatopathology training of ECVD residents. She has been an invited speaker at many international and national meetings in many continents. She has co-authored a book on basic Veterinary Dermatopathology with Dr Ann Hargis. Her current research interests focus in the areas of dermatophytes and dermatopathology. Sonya divides her professional time between her clinical dermatology referral practice and an independent dermatopathology service.

Pododermatitis is common in dogs, rare in cats. Diseases restricted to the pad and not involving the haired skin are however not common, but there are some clinical entities and diseases where pawpad disease may be an initial presenting sign and which involve systemic illness and which must be recognised early in the work-up.

Pawpads are anatomically unique. They are characterised by an extremely thick and compact orthokeratotic epidermis, a lack of hair follicles, the presence of atrichial (eccrine) glands and a dense subcutaneous fat layer.

17 FELINE PADS

Pawpad disease in cats is most frequently associated with lesions at other anatomic locations and allergic infectious (viral), metabolic and immune mediated aetiologies.

Congenital pawpad abnormalities observed include (unidentified) bullous diseases – and some of these in the author's experience live comfortably with their disease for many years.

Eosinophilic granulomas are raised, firm and yellowish papules, which may or may not be associated with pruritus. In practice, the most common cause of pawpad lesions is probably the eosinophilic granuloma. However even though some cats present with pawpad eosinophilic granulomas as the sole lesion, more often other additional eosinophilic lesions will be found elsewhere on the body. Importantly, more than one of the recognised feline cutaneous reaction pattern lesions frequently occur simultaneously => so that an eosinophilic granuloma on the pawpad and plaque on the head may occur on the same cat. Those lesions which develop on the pawpad may or may not be pruritic, when present interdigitally they are typically pruritic.

Linear eosinophilic granulomas are clearly defined linear plaques and occur most commonly on the caudal thighs. Granulomas on the head may or may not develop a surface ulceration / inflammation. By far the most common cause of eosinophilic granulomas located on the feline pawpad, in the author’s experience, is mosquito bite hypersensitivity.

Diagnostic procedures of choice are cytology and biopsy. Although the differential diagnoses must include neoplasia, bacterial and fungal granulomas, when the cell type is identified as predominantly eosinophilic with macrophages, then the aetiologic agents considered should be: ectoparasites, dermatophytes and food or environmantal allergies, bacterial infections when present will be typically secondary.

Viral dermatitis Both herpes virus and calicivirus may present with skin lesions, although pawpad involvement is rare and would not be expected to be the sole lesion. As the treatments are aetiologically-targetted and quite specific a confirmed diagnosis is essential. When no investigative tests are allowed and a symptomatic therapy must be chosen, then, as eosinophilic granuloma lesions on the pawpaw are more common , antihistamines are the therapy of choice. Famcyclovir can be initiated when upper respiratory disease is either present or there was a history of URTI.

DISEASES RESTRICTED TO THE PAWPAD

Cutaneous horns have been reported infrequently to form on the pawpad. First described in one FeLV positive cat, subsequently in a group of cats (Scott) from which virus was isolated. But non-FeLV associated cutaneous horns are also recognised. Elsewhere on the body cutaneous horns are associated with SCC and as such one could speculate that papillomavirus may play an as yet unidentified role with some feline cutaneous horns.

Feline plasmacytic pododermatitis (FPP) is a rare inflammatory disease affecting exclusively a single or multiple pawpads of one to all four paws in cats. The precise etiology

18 is unknown. The clinical presentation of feline plasma cell pododermatitis is unique. It is characterized by the presence of a soft, spongy swelling of one or multiple pawpads, which is typically not associated with any sign of pain or lameness. The location has been proposed to suggest contact to external stimuli – but a direct contact irritant is unlikely as only one of the 5 pawpads and often only one or two paws are frequently involved. Most frequently the metacarpal and / or metatarsal pawpad is affected and the digital pads are not, however all pads on all paws may be involved.

An immune-modulated pathogenesis was strongly suspected by the presence of an inflammatory cell infiltrate dominated by plasma cells (hence the name of the disease), the presence of a hypergammaglobulinemia and the response to both immunosuppressive and immunomodulatory therapy. However response to both complete surgical excision of the pawpads and to doxcycline therapy which was discontinued after only 6 weeks speaks against a primary immune mediated disease. An infectious aetiology was considered – based on this clinical response to doxycycline and also in some cases to amoxicillin/clavulanic acid (personal experience), but a study on 14 biopsy specimens of FPP from Australia was unable to find an infectious agent.

Bacille Calmette-Guerin (BCG) antibody as well as PCR to multiple organisms,(Bartonella spp., Ehrlichia spp., Anaplasma phagocytophilum, Chlamydophila felis, Mycoplasma spp., Toxoplasma gondii, and feline herpesvirus 1) were evaluated and selected for several reasons: Bartonella spp., Ehrlichia spp., C felis, Mycoplasma spp., and potentially T gondii have clinical responses when tetracycline derivatives are administered. Another study yielded negative results for 4/4 cats serologically screened for Leishmania spp. and 9/9 screened for feline leukemia virus (FeLV). Although a possible connection with FIV virus has not been so clearly ruled out. Simon and colleagues histopathologically confirmed FPP in six cats with natural FIV infection In one study approximately 50% of cats (20/37) were identified as FIV positive on serology testing.

Feline plasmacytic pododermatitis might be viewed as a reaction pattern with multiple causes and possibly including FIV as a predisposing factor. It has been proposed that an organism may trigger this reaction and then the extreme plasma cell rich infiltrate which results takes on a "life of its own", requiring just that a clinical response results when this is “shut down” … and hence the complete clinical response to multiple therapies.

In general, unless there is concurrent glomerulonephritis or renal amyloidosis, the prognosis for FPP is favorable and spontaneous remission does occur.

My initial approach is always to begin treatment with a 4 to 6 week course of oral doxycyline (paste or liquid, not tablets - due to risk of oesophageal perforation!)

19 CANINE PAD DERMATOSES

Pawpad dermatitis in the dog is relatively uncommon. Typically presentations due to pawpad abnormalities as the sole change are a result of physical damage or trauma – requiring stitches. Running on rough terrain, hot surfaces and sheets of ice may cause extensive pawpad damage but typically in these cases all pads will be affected. Black asphalt can heat up to melting temperature at midday on a hot summer day. Physical elements include broken glass, gravel, metal scraps and salt. History and signalment may help arrive at a diagnosis with pawpad signs. In younger dogs, Distemper is a common cause of hard pad in endemic areas and in very young dogs, a familial pawpad hyperkeratosis (Irish terriers) and a severe, often fatal disease (bull terriers) is recognized, sled breeds may be affected by a zinc-responsive dermatosis.

In young to middle aged dogs, Zinc responsive dermatitis is more common in Siberian Huskies but is also associated with poorly balanced or overmineralised dry dog food. Dogs with abnormal pads due to metabolic epidermal necrosis are older, lame and may show anorexia and lethargy. A number of diseases may have changes restricted to the pad but more commonly involve additional areas of haired skin. These include zinc responsive dermatitis, pemphigus foliaceus, metabolic epidermal necrosis (MEN) (also referred to as superficial necrolytic dermatitis (SND) and hepatocutaneous syndrome). These diseases almost all present with initial scaling and crusting. In older dogs pemphigus foliaceus and hepatocutaneous syndrome (older dogs, not just the pads, often mucocutaneous junctions are affected) are perhaps the most frequent (although both are uncommon).

Congenital diseases affecting predominantly the pawpads include: pawpad hyperkeratosis of Irish terriers and Dogue de Bordeaux and canine Inherited Junctional Epidermolysis Bullosa of German Shorthaired pointers. Lethal acrodermatitis of Bull Terriers typically causes massive pawpad changes but also haired skin. There are however, some more mildly affected Bull Terriers who may present with predominantly pawpad changes. These diseases typically present within the first 4 months of life (LAD and IJEB within 6 weeks), and the latter two are almost always euthanased due to the pain of the lesions. Gene tests are rapidly being developed as the identification of healthy carriers as the only way to control the presence of the disease and to apply a correct breeding strategy.

Physical causes: Two special syndromes are observed which may affect one or multiple pawpads with no associated interdigital haired skin abnormalities and these are the "split pawpad syndome" and an external cause thermal burn (hot pavement)/ salt associated.

"Split pawpad" syndrome has been mentioned in the literature almost exclusively in Gross/Ihrke/Walder. Nevertheless it is a not uncommon cause for presentation and one where the prognosis varies enormously between cases - the clinical disease may be short- lived and relatively mild or severe, extensive, recurrent and resulting in euthanasia!

In split pawpad syndrome, the intraepidermal cleft occurs parallel to the skin surface, as opposed to a fissure or “split” where the cleft is perpendicular to the surface and extends often between epidermis and into the dermis. In some cases there is ulceration, in others erosion. Secondary infection is common and is associated with self-trauma (pain? pruritus?) where the moisture from licking will aggravate the disease progression. I have seen cases which occur once and not again for years, which occur seasonally and recurrently and others which are more frequently recurrent. Systemic antibiotic therapy is often needed, topical may not suffice – but determining the need for antimicrobial therapy via cytology is not always useful. 20

Pemphigus foliaceus is the most common immune-mediated skin disease (together with discoid lupus erythematosus). It can affect adult dogs of any age. The mean age in a bigger study was 4.2 years. Akitas, Chows and Dobermans are some of the more commonly affected breeds. The disease usually begins on the ears and the face. Depigmentation of the planum nasale and/or crusty lesions of the dorsal muzzle, periocular areas and pinnae are the first signs. Paws, pawpads and groin are affected commonly. In some dogs, hyperkeratotic pawpads (with occasional sloughing) are the only clinical signs. Biopsy is the diagnostic test of choice.

Ideally intact pustules are selected but on the pawpads these will almost never be seen. I select a “spongy” area – if palpable, or else a thickened hyperkeratotic area. Pawpad hyperkeratosis may be seen in 15% of dogs with pemphigus foliaceus, but in only 1/5 of these pads will be the only affected sites, more often pustules and/or crusts are seen around the eyes, nose, lips, ears or generalized – and these sites are possibly better to biopsy than a pawpad. Pawpad biopsies should be obtained under general anaesthesia, preferably from the stop-pads of a hind paw. Wounds should be closed well enough to stop any bleeding at the biopsy site and the paw should be bandaged for 2-3 days.

Metabolic epidermal necrosis MEN is a metabolic disorder of unclear pathogenesis and mainly affects older dogs. Amino acid deficiency, glucagon excess, vitamin or zinc deficiency in the skin have all been implicated. Underlying reported causes include liver disease (thus "hepatocutaneous syndrome"), diabetes mellitus (thus "diabetic dermatopathy"), hyperadrenocorticism and pancreatic glucagonoma (thus "necrolytic migratory erythema" - the term used in human medicine for a disease with similar histopathology caused in the majority of patients by a glucagonoma).

Severe crusting and erythema is seen predominantly involving mucocutaneous junctions (lips, perivulvar/prepuce, perianal area), elbows and hocks and pawpads. Lameness is often the reason for presentation. Secondary infections with yeast and/or bacteria are extremely common. Although the associated liver disease is often chronic, many cases have only exhibited any clinical signs over a preceding 6 weeks to few months period.

Classic skin biopsy findings are diagnostic and reveal epidermal hyperplasia and edema, parakeratotic hyperkeratosis and surface crusting. However these changes will not always be obtained, even with adequate numbers of samples! The classic ultrasound appearace of most cases – referred to as “swiss cheese” is almost uniquely associated with this syndrome. If I suspect this disease based on the pawpad appearance, my first test of choice is a liver ultrasound.

Serum biochemistry, liver function tests and/or liver biopsies are important to determine the underlying disease process and its severity, however as the changes are not acute, bile acids and biochemistry findings may all fall within the normal range. The prognosis for patients with MEN generally is poor, although some rare cases stay in remission for months to sometimes up to 2 years with appropriate treatment. The diet should contain high quality proteins (egg whites, body builder protein supplements), essential fatty acid supplementation (serum fatty acids transport Zinc) and oral zinc. In severely affected patients, amino acid infusions are used weekly until improvement is seen (500 ml of amino acids are administered very slowly over 8-10 hours intravenously. Secondary infections are extremely common and control of secondary infections is extremely important for the well-being of these patients.

Zinc-responsive dermatitis Primary nutritional zinc deficiency is rare in small animals. Zinc deficiency due to presumed absorption problems is a more commonly encountered entity. It occurs in either young puppies of rapidly growing breeds or in sled dogs such as Siberian huskies or Alaskan malamutes. Breed predilections suggest a genetic influence of the second syndrome. In Malamutes, a genetic defect leading to decreased zinc absorption in the intestines has been reported. Young puppies fed diets high in phytates or calcium (both of which interfere with zinc metabolism) are reported in the literature - but the current diet formulations are better than these. Iron content in drinking water can also inhibit zinc absorption and has been a cause of clinical signs in my experience.

Skin lesions are usually not restricted to the pawpads. Lesions include erythema in the early phase followed by hyperkeratosis, crusting, alopecia around the mucocutaneous junctions (eyes, mouth, prepuce, vulva), the chin, ears and pawpads with thick crusts over the pressure points. Pruritus may or may not be present, self-trauma of the pawpads is not usual, but lameness may be present. Where deep fissures develop secondary infections are not unusual and may lead to lymphadenopathy. On histopathology, marked parakeratotic hyperkeratosis with eosinophilic serum lakes is compatible with, but not diagnostic of the disease. Diet adjustment may resolve clinical signs without any additional treatment but zinc supplementation will enhance and speed up the response. With genetic zinc absorption problems, zinc supplementation is essential.

Although the equivalent of 1 mg/kg/day of elemental zinc in the form of zinc gluconate, zinc sulphate or zinc methionine is reported as an effective dose, the range in individual dogs goes much higher and varies not only from patient to patient, but also from supplement to supplement. Some dogs will respond to zinc gluconate, but not to zinc sulphate, other dogs vice versa. If a limited response is seen after four weeks, and differential diagnoses have been ruled out, then the dose may be increased. Zinc sulphate is not my first choice as it is more frequently associated with gastric irritation.

Adding small doses of oral prednisolone (0.5 mg/kg/day or less) have been reported to be useful in some dogs (possibly due to enhancing absorption, possibly due to decreasing intestinal inflammation due to a subclinical adverse food reaction that is anecdotally suspected in some of these dogs, possibly due to metallathionine induction). Concurrent fatty acid supplementation is useful in some patients.

TABLE 1:

Differential diagnoses, clinical clues and diagnostic tests for pododermatitis affecting predominantly the pawpads.

DIFFERENTIAL CLINICAL CLUES DIAGNOSTIC TESTS DIAGNOSES Pemphigus foliaceus Breed and age predispositions Cytology of pustules may (“older Akitas”), often pustules reveal acantholytic cells (not and crusts on the face and ears, pathognomonic, but planum nasale frequently involved evidence for the disease), skin biopsy Zinc-responsive disease Arctic breed, frequently crusting Biopsy, response to zinc around the eyes and lips as well supplementation Metabolic epidermal Older dogs. Anorexia and severe Biopsy, ultrasound of the necrosis (SND / depression not unusual, lameness, liver with characteristic hepatocutaneous other lesions around the “honey-comb” / “swiss syndrome /diabetic mucocutaneous- junctions. cheese” pattern or evidence dermatopathy) Biochemistry panel may show of a pancreatic tumor signs of liver damage Idiopathic Young dogs, Irish Terriers, Biopsy hyperkeratosis Dogue de Bordeaux Distemper Dogs systemically ill, poor Biopsy, vaccination history immunohistochemistry Split pawpad syndrome cleft occurs parallel to the skin Cytology (direct angle of surface and involves pawpad only cleft), Biopsy LAD / cIJEB Bull Terrier / GSHP Biopsy / Gene test Plasma cell Swollen foot pads reported in cats Biopsy pododermatitis only, limited to foot pads, often several feet and several pads involved

FURTHER READING

FELINE PAWPAD DISEASES • Bettenay, S.V, et al., Prospective study of the treatment of feline plasmacytic pododermatitis with doxycycline. Vet Rec, 2003. 152(18): p. 564-6. • Bettenay, S.V, M.R. Lappin, and R.S. Mueller, An immunohistochemical and polymerase chain reaction evaluation of feline plasmacytic pododermatitis. Vet Pathol, 2007. 44(1): p. 80-3 • Dias Pereira P 1, Faustino AM Feline plasma cell pododermatitis: a study of 8 cases. Vet Dermatol. 2003 Dec;14(6):333-7. • Guaguere, E., et al., Feline plasma cell pododermatitis: a retrospective study of 26 cases. Vet Dermatol, 2004. 15(Suppl.1): p. 27 • Malik R, Lessels NS, Webb S et al. Treatment of feline herpesvirus-1 associated disease in cats with famciclovir and related drugs. J Feline Med Surg 2009; 11: 40-8. • Preziosi, D. E., Goldschmidt, M. H., Greek, J. S., Jeffers, J. G., Shanley, K. S., Drobatz, K. and Mauldin, E. A. (2003), Feline pemphigus foliaceus: a retrospective analysis of 57 cases. Veterinary Dermatology, 14: 313–321

• Scarampella, F. and L. Ordeix, Doxycycline therapy in 10 cases of feline plasma cell pododermatitis: clinical, haematological and serological evaluations. Vet Dermatology, 2004. 15(Suppl. 1): p. 27.

CANINE PAWPADS

• Fontaine J, Heimann, M., & Day, M. J. Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature. (2003) 14 (6), 279–296. • Gross TL, Song MD, Havel PJ, et al. Superficial necrolytic dermatitis (necrolytic migratory erythema) in dogs. Vet Pathol 1993;30:75-81. • Haines DM, Martin KM, Chelack BJ, Sargent RA, Outerbridge, CA, Clark, EG Immunohistochemical detection of canine distemper virus in haired skin, nasal mucosa, and footpad epithelium: a method for antemortem diagnosis of infection. Journal of Veterinary Diagnostic Investigation September 1999 vol. 11 no. 5 396-399 • Jacobson, L. S, Kirberger, R. M. and Nesbit, J. W. (1995), Hepatic Ultrasonography and Pathological Findings in Dogs With Hepatocutaneous Syndrome: New Concepts. Journal of Veterinary Internal Medicine, 9: 399–404 • Mueller, RS, Krebs I, Power HT, Fieseler KV. Pemphigus foliaceus in 91 dogs. J Am Anim Hosp Assoc 2006 42 189-196. • Outerbridge CA, Marks SL, Rogers QR. Plasma amino acid concentrations in 36 dogs with histologically confirmed superficial necrolytic dermatitis. veterinary dermatology 2002 aug;13(4):177-86. • Romanucci m, bongiovanni l, russo a, capuccini s, mechelli l, ordeix l, della salda l. oxidative stress in the pathogenesis of canine zinc-responsive dermatosis. Vet dermatol. 2011 feb;22(1):31-8. • Van den broek ah, Simpson jwfat absorption in dogs with demodicosis or zinc- responsive dermatosis. Res vet sci. 1992 jan;52(1):117-9. • Van den Broek AH, Simpson JWFat absorption in dogs with demodicosis or zinc- responsive dermatosis. Res Vet Sci. 1992 Jan;52(1):117-9.

DISEASES AFFECTING THE CLAW AND CLAW BED ;

SLO, DERMATOPHYTOSIS

Sonya Bettenay BVSc (hons), DipED, MACVSc (Feline Medicine), FACVSc (Dermatology), DipECVD

INTRODUCTION

Claw disease may or may not be associated with pododermatitis. Pododermatitis is common in dogs, rare in cats. Claw disease is uncommon in dogs and even more rare in cats. Anatomy books describe the gross anatomy of digits and claws. In the early ‘90’s Mueller first described the microanatomy of the normal canine claw in detail and reported the presence of intranuclear vacuolation and dermoepidermal junction clefts. This presumed artifactual change raised the question of previous over-diagnosis of immune-mediated disease. The microanatomy of the feline claw has not been described in such detail.

CLAWS AND COMMON CAUSES OF CLAW DISEASE

FELINE CLAW DISEASE

Most cases referring to “claw disease” in the cat are not in fact claw disease, rather paronychia. Retractibility of feline claws certainly plays a protective role in reducing traumatic damage. Most of the traumatic cases of feline claw disease result from “high speed exits” (accident / near miss involving car or dog) where the cats have shredded their claws in an effort to gain extreme traction. Whether the ability to retract claws also protects the clawbed from external/direct contact with paw-skin infections can only be speculated – as claw dermatophytosis is not a recognised feature in feline dermatology.

The most common cause of paronychia in cats is pemphigus foliaceus (PF). PF typically involves the head region, especially pre-auricular area and pinnae, the paws and/ or is generalised, an exclusive localisation to the paws has been described but is rare. PF commonly produces a fine scale crust affecting the pawpads, often at the margin of the haired skin but also over the entire pad but despite a marked inflammation and caseous paronychia present the claws themselves remain unaffected and are usually not shed.

Clinically, the cats may “flick” their feet and resent their claws being extended, however an actual claw-keratin abnormality is not observed. An absence of claws (anonychia) is usually congenital, although it has been associated with alopecia areata in one cat (Glos, personal communication). In humans, nail changes are frequently associated with alopecia areata and may precede, develop simultaneously, or follow the onset of alopecia

CANINE CLAW DISEASE

Without doubt the most common cause of presentation for claw-disease without dermatitis in the dog is a traumatic avulsion. This typically involves just one claw, is extremely painful but readily remedied and although acutely a secondary bacterial infection is often present, a chronic infectious sequelae is rare. The presence of prominent, blunt to elongated irregular epidermal ridges extending into the superficial dermis in the angle of the dorsal fold presumably adds stability against shear forces. Claw disease involving exclusively and multiple claws is uncommon and there are a limited number of aetiologic diseases to consider. Claw keratin is thick and tough and even a punch biopsy and scalpel will break when used to (attempt to) incise healthy canine claw keratin. Paw and paw-pad dermatitis in the dog is uncommonly associated with claw disease.

INFECTIOUS AGENTS AND CLAW DISEASE

Diseases affecting claws, clawbeds and adjacent haired skin, will most frequently have an infectious aetiology. Bacteria and yeast are the most common infectious agents to produce claw changes, which are observed commonly world-wide. Bacteria and yeast (almost exclusively Malassezia sp .) infections of the haired and paronychial skin frequently result in a visual clawbed brown discolouration easily visible when the claw is not black – but without any associated claw-keratin abnormality. Bacterial paronychia was present in 40% of 196 dogs with claw disease seen at Cornell over a 16 year period (Scott). In those dogs the bacterial paronychia was secondary to hypothyroidism (4 dogs), cushings (2 dogs) and atopy (1 dog). Interestingly pododemodicosis is not usually associated with such claw abnormalities.

Leishmania and dermatophytes can both produce claw abnormalities. Leishmania-associated claw disease is geographically restricted to southern Europe, North Africa and south America. Interestingly dermatophytosis of the clawbed is also seen more commonly in certain countries/ climates. Anecdotally, in one international listserve discussion, clinical cases were observed in Louisianna USA, France/ Spain and South Africa – which are areas where dermatophytosis is (also anecdotally) observed more frequently in general practice. Dermatophytosis, when it affects the claw has typically been “seeded” as a result of trauma to the claw keratin – enabling the fungus access. These cases presumably result from the presence of a high burden of spores on the hairshafts of the paws. The resulting purulent response may be misinterpreted as bacterial in origin.

Leishmania, when it affects the claws, has typically also severely involved the paw haired skin and possibly pads. The resultant claw growth is frequently much larger and twisted with extra long claws (macronychia and onychogryphosis – see table 1).

TRAUMA

In human dermatology, a syndrome associated with typewriting is (was) recognised, where the typists would slough their nails as a result of repeated micro-trauma. This was proposed as a possible mechanism in dogs by Martine Ziener to explain the seasonal loss of claws by hunting dogs in Norway. Traumatic avulsion requires a large amount of force and multiple traumatic avulsed claws is an almost impossible accidental task. A healthy claw is firmly anchored. The microanatomic “folding” of the dermo-epidermal junction provides good anchorage and the attachment extends between claw and the third phalanx.

MULTIPLE CLAW ABNORMALITIES – POSSIBLE CAUSES

In Scott's publication of 196 dogs with claw disease, "onychodystrophy" was caused by: PV (2), PF (2), lupus-like onychodystrophy (7) and was idiopathic (18).

Vasculitis is anecdotally discussed as a possible cause of claw onychomadesis but I have found no publications.

Multiple claw abnormalities (trachonychia) has been reported in two dogs with alopecia areata:- one Rhodesian ridgeback and one mixed breed dog – but in both cases alopecia was also present.

Mineral abnormalities of the claws as a possible cause for onychodystropy / madesis was investigated by Harvey and changes were identified but the aetiologic conclusion was not made. German Shepherd claw mineral changes were noted to differ from other breeds, suggesting a common causality.

MULTIPLE CLAW ABNORMALITIES AS THE ONLY CLINICAL SIGN

SYMMETRIC LUPOID ONYCHODYSTROPHY

Ralf Mueller’s work in claws, that began two decades ago, documented much information, but the actual aetiology of SLO still remains unknown. Breed predispositions have been recognised – with German Shepherds, West Highland white Terriers, Gordon and English setters, bearded collies and Rhodesian ridgebacks being named in reports. Ziener has recently documented a genetic predisposition in Norwegian Gordon Setters. The DLA class II was significantly associated with risk of developing SLO in Gordon setters, thus supporting SLO as an immune-mediated disease. The finding of a positive ANA in Norwegian dogs with SLO was proposed to support an auto-immune aetiology. However interpretation of a positive ANA result must be made with caution. Positive ANA can be identified in dogs with pyoderma (personal experience) and the original Norwegian report (Ovrebo Bohnhorst) also identified positive ANA in cases of black hair follicular dysplasia.

SLO was originally thought to be an immune mediated disease, classified as lupus-like. The pathology of the affected claws showed lupus-like changes (based on the subepidermal clefts and dermal infiltrate) and the clinical picture of multiple sloughing claws was compatible. It has however been recognized that this histopathology may be a so-called “reaction pattern” of the claw and occur in response to many factors including infection. A similar clinicopathologic correlation is recognised with the canine nasal planum – where mucocutaneous pyoderma may be impossible to differentiate from cutanous nasal lupus on histopathology. In addition the clefts may be artifactual.

Breed predispositions have been reported only in Norwegian Gordon Setters. But German Shepherds, West Highland white Terriers, Gordon and English setters, bearded collies, giant schnauzers and Rhodesian ridgebacks are actually named in reports. Ziener has recently documented a genetic predisposition in Norwegian Gordon Setters. The DLA class II was significantly associated with risk of developing SLO in Gordon Setters, thus supporting SLO as an immune-mediated disease. The finding of a positive ANA in Norwegian dogs with SLO was proposed to support an auto-immune aetiology. However interpretation of a positive ANA result must be made with caution. Positive ANA can be identified in dogs

with pyoderma (personal experience) and the original Norwegian report (Ovrebo Bohnhorst) also identified positive ANA in cases of black hair follicular dysplasia.

Clinical presentation SLO cases typically present with a history of one or two claws painfully shed with an assumed diagnosis of trauma. Over the subsequent following weeks either more claws are shed individually or ALL 20 claws are pretty much simultaneously shed. The pain is extreme – while the claw is still attached. Secondary bacterial (paronychial) infections are common. Once the claw has been shed, the pain lessens and the dogs may walk and even run wearing boots to protect the fragile clawbed from trauma. Subsequent to the shedding of the claws, the new claw growth is typically abnormal. The claws are rough, short and fragile – they break and crumble and flake and may infrequently be associated with ongoing clawbed infections and paronychia. These chronic infections will usually be a result of licking / constant self-trauma.

Cause The cause is variable. In the only prospective study, 20% of the dogs were food allergic, with claw disease as the only clinical sign! In this study seasonal allergies were suspected in a few dogs (Mueller). Seasonality was also shown in Norwegian dogs (Ziener). In another study the dogs responded completely to a fish based fatty acid supplement (Bergvall), suggesting an inflammatory but less likely auto-immune-mediated aetiology. Further recent extensive investigation has proven a genetic predisposition (Ziener) and a possible genetic link with Gordon Setters predisposed to hypothyroidism (Ziener).

Ziener has recently documented a genetic predisposition in Norwegian Gordon Setters. The DLA class II was significantly associated with risk of developing SLO in Gordon setters, thus supporting SLO as an immune-mediated disease. The finding of a positive ANA in Norwegian dogs with SLO was proposed to support an auto-immune aetiology. However interpretation of a positive ANA result must be made with caution. Positive ANA can be identified in dogs with pyoderma (personal experience) and the original Norwegian report (Ovrebo Bohnhorst) also identified positive ANA in cases of black hair follicular dysplasia. Hypothyroidism was identified in two dogs by Scott and by the author in two cases, but this has not been identified in the larger studies.

Although an infectious agent has been postulated, due to the clinical response to tetracylines, none have been identified and as the original prospective study was conducted in Australia where at the time blood borne infectious agents were not present the clinical efficacy is considered to be due to the unknown immune-modulating effect of the tetracycline.

Treatment success varies and my “101 multiple claw-only disease” approach is to immediately : • Begin topical antimicrobial therapy as appropriate ( cytology based, see below ) and using antiseptics or creams suitable for use on ulcers (e.g. silver sulfadiazine crème). • Begin an elimination diet – which must be continued for at least 3 to 4 months – as we need to evaluate claw growth and this is slow (no fish oils!) • Initiate an immune modulating therapy (I begin with pentoxyfylline as this may also have some benefit for allergic disease). 28

• Add an essential fatty acid – I use evening primrose oil because it is not typically used by commercial dog food manufacturers (expensive). I avoid fish containing fatty acid supplements for the duration of my elimination diet

As the next step Consider alternative medications such as tetracycline and niacinamide combined (the use of tetracyline is my very last choice due to the extreme world-wide development of antibiotic resistance). Immunosuppression with glucocorticoids has such a low-yield clinical response, that I have not used it in the past 20 years and neither have I needed to use other therapies. Ciclosporin was reported to be equally effective to fish oil in treating symmetric onychomadesis when the dog is fed a diet rich in omega-3 fatty acids (Ziener). Onychectomy has been reported as an alternative successful treatment for severe debilitating, non-responsive disease (Boord) and indeed in Zieners report 3 dogs were euthanized because of the painful nature of their disease. Onychectomy is an alternative to euthanasia and life-long medication.

MY DIAGNOSTIC APPROACH TO MULTI CLAW-ONLY DISEASE APPROACH TO MULTIPLE CLAW -ONLY DISEASE A. History As with any dermatologic problem, a thorough history is crucial. It allows formulating and prioritizing differential diagnoses and choosing the appropriate diagnostic tests to rapidly achieve a diagnosis. Trauma such as a car accident may cause onychomadesis (sloughing of the claws) and secondary infections. An acute onset of disease is more common with autoimmune disease or trauma, while a slow progression is seen particularly with fungal infections or keratinization defects. Systemic signs such as lameness or polyuria/polydipsia may point to specific systemic diseases such as lupus erythematosus involving the claws and/or claw beds. If other animals or humans in the household are affected with skin disease, dermatophytosis may be higher on the list of differential diagnoses.

B. Physical examination A thorough examination should be performed evaluating not only the claws and claw beds of all feet (including the dew claws, if present) but also the skin in general and particularly the mucous membranes, which may show lesions in patients with autoimmune diseases such as bullous pemphigoid or pemphigus vulgaris. If single digits are affected only, trauma is more likely in a young dog. In an older dog with a single digit involved, neoplasia should be considered. An underlying disease process of the bone of the third phalanx may also lead to claw disease affecting only one digit.

Systemic diseases such as autoimmune diseases or food adverse reactions commonly affect multiple digits and typically involve the dewclaws, which are less commonly affected with traumatic events.

Onychorrhexis (brittle claws) may be a result of chronic infection or a degenerative change frequently seen in older dogs, particularly Bull Terriers. Nutritional deficiencies may also cause onychorrhexis.

Inflammation of the claw fold or paronychia may be associated with claw disease and is frequently caused by secondary infection with bacteria or yeast organisms, less commonly and depending on climate and geography – with leishmania or dermatophytosis. DIAGNOSTIC TESTS

DIAGNOSTIC TESTS

A. Cytology Evaluation of claw or claw bed cytology for microorganisms and inflammatory or neoplastic cells is a useful, inexpensive and simple diagnostic tool. Many animals with claw disease will have concurrent paronychia and an impression smear may be obtained by pressing a slide onto the area adjacent to the claw. More useful may be obtaining material from the claw fold and/or claw surface with a swab or small paintbrush. This material is then applied to a glass slide and stained with a modified Wright's stain such as DiffQuick or a Gram stain. Neutrophils with intracellular bacteria are diagnostic for a bacterial infection and antimicrobial treatment is indicated. The presence of bacteria alone may be due to bacterial infection or contamination and clinical judgment will determine the use of antimicrobial agents. Numerous yeast organisms indicate the need for antifungal therapy. However, both yeast and bacteria are rarely primary causes of claw disease and more typically secondary to other disease processes.

B. Bacterial culture I do not commonly use bacterial culture, in a dog which has not been treated with antibiotics. Empirical therapy will resolve most bacterial infections. However, if cytology reveals an unusual organism instead of the typically seen cocci or if empirical therapy with appropriate antibiotics at the appropriate dose fails to resolve the infection, cultures are of benefit.

C. Fungal culture Fungal culture is indicated for all patients where fungal infection is suspected. Prior to culture, the claw may be cleaned with alcohol to reduce bacterial contamination. Scales of the claw fold or the proximal claws, part of avulsed claws and especially scales and hairshafts from the skin adjacent to the claw fold may be sampled. Onychomycoses are common in human dermatology, but fungal organisms rarely cause claw disease in small animals.

D. Complete blood counts, serum biochemistry and urinalysis These tests may be useful in dogs or cats with clinical clues for systemic disease such as hyperadrenocorticism or systemic lupus erythematosus, but have rarely been of benefit in patients with claw disease only. I routinely run a serum biochemistry with resting T4 test.

E. Elimination diet Exclusive claw disease due to food adverse reactions has been reported. An elimination diet for 8-12 weeks using a protein source and a carbohydrate source not previously fed will lead to normal claw regrowth and resolution of clinical signs. Rechallenge with the old diet leads to recurrence typically within days – that means all the claws will slough again!! I rarely have owners willing to risk this.

F. Biopsy Biopsy of the claw, claw matrix and claw fold is essential for the diagnosis of neoplasia or immune-mediated disease such as pemphigus. It may also identify fungal or bacterial organisms. However, interface onychia with vacuolization of basal cells, pigmentary incontinence and a band-like, mononuclear infiltrate has been observed in dogs with confirmed bacterial infections or food adverse reactions and is a reaction pattern of the canine claw rather than a feature diagnostic of immune-mediated disease.

An onychobiopsy technique without the need for onychectomy has recently been described. An 8 mm biopsy punch is used to obtain a sample containing the lateral aspect of the claw and bony third phalanx as well as part of the lateral claw matrix, claw fold and adjacent skin. The technique is very useful, but some practice may be required before diagnostic samples are obtained. It can only be used in diseased and thus softened claws. The alternative is removal and submission of the third phalanx of an affected digit.

G. Radiographs These may be useful for the evaluation of osteomyelitis in dogs with severe swelling and pain possibly necessitating surgical removal of that particular digit.

Table 1: Terminology for claw disorders* Anonychia Lack of claws (mostly congenital) Brachyonychia Short claws Leukonychia Depigmentation of the claw Macronychia Abnormally large claw Micronychia Abnormally small claw (s) Onychalgia Painful claw Onychauxis (Hyperonychia) Simple hypertrophy of the claw Onychia (Onychitis) Clawbed inflammation Onychoclasis Friable / readily broken claws Onychocryptosis (Onyxis) Ingrown claw Onychodystrophie Abnormal claw shape / growth Onychogryphosis Hypertrophy and abnormal formation Onychomadesis (onychoptosis) Loss of claws Onychomalacia (hapalonychia) Softening of the claw Onychomycosis Dermatophytosis of the claw Onychorrhexis Longitudinal growth abnormality, often with ready breakage / abnormal growth Onychoschizia (onychoschisis) Splitting of the claw Onychopathie (Onychosis) Disease or anomoly of the claw Pachyonychia Thickened claw Paronychia (Perionychia) Inflammation / Infection of the clawbed Platonychia Longitudinal flattening Trachonychia Rough accentuated linear ridges *(modified after Scott & Miller; Mueller & Hirose)

Table 2 : Differential diagnoses, clinical clues and diagnostic tests for claw disease DIFFERENTIAL CLINICAL CLUES DIAGNOSTIC TESTS DIAGNOSES Bacterial paronychia Purulent discharge of the claw Cytology, bacterial culture fold Onychomycosis Other animals or humans in the Wood’s lamp, fungal culture, household may be affected biopsy Canine symmetric No other body sites affected, Biopsy, exclusion of lupoid onychodystrophy often affects many claws on differential diagnoses with several or all paws. Reaction cytology, fungal culture, pattern of the canine claw – elimination diet, etc. multiple possible aetiologies Feline pemphigus Paronychia with caseous exudate Cytology of the exudate may foliaceus reveal acantholytic cells (not diagnostic!), skin biopsy Neoplasia Older animal, typically only one Biopsy toe or one paw involved

FURTHER READING

1. Bergvall K, Treatment of symmetrical onychomadesis and onychodystrophy in five dogs with omega-3 and omega-6 fatty acids. Veterinary Dermatology 1998, 9: 263– 268 2. Boord MJ, Griffin CE, Rosenkrantz WS. Onychectomy as a therapy for symmetric claw and claw fold disease in the dog. J Am Anim Hosp Assoc. 1997 Mar-Apr; 33 (2): 131-8. 3. De Jonghe S, Ducatelle v. R, Mattheeuws D R Tachyonchychia associated with alopecia areata in a Rhodesian Ridgeback. Veterinary Dermatology 1999 10 (2), 123- 126 4. Harvey RG, Markwell PJ: The mineral composition of nails in normal dogs and comparison with shed nails in canine idiopathic onychomadesis. Veterinary Dermatology 1996 7:29, 5. Horn M, Viefhues G, Welle MM Trachyonychia associated with alopecia areata in a female mixed-breed dog Kleintierpraxis March 2010 55(3):129-133 6. Mueller RS, Sterner-Kock A, Stannard AA, Microanatomy of the Canine Claw. Veterinary Dermatology, 1993 4: 5–11 7. Mueller RS, Friend S, Shipstone M, Burton G. Diagnosis of canine claw disease - A Prospective Study of 24 Dogs. Veterinary Dermatology 2000 11 133-141 8. Mueller RS, et al. "Influence of long-term treatment with tetracycline and niacinamide on antibody production in dogs with discoid lupus erythematosus."American Journal of Veterinary Research 2002 63.4: 491-494. 9. Mueller, RS Rosychuk, RAW and Jonas, LD. A Retrospective Study Regarding the Treatment of Lupoid Onychodystrophy in 30 Dogs and Literature Review. J Am Anim Hosp Assoc: March/April 2003, Vol. 39, No. 2, pp. 139-150. 10. Mueller RS, West K, and Bettenay SV. "Immunohistochemical evaluation of mononuclear infiltrates in canine lupoid onychodystrophy." Veterinary Pathology 2004: 37-43. 11. Ovrebo Bohnhorst J, Hanssen I, Moen T. Antinuclear antibodies (ANA) in Gordon setters with symmetrical lupoid onychodystrophy and black hair follicular dysplasia. Acta Vet Scand. 2001 42(3): 323-9 12. Pin D, Prelaud P, Guaguere E. Diagnostic Approach to pododermatitis In: Guaguere E, Prelaud P, Craig M, editors. A Practicial Guide to Canine Dermatology Paris: Kalianxis 2008. p 525-533 13. Scott DW, Miller WH: Disorders of the claw and clawbed in dogs. Compendium Continuing Educ. Pract. Vet 14: 1448, 1992. 14. Wilbe M, Ziener ML et al. DLA Class II Alleles are associated with risk for canine symmetrical lupoid onychodystrophy (SLO). 2010 PLoS ONE 5(8): e12332 15. Ziener ML, Bettenay SV, Mueller RS. Symmetrical onychomadesis in Norwegian Gordon and English setters. Veterinary Dermatology. 2008 16. Ziener ML, Dahlgren S, Thoresen SI, Lingaas F. Genetics and epidemiology of hypothyroidism and symmetrical onychomadesis in the Gordon setter and the English setter. Canine Genet Epidemiol. 2015 17. Ziener ML and Nodtvedt A. A treatment study of canine symmetrical onychomadesis (symmetrical lupoid onychodystrophy) comparing fish oil and ciclosporin supplementation in addition to a diet rich in omega-3 fatty acids. Acta Veterinaria Scandinavia 2014, 56:66

TREATMENT CONSIDERATIONS

Mona Boord DVM, Dip ACVD, Animal Dermatology Clinic of San Diego

INTRODUCTION

Pododermatitis is a common problem in the dog and is less common in the cat. The term pododermatitis refers to an inflammatory skin disease that affects the paws. It is a pattern of distribution not an etiologic diagnosis. The paw has many different structures (haired skin, skin folds, claw folds, claws, haired to pawpad junctional skin, and pawpads); the distribution of the disease on the paw helps to determine which differential diagnoses are more or less likely. In order to have the best clinical response to therapy it is important to have not only an accurate diagnosis, but also to understand that with chronic disease, chronic pathologic change to the tissue may occur. This change can and often does hinder therapeutic success.

HINT

I often consider chronic pododermatitis the way I consider severe and chronic otitis. They can have predisposing factors, primary factors, secondary or primary infections, and perpetuating factors. It often doesn’t really help to culture the paws etc… Multimodality therapy is often needed. It is important that the owner understand this for compliance/adherence.

THERAPY / CLIENT EXPECTATION

Prior to recommending therapy, it is important to discuss with the client the multiple potential causes of their pet’s symptoms. The focus of the client is often to “resolve” the pet’s problem. They are frustrated that the problem either doesn’t resolve or appears to resolve but then recurs. Clients often want to know what to feed so their pet “doesn’t get the infection back”. It is important the owner understands if their pet has a primary disease that will likely be ongoing and require maintenance therapy to prevent the secondary infections. Also if secondary infections continue to occur then the primary disease is not adequately controlled at that time.

Clients should also be informed about any perpetuating problems that the clinician perceives and the more guarded prognosis when chronic proliferative changes are present. Then discuss which diseases are most likely and what the most helpful diagnostics will be to determine the main cause of disease. This is most important when the pet has chronic or recurrent disease. If there is concern about disease that will require longer term maintenance therapy, it is important at this point to explain to the owner your suspicions about why the pet is having recurrent problems and if you are correct, what long term maintenance may be required to control the pet’s problems. Discuss with the client that most infections are secondary and will recur unless the primary disease is addressed. Doing this may help prevent some client from changing veterinarians multiple times looking for a “cure”.

SECONDARY FACTORS

Next is to treat any secondary problems like bacterial and yeast infections. The most common error in treating a chronic pododermatitis complicated by bacterial infection is discontinuation of the antibiotics prior to full resolution of symptoms. The concern is not only the problem of not clearing the current infection, but in selecting for bacteria more resistant to the current microbial therapy. When there are perpetuating changes associated with scarring, prolonged use of antibiotics up to 12 weeks may be needed.

This infection needs to have the respect of trying to resolve an acral pruritic nodule (APN). Just as treatment for an APN is judged on palpation of the lesion, palpation of the interdigital scar tissue is very important during follow up examination to determine the effectiveness of therapy. The length of therapy depends on the response, the occurrence of super infections, and the deep microabscesses and fibrosis present. In this day of antimicrobial resistance, combination antibiotic therapy may be required.

Please note there are two other very important factors that need to occur during the treatment of the deep infection for maximum success in therapy.

One, topical therapy is important to control opportunistic microflora while obtaining control of the current infection and primary disease. If Malassezia is present then topical antifungal therapy is indicated. If the infection is more severe or refractory to therapy then systemic anti-fungal therapy may be indicated. Superficial bacterial overgrowth without purulent “pyoderma” will slow response to therapy and be a foothold for recurrent infection.

The second factor is determining and controlling the primary underlying cause early in treatment will resolve the condition in a more timely manner. Similar to a chronic otitis with a stenotic ear canal, steroids will help decrease the inflammation in chronic proliferative pododermatitis. However, using both antibiotics and steroids together initially makes evaluating the response to antibiotics much more difficult. In addition as diagnostic testing of primary causes are required, such as allergy testing, thyroid evaluation or biopsies, steroids may influence the results of those tests.

PRIMARY FACTORS

CANINE ATOPIC DERMATITIS (CAD)

If the history and clinical signs are compatible with canine atopic dermatitis (CAD) and steroids are indicated to help control marked proliferative tissue, perform the allergy testing early in the evaluation process, so steroids may be utilized to control the proliferative tissue. Please realize that blood allergy tests may have false positive results and should not be used to diagnose atopic dermatitis but to select allergens for immunotherapy, preferably after a food elimination diet trial and parasitic control is performed. Allergen specific immunotherapy can be postponed while flea control and diet trials are performed if needed, but the owner will be much more compliant if their pet is comfortable during these initial weeks of therapy. Also if there are several strong positive test results on a skin allergy test the decision may be made to start allergen specific immunotherapy (ASIT) sooner in the course of therapy.

Treatment of CAD usually multimodality therapy involving a combination of avoidance, topical therapy, antihistamines, glucocorticoids, oclacitinib, ciclosporin (Csa) and/or essential fatty acids. I tend to avoid oclacitinib (Apoquel) in these cases initially if there is concern of deep infection. Interdigital cysts are listed as clinical observations likely to be related to oclacitinib. My goal of therapy is to keep the pruritus level to a 4 or less on the Pruritus Visual Analog Scale (PVAS) and to minimize secondary infections to less than 2 bouts of pyoderma or otitis per year using the safest combination of medications allowing the minimal use or lowest dosing of glucocorticoids, oclacitinib or ciclosporin possible.

Therefore a typical instruction for the owner is to maintain a bathing, and ear flushing protocol, use of a leave on topical product as a preventative for microbial overgrowth or to decrease inflammation, ASIT, continue good flea control and to keep a dermatology supportive diet consistent. Then if there is still the need the owner is given additional medications to add to the protocol for times the PVAS increases above 4. An owner willing to provide good topical therapy to a problem paw disease, can save themselves and their pet many trips to the veterinarian.

ADVERSE FOOD REACTION

If adverse food reaction (AFR) is a differential, then an elimination diet for 8-12 weeks is indicated. In order to assess the post diet challenge, the challenge needs to be performed independently from finishing anti-microbial therapy or discontinuation of glucocorticoids or other immunotherapy. This may require a commitment to continuing the diet for a longer period of time if there is a good response to the initial 8 weeks of therapy. If medications are being used as an antibiotic or flea control during the diet trial this includes not dispensing the medication in a chewable form. I will often continue a diet trial longer than the 8 weeks if the pet is continuing to improve and we have not tapered off other systemic medications such as antimicrobials, steroids, or immune modulators. I also will rarely ask a client to perform a diet challenge during the spring or fall if some symptoms of disease are still evident.

DEMODICOSIS

In cases of pododemodicosis, Isoxazolines are quickly becoming the treatment of choice. For decades there have been problems in treatment of chronic pododemodicosis as many of the topical therapies such as amitraz or Advocate failed to control pododemodicosis. Ivermectin was effective but could not be used in many breeds and is off label use for demodicosis. The newer antiparasitic isoxazolines are being shown to be very effective in control of demodicosis and are licensed for use for flea control. The primary clinician is quick to utilize this therapy for flea control and to prevent demodicosis while using immune suppressive drugs or immune modulating drugs to control allergic symptoms instead of exploring ASIT or diet trials.

BACTERIAL OVERGROWTH / PYODERMA / DEEP PYODERMA / FURUNCULOSIS

Treatment of bacterial infections of the paw vary depending on the severity of the “infection”. In mild cases of digital inflammation the heat of the interdigital spaces creates an environment for bacterial overgrowth. In these cases management with products to improve the epidermal barrier by replacing ceramides and free fatty acids may be helpful. Products which lower bacterial levels such as shampoo, topical leave on products, are beneficial. When

a true infection is present with intracellular bacteria the systemic antibiotics are utilized while addressing the primary cause. Length of therapy will be determined by response to therapy and ability to control the primary disease.

STEROID USE

If the severity of the paw disease is likely to require steroids and a biopsy is needed to determine the primary etiology, the decision to start glucocorticoids is a bit more complicated because we would like the secondary infection to be controlled prior to obtaining the biopsy sample as secondary infection and anti-inflammatories will affect the histopathology results. I will typically treat the secondary infections for 2 weeks and then recheck to obtain the biopsy samples once the infection is resolved or less severe. This decision is on a case by cases basis. Interestingly, despite the severity of clinical signs, many immune mediated diseases of the paws, such as Pemphigus foliaceus, have little secondary infection. This can be determined with cytology findings. In these cases the biopsy sample should definitely be obtained prior to initiating glucocorticoids.

DERMATOPHYTOSIS

Therapeutic options for dermatophytosis include a combination of topical and systemic therapy. The topical shampoos should contain a miconazole-chlorhexidine or climbazole- chlorhexidine combination. Rinses with lime sulfur may be performed or leave on wipes with anti-mycotic ingredients are used. Systemically Terbinafine, Itraconazole, and Fluconazole are the most frequently used therapy. Griseofulvin is no longer used by the author.

KERATINIZATION DISORDERS

If histopathology indicates a keratinization abnormality, therapy will depend upon the ultimate diagnosis. Vitamin A, zinc, retinoids, ciclosporin are systemic therapies utilized for various conditions. Topical therapy includes degreasing topical such as tar, benzoyl peroxide, or keratolytic agents such as sulfosalicylic acid shampoos. Moisturisers such as alpha keri bath oil, fatty acids and essential oils in Dermoscent essential 6, and phytosphingosine are helpful adjunctive therapy.

AUTO IMMUNE DISEASE

If the primary disease is an autoimmune process then the prognosis often becomes more guarded. Pemphigus foliaceus is the most common immune mediated disease of the paws. Initial therapy is typically glucocorticoids and most commonly prednisone or methyl prednisolone at 2-4mg/kg divided daily. If the response to monotherapy is not satisfactory then the addition of azathioprine at 2mg/kg daily or ciclosporin 5mg/kg daily is the next step taken by many clinicians. The author finds these cases very rewarding to treat but therapy can be costly and require significant re-evaluations and monitoring. A dedicated owner understanding the long term goal is very important. Most immune mediated diseases are complicated to treat and the success rate of therapy in the hands of a dermatologist seeing these cases routinely is fair to good. These diseases require frequent modification of medications to provide the fewest side effects and best response to therapy so please consider referral to a dermatology specialist.

Vasculitis is a frustrating disease entity due to the difficulty in determining the primary etiology. In some cases, such as a vaccine site reaction, the trigger factor is apparent. But in most cases the disease is idiopathic in nature. Some of these cases are doxycycline responsive and it is unclear if we are treating a primary infectious trigger yet to be discovered or difficult to identify with current diagnostic tests available. Others respond well to Pentoxifylline 25- 30mg/kg bid.

Another poorly understood disease entity is lymphocytic-plasmacytic pododermatitis or immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis published by Breathnack in 2005. 1 Therapy for these initial cases included prednisolone 2mg/kg po daily or ciclosporin 5mg/kg daily. Over time, maintenance doses on prednisolone could be tapered to 0.4 – 1.0 mg/kg q 48 hours and ciclosporin could be tapered to 1.5-4.5 mg/kg q 48 hours. In large breed dogs or patients not tolerating the side effects of ciclosporin the author has used azathioprine as a monotherapy for maintenance in these cases with good success.

Doxycycline responsive diseases such as vasculitis or feline plasma cell pododermatitis raise the question; are we modulating the immune system or treating an infectious disease triggering an immune mediated event? In a recent report of 10 cats with plasma cell pododermatitis (4/9 positive for FIV) 5 cats went into complete remission (one cat in 30 days and 4 cats in 60 days), another 4 cats improved greater than 50%, one cat was lost to follow up and one had no improvement. 2

METABOLIC DISEASES OF THE PAW

Superficial necrolytic dermatitis , hepatocutaneous syndrome, metabolic epidermal necrosis, necrolytic migratory erythema is a disease with a cutaneous marker of internal disease. The most common internal finding is a cirrhosis of the liver. This leads to marked deficiencies in amino acid levels. This disease is also seen with glucagon-secreting pancreatic tumours. Both entities have a guarded to grave prognosis depending on the stage of the disease and the ability of the liver to regenerate pending the cause of the liver insult. Therapy involves initially getting amino acids into these patients. If the liver is to try to regenerate it needs nutrition. Any medications previously utilized that may damage the liver should be discontinued if possible. These are usually NSAIDs. Unfortunately some anti-seizure medications may be implicated and often cannot be discontinued.

CONGENITAL DISEASES OF THE PAW

Hyperkeratosis of the pawpads may be seen as a congenital problem in many breeds. They present with pain and very thickened pawpads. These may form fronds of keratin, horns, or thick hard pads that fissure and create pain. Therapy involves attempts to soften the paws with water soaks, urea topicals can help pull water into the tissue. Then filing or dremeling the excessive keratin or trimming the fronds in a manner to allow more correct weight bearing can be very helpful. This requires life-long therapy.

ABNORMAL WEIGHT BEARING

When chronic perpetuating factors prevent continued improvement or continue to cause relapses then surgical removal of interdigital nodules or deep interdigital folds may become necessary. This procedure is called podoplasty. A complete podoplasty involves removing all of the interdigital skin dorsally and all the haired skin ventrally on the paw. This is a tedious surgery, but very doable. For some patients there is a marked improvement in the quality of life and marked decrease in recurrent disease. Potential complications can include fissures at the junction of the central pad and digital pads ventrally.

SUMMARY

In conclusion, pododermatitis has many causes and complicating factors which may occur. This requires a diagnostic and therapeutic approach which allows treatment of not only the primary etiology but also addresses secondary factors and predisposing and perpetuating factors. It is important to have good client communication and multiple evaluations to evaluate response to therapy.

REFERENCES

1. Breathnach RM. Baker KP et al (2005), Clinical, immunological and histopathological findings in a subpopulation of dogs with pododermatitis. Veterinary Dermatology , 16: 364-372 2. Scarampella, F. and Ordeix, L. (2004), FC-22 Doxycycline therapy in 10 cases of feline plasma cell pododermatitis: clinical, haematological and serological evaluations. Veterinary Dermatology, 15: 27.

SURGICAL OPTIONS FOR PODODERMATITIS

(F USION PODOPLASTY , ONYCHECTOMY , LASER ,

AND COLD STEEL )

Mona Boord DVM, Dip ACVD, Animal Dermatology Clinic of San Diego

INTRODUCTION

Pododermatitis is a common problem in the dog and is less common in the cat. The term pododermatitis refers to an inflammatory skin disease that affects the paws. It is a pattern of distribution, not an etiologic diagnosis. The paw has many different structures (skin, skin folds, claw folds, claws, haired skin, pad junction, and pads), and distribution of the disease on the paw helps to determine which differential diagnoses are more or less likely. In order to have the best clinical response to therapy, it is important to have not only an accurate diagnosis, but also to understand that with chronic disease, chronic pathologic change to the tissue may occur. This change can and often does hinder therapeutic success.

PATHOGENESIS

A complicating factor in determining the underlying etiology of pododermatitis in the dog is the large range of diseases that may cause pedal disease. The pathogenesis of pododermatitis can be evaluated in the following way which can help improve therapeutic success. Look for predisposing factors, primary factors, secondary factors, and perpetuating factors. Failure to address any of these factors will lead to recurrence of disease or failure of therapy.

PERPETUATING FACTORS

Perpetuating factors occur because of alterations in the normal structure and physiology of the paw as a result of predisposing and primary causes, as well as the response to secondary infections. Perpetuating factors often prevent the resolution of pododermatitis even when the primary factors are controlled. Pathologic responses are very common with chronic pododermatitis and can lead to permanent changes in the anatomy and can result in persistence of the disease. Inflammation in the skin stimulates epidermal hyperkeratosis and acanthosis, dermal fibrosis, edema, glandular hyperplasia/dilation, and in some cases, folliculitis and furunculosis.

The resultant tissue swelling leads to deep folds and fibrotic nodules in the interdigital tissues. These folds also act as sites for the perpetuation and protection of secondary microorganisms. Regardless of the initial disease process, the clinician is now faced with treating deep fold dermatitis. These folds and swelling then cause abnormal weight bearing. The pet no longer walks on the pads but starts to walk on the haired interdigital skin causing further folliculitis and furunculosis, swelling and fibrosis.

Lupoid onychodystrophy is a rapid onset and debilitating disease affecting most, if not all, of the claws in affected dogs. When these cases are presented early in the disease, there are great medical therapies available to control the disease and return these patients to full function. However, if this disease progresses without appropriate therapy, if there is a lack of response to therapy, or if the patient cannot tolerate therapy, then onychectomy may be necessary.

CLINICAL EVALUATION OF THE PAW

Physical evaluation of the patient with pododermatitis should determine multiple clues to the underlying etiology. First, assess the conformation of the paw. Is normal weight distribution present? The anatomy of the paw is complex. Determine the distribution of the disease on the paws including how many paws are diseased. The claws, claw folds, pads, and dorsal and ventral interdigital areas should be evaluated. Evaluate the paws for erythema, swelling, comedones, follicular casts, scaling, ulceration, crusting, hemorrhagic furuncles, proliferative growths and/or discharge. If discharge is present, quantify and qualify the type present. Palpate the tissue to evaluate for painfulness, and fibrosis or deep nodules. Scarred nodular lesions warrant a more guarded prognosis. Chronic interdigital nodular tissue may not return to normal and may be difficult to successfully manage with medical therapy alone.

Neoplasia may also develop on the paw requiring digital amputation or partial paw amputation. A ten year retrospective study evaluating eleven dogs with partial foot amputation for treatment of neoplasia was reviewed.4 The most common tumors (six of the eleven) were mast cell tumors, two of eleven tumors were osteosarcoma, and one each of Squamous cell carcinoma, synovial cell sarcoma, and soft tissue sarcoma. In the two osteosarcoma cases, one was extraskeletal, had adjunctive cisplatin therapy, and was still alive 455 days out; the other had chemotherapy, developed metastatic disease to the lungs at day 634, and was still alive at day 962.

The case with squamous cell carcinoma had metastasis to the lymph node at day 157, had the limb amputated and was alive at day 1312. The patient with synovial cell sarcoma had limb amputation as adjunctive therapy and was alive at day 1766. Of the remaining six cases with mast cell tumor (all grade II), five of the six were between the 3 rd and 4 th digits. One of the six had adjunctive radiation therapy, but this case died at day 464. The remaining five had no additional therapy. One is alive at day 819, one is alive at day 1198, one died at day 1144, one died at day 2561, and one is alive at day 3028. 4

THERAPY

Prior to recommending therapy, it is important to discuss the multiple potential causes of the pet’s symptoms with the client. This should include a discussion about the perpetuating problems that the clinician perceives and the more guarded prognosis when chronic proliferative changes are present. Then discuss which diseases are most likely and what the most helpful diagnostics will be to determine the main cause of disease. This is most important when the pet has chronic or recurrent disease. If there is concern about disease that will require longer term maintenance therapy, it is important at this point to explain to the owner your suspicions about why the pet is having recurrent problems, and if you are correct, what long term maintenance may be required to control the pet’s problems. Advise the client that most infections are secondary and will recur unless the primary disease is addressed. Doing this may help prevent some clients from changing veterinarians multiple times looking for a “cure”.

Next is to treat any secondary problems like bacterial and yeast infections. The length of therapy depends on the response to therapy, the occurrence of super infections, and the presence of deep microabscesses and fibrosis. At this point, starting steroids is usually contraindicated. Using both antibiotics and steroids together initially makes evaluating the response to antibiotics much more difficult.

If the history and clinical signs are compatible with atopic dermatitis or food allergy consider performing an allergy test or start an elimination diet for eight weeks. Owner compliance is also important when recommending an elimination diet; be sure that the owner understands that nothing else, except for the specified diet and water, is to pass the pet’s lips for a period of eight weeks.

When chronic perpetuating factors cause abnormal weight-bearing, and deep follicular cysts prevent continued improvement or cause recurrent cysts, then surgical removal of interdigital nodules or deep interdigital folds may become necessary; this procedure is called fusion podoplasty. The first article presented in 1991 by Swaim and a newer publication in 2011 by Papazoglou have reviewed cases and describe this surgical procedure in detail 1,2 . This is a salvage procedure similar to a total ear canal ablation being a salvage procedure in chronic proliferative otitis.

A complete podoplasty involves removing all of the interdigital skin medial and lateral to the digits and all the haired skin on the ventral paw. This is a tedious surgery but can be performed. For most patients there is a marked improvement in the quality of life and marked decrease in recurrent disease. Potential complications can include fissures at the junction of the central pad and digital pads ventrally.

A partial fusion podoplasty is an option when only part of the paw is involved in the disease process. The goal is to remove the scar tissue and improve the weight bearing of the patient.

SURGICAL PROCEDURE

The paw is surgically clipped and prepared with surgical scrub. A tourniquet is applied over the metacarpal or metatarsal area. The incision is started on the dorsal paw. The incision is made to remove the lateral and medial skin from the digits leaving the skin dorsally to cover the dorsal digit. On the lateral fourth digits and medial third digit, enough skin must remain on the paronychia to cover the digit to allow for the second and fifth digits being shorter. Blunt dissection is used to separate the scarred tissue from the digital nerves and blood vessels.

Depending on the amount of time this takes, the tourniquet is released for several minutes to allow blood flow and prevent thrombi. Then the ventral interdigital haired skin is excised. The only tissue that should remain is the central and digital pad tissue. One should attempt to remove all hair follicles. The paw is then soaked in dilute chlorhexidine and flushed with saline. A ¼ inch penrose drain is placed between the central pad and digital pads. The digital pads are opposed to each other and to the central pad. The dorsal skin is then closed. The paw is bandaged in a splint to prevent extension of the paw. The bandage should apply enough pressure to prevent excessive bleeding but not be so tight as to create ischemic damage. The bandage is changed in 6-12 hours and is initially changed every other day. The drain is removed in 2 days. The bandage can be applied without the splint in 10-14 days.

The main side effect with this procedure is separation of the digital and central pads. This will then heal by secondary intention. In one study evaluating 7 dogs one developed necrotized fasciitis.

A variation of the full podoplasty has been published about dogs with abnormal weight bearing that has created thickened scar tissue on the medial aspects of the fifth digits and deep interdigital cysts. In this surgery the CO2 laser is used to ablate the abnormal tissue and the skin is allowed to heal by second intention 3.

The author also utilizes a partial podoplasty technique that has yet to be published. This method is a blend of the fibrous tissue removal and the full podoplasty and is especially helpful when there is abnormal weight bearing as a predisposing/primary cause. Basically the fibrous scar tissue is removed as well as any haired skin that will create a deep fold during healing. But instead of allowing the lesion to heal by second intention where the abnormal weight bearing could create a new callus formation, the affected pads are opposed to improve the weight bearing on the paw.

Partial foot amputation is a modification of the technique used to amputate a single digit. These amputations may be at the metacarpal/metatarsal phalangeal joint or at the distal carpal/tarsal joint pending tumor size and margins. In the above mentioned study of the eleven dogs with partial paw amputation, nine of the eleven had mid-foot amputations removing digits 3 and 4. In regards to the other two cases, the patients had lateral-foot amputation of digits 4 and 5. All dogs had lameness following surgery, and eight of the dogs returned to normal function. Time for lameness to resolve was 1-180 days with a 37 day average. In one of the cases lameness persisted due to radiation burns to the digital pads. In conclusion, long term tumor control was good. 4 Only two of ten cases (excluded one with adjunctive limb amputation) found metastasis after a median follow up time of 962 days. 4

Onychectomy is recommended for chronic relapsing claw disorders causing pain and discomfort persistently or repetitively to the patient that is less responsive or non-responsive to medical therapy.

In one study, six of seven dogs undergoing surgical onychectomy were apparently pain free and their lameness eliminated. 5 The key to this procedure is to give the dog a normal digit to stand on following surgery. If not performed properly a partial podoplasty or full digit amputation could be warranted in the future. The paws are surgically prepared and a tourniquet applied. An incision is made 2mm proximal to the claw fold from medial to lateral across the dorsal aspect. The digital extensor tendon and dorsal elastic ligament are transected. The medial and lateral collateral ligaments are transected.

The trick is the incision of the flexor tendon at its insertion site. The site is protected by a shelf of bone which can make the incision on the flexor tendon too proximal. The skin incision is continued along the margin of the ventral claw and pad margin. The site is flushed with sterile saline. The extensor and flexor tendons are opposed with absorbable suture. This is important to keep the digit in a normal stance and not going flat footed. Then when the skin is closed, do not pull the cranial digital pad up to meet the dorsal aspect of the claw fold. This pulls the pad too far forward and may cause the patient to walk on the ventral interdigital haired skin creating a callus formation post-surgery. Bandages are changed 2-3 times a week as needed pending healing.

REFERENCES

1. Swaim SF, Lee AH, MacDonald JM, et al. Fusion for the treatment of chronic fibrosing interdigital pyoderma in the dog. J Am Anim Hosp Assoc 1991;27:264-74. 2. Papazoglou LG, Ellison GW, Farese JP et al. Fusion Podoplasty for the Management of Chronic Pedal Conditions in Seven Dogs and One Cat. J Am anim Hosp Assoc 2011;47:e199-e205 3. Duclos DD, Hargis AM, Hanley PW. Pathogenesis of canine interdigital palmar and plantar comedones and follicular cysts, and their response to laser surgery. Vet Derm 2008 19; 134-141 4. Liptak JM, Dernell WS, Rizzo SA, Withrow SJ. Partial Foot Amputation in 11 Dogs. J Am Anim Hosp Assoc 2005; 41:47-55. 5. Boord MJ, Griffin CE, Rosenkrantz WS. Onychectomy as a therapy for symmetric claw and claw fold disease in the dog. J Am Anim Hosp Assoc 1997; 33(2): 131-8.

® EFFICACY OF AFOXOLANDER (N EX GARD )

AGAINST CANINE MITES :

TREATMENT OF GENERALISED DEMODICOSIS

Fred Beugnet DVM PhD Dip EVPC, Merial S.A.S. Esther Rawlinson* BVMS MRCVS, Merial Animal Health UK

INTRODUCTION

Afoxolaner is an isoxazoline with insecticidal and acaricidal activity. Efficacy has been shown against fleas 1,2,3 and a range of tick species 1,4,5,6 . The purpose of this randomized, blinded, positive-controlled study was to assess the efficacy of oral administration of afoxolaner (NexGard ® chewable tablets) against mites for the treatment of naturally-occurring generalized demodicosis.

MATERIALS AND METHODS

Sixteen dogs (7 male, 9 female), aged over 6 months, weighing 4.5-15.1kg diagnosed with generalized demodicosis but otherwise healthy were recruited. Demodicosis was considered generalized if lesions affected more than 5 areas, an entire body area, or there was pododemodicosis involving two or more feet.

Dogs were ranked by pre-administration mite counts and then blocked into 8 blocks of 2 dogs each. Group 1 was administered a topical combination of imidacloprid/moxidectin (Advocate ®, Bayer) at the recommended dose rate and Group 2 received afoxolaner (NexGard ®, Merial) at the recommended dose of at least 2.5mg/kg. Treatments were administered on day 0, 14, 28 and 56.

According to the product label Advocate ® should be administered every 1-4 weeks for treatment of demodicosis. Based on pharmacokinetic properties of afoxolaner, initial 2-week treatment intervals were chosen in order to rapidly achieve steady state concentration in the blood. NexGard ® is labelled for monthly administration (against fleas and ticks) and previous studies have shown no adverse reactions in puppies administered 5 times the maximum dose on 6 occasions, including 3 treatments at 2 week intervals 1,2 .

Clinical examinations including deep skin scrapings were performed every 2 weeks for 3 months in order to evaluate the reduction in mite counts and the resolution of clinical signs. The extent of lesions: casts, scales and crusts; hair loss (graded 1-3), erythema, and an estimate of hair regrowth was recorded and drawn on a silhouette.

RESULTS:

The primary endpoint was the decrease in mite counts (immature and adult mites combined) and geometric means were used to compare the groups. Mite counts were compared by an ANOVA with level of significance set at p< 0.05.

The percentage reduction in Demodex mite counts on days 28, 56 and 84 was respectively 99.2%, 99.9%, and 100% in the afoxolaner-treated group versus 89.8%, 85.2%, and 86.6% in the imidacloprid/moxidectin-treated group (Table 1). Mite reduction was significantly higher at days 28, 56 and 84 in the afoxolaner-treated group.

Table 1 Group 1 (imidacloprid/moxidectin) Group 2 (afoxolaner) Day Geometric % p-value Geometric mean % reduction p-value mean mite reduction mite count count 0 808.1 650.8 28 82.4 89.8* 0.0008 5.3* 99.2* <.0001 56 119.9 85.2* 0.0038 0.6* 99.9* <.0001 84 108.5 86.6* 0.0025 0* 100* <.0001 * Group 2 differed statistically significantly (p<0.05) from group 1

The skin condition in both groups improved during the study. There was a reduction in the number of dogs with crusts: on day 84, 37.5% of Group 1 (3/8 dogs) and 25% of Group 2 dogs (2/8 dogs) still had crusts versus 75% (6/8) and 87.5% (7/8) respectively at the start of the study). A marked improvement in hair regrowth was observed in all dogs from week 8 onwards (Table 2). No treatment-related adverse events were observed during the study.

Table 2: Estimated percentage of hair re-growth Group 1 Day Group 2 (Afoxolaner) (Imidacloprid/moxidectin)

0-50% 50-90% >90% 0-50% 50-90% >90%

28 6/8 2/8 0/8 6/8 1/8 1/8

56 3/8 3/8 2/8 2/8 3/8 3/8

84 1/8 4/8 3/8 1/8 4/8 3/8

CONCLUSION

This study illustrates that afoxolaner (NexGard ®), given orally at 2 week intervals for one month and then after one month, was an effective treatment for dogs with generalised demodicosis, resulting in a rapid reduction in mite numbers and improvement in clinical signs.

REFERENCES

1. NexGardSPC. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_- _Product_Information/veterinary/002729/WC500164067.pdf 2. Dryden MW, Smith V, Chwala M, Jones E, Crevoiserat L, McGrady JC, Foley KM, Patton PR, Hawkins A and Carithers D. Evaluation of afoxolaner chewables to control flea populations in naturally infested dogs in private residences in Tampa FL, USA. Parasites & Vectors (2015) 8: 286 3. Kunkle BN, Drag MD, Chester TS and Larsen DL. Assessment of the onset of action of afoxolaner against existing adult flea ( Ctenocephalides felis ) infestations on dogs. Veterinary Parasitology (2014) 201 (3-4), 226-228 4. Dumont P, Blair J, Fourie JJ, Chester TS and Larsen DL Evaluation of the efficacy of afoxolaner against two European dog tick species: Dermacentor reticulatus and Ixodes ricinus . Veterinary Parasitology (2014) 201 (3-4) 216-219 5. Mitchell EB, McCall JW, Chester TS and Larsen DL. Efficacy of afoxolaner against Ixodes scapularis ticks in dogs. Veterinary Parasitology (2014) 201 (3-4) 223-225 6. Kunkle B, Daly S, Dumont P, Drag M and Larsen D. Assessment of the efficacy of orally administered afoxolaner against Rhipicephalus sanguineus sensu lato. Veterinary Parasitology (2014) 201 (3-4) 226-228 7. Drag M, Saik J, Harriman J and LarsenD. Safety evaluation of orally administered afoxolaner in 8-week-old dogs. Veterinary Parasitology (2014) 201, 198-203

CONFLICT OF INTEREST The study was funded by Merial SAS. Both authors are employed by Merial.

*Presenting author