Today's Veterinary Practice, January 2018

IN THIS ISSUE 28 INFLAMMATORY BOWEL DISEASE IN DOGS AND CATS 60 FLUID THERAPY IN HOSPITALIZED PATIENTS: PART 1 74 FOCUS ON LEPTOSPIROSIS

CE

Canine Atopic Dermatitis: Updates on Diagnosis and Treatment

JANUARY/FEBRUARY 2018 VOLUME 8, NUMBER 1

They already have a lot to remember.

Give them one less thing to forget.

No matter how busy life gets, at least you’ll know your patients are protected from fleas & ticks with BRAVECTO® Prescription-only BRAVECTO® provides up to 12 weeks* of extended protection against fleas & ticks with just one dose. Good for patients, good for compliance, good for your practice.

®

Ask your Merck Animal Health Rep about BRAVECTO® or Visit Bravectovets.com *BRAVECTO® kills fleas and prevents flea infestations for 12 weeks. BRAVECTO® Chew kills ticks (black-legged tick, American dog tick, and brown dog tick) for 12 weeks and also kills lone star ticks for 8 weeks.

Also available as a topical application.

Important Safety Information BRAVECTO Chews for Dogs: The most common adverse reactions recorded in clinical trials were vomiting, decreased appetite, diarrhea, lethargy, polydipsia, and flatulence.

Bravecto has not been shown to be effective for 12-weeks’ duration in puppies less than 6 months of age. Bravecto is not effective against lone star ticks beyond 8 weeks after dosing. See full Prescribing Information on page 7.

Copyright © 2018 Intervet Inc., d/b/a Merck Animal Health, a subsidiary of Merck & Co. Inc. All rights reserved. US/BRV/1117/0105

JANUARY/FEBRUARY 2018

VOLUME 8, NUMBER 1

An Official journal of the

An official journal of the NAVC, Today’s Veterinary Practice is the trusted source for peer-reviewed clinical information in small animal veterinary medicine. Our goal is to enhance knowledge and encourage confidence, inspiring the highest quality of veterinary care. As an NAVC publication, our audience has access to world-class continuing professional development developed for the global veterinary health care community.

Subscriptions (only): 630.739.0900, CDS/Today’s Veterinary Practice 440 Quadrangle Drive, Suite E, Bolingbrook, IL 60440. Email subscription form to subscriptions@CDS1976.com or fax to 630.739.9700 Free subscriptions only to qualifying subscribers.* For a new subscription, confirmation, or renewal, please visit tvpjournal.com to fill out an online form. For updates, please include your subscription ID from label. To have a form emailed or faxed to you, please contact us at our 800 number or email above and provide email or fax number.

Change Name/Address or Cancel: Please use online form at tvpjournal.com or contact us by phone, fax, or email subscriptions@CDS1976.com. Please provide the ID number (directly above your name on label) for positive identification. If the ID number is not available or legible, provide name and address as it appears on the label to allow identification of the subscription. *Qualifying Subscribers: Veterinarians, members of the veterinary health care team, veterinary school faculty, veterinary students, and other professionals allied to the field.

Eastern States Veterinary Association, Inc (NAVC) reserves the right to determine eligibility for a free subscription.

WARRANTIES, LIMITATIONS. Except as expressly set forth herein, Eastern States Veterinary Association, Inc (NAVC) makes no warranties whatsoever, express, implied, or statutory. NAVC specifically disclaims any implied warranty of merchantability or fitness for a particular purpose. In no event will NAVC be liable to you or any third party for any indirect, punitive, special, incidental, or consequential damages (including loss of profits, use, data, or other economic advantage), however it arises, even if NAVC has previously been advised of the possibility of such damage. All rights reserved. No part of this publication may be reproduced in any form without written permission from the publisher. Entire contents ©2017 Eastern States Veterinary Association, Inc (NAVC).

Editor in Chief Simon R. Platt, BVM&S, MRCVS, DACVIM (Neurology), DECVN University of Georgia College of Veterinary Medicine SRPlatt@NAVC.com

Chief Executive Officer, NAVC Thomas M. Bohn, MBA, CAE TBohn@NAVC.com

Laura C.S. Walker Chief Media Officer LWalker@NAVC.com Chris Kelly, Group Publisher CKelly@NAVC.com Rick Boggess, Vice President of Sales and Marketing, NAVC Publishing RBoggess@NAVC.com Nick Paolo, MS, MBA, Director of Operations and Finance, NAVC Publishing NPaolo@NAVC.com Jackie D’Antonio, Content Director JDantonio@NAVC.com Lillian McAnally, Managing Editor LMcAnally@NAVC.com Renee Luttrell, Director of Sales RLuttrell@NAVC.com, 610.558.1819

Editorial Advisory Board P. Jane Armstrong, DVM, MS, MBA, DACVIM, (Small Animal Internal Medicine) University of Minnesota, College of Veterinary Medicine

Paige Ellington, Account Executive PEllington@NAVC.com, 404.550.6649 Sondra Reynolds, Director of Audience Development SReynolds@NAVC.com Michelle Taylor, Senior Art Director David Beagin, Art Director and Designer Julie Butler, Assistant Editor

Mark Cofone, VMD, DACVS Veterinary Specialty Center, Wilmington, Delaware

Cheryl Hobbs, Staff Editor Suzanne B. Meyers, Staff Editor Lisa Wirth, VMD, Staff Editor

NAVC Board of Directors Sheila Grosdidier, RVT, PHR Veterinary Management Consultation Evergreen, Colorado

President Gail Gibson, VMD Immediate Past President Melinda D. Merck, DVM President-Elect K. Leann Kuebelbeck, DVM, DACVS

Garret Pachtinger, VMD, DACVECC Veterinary Specialty & Emergency Center Levittown, Pennsylvania Michael Schaer, DVM, DACVIM, DACVECC University of Florida College of Veterinary Medicine

Vice President Cheryl Good, DVM Treasurer Laurel Kaddatz, DVM Directors Paige Allen, MS, RVT Harold Davis, Jr, BA, RVT, VTS (Emergency & Critical Care) (Anesthesia & Analgesia) Sally Haddock, DVM Bob Lester, DVM Mark Russak, DVM

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JAN/FEB 2018

EDITOR’S NOTE

The Age of the Veterinary Nurse Has Arrived!

Simon R. Platts, BVM&S, MRCVS, DACVIM (Neurology), DECVN

96

FINDING BALANCE

Time Management Laura Baltodano

8 INSIDE NAVC 93 ADVERTISER INDEX

14

ESSENTIALS

PRACTICAL PARASITOLOGY

Heartworm Infection in Ferrets Leonie Kondert, DVM; and Joerg Mayer, DVM, MS, DABVP, DACZM

This article discusses the clinical signs and diagnostics, treatment and preventative medicine for heartworm infection in ferrets.

18

NUTRITION NOTES

Diarrhea, Vomiting, and Food, Oh My! Nutritional Management for Gastrointestinal Disease Angela Witzel, DVM, PhD, DACVN

22

FROM THE FIELD

Focus on Overweight and Obesity in Cats Kirk Breuninger, VMD, MPH, DACVPM

Today’s Veterinary Practice does not, by publication of ads, express endorsement or verify the accuracy and effectiveness of the products and claims contained therein. The publisher, Eastern States Veterinary Association, Inc (NAVC), disclaims any liability for any damages resulting from the use of any product advertised herein and suggests that readers fully investigate the products and claims prior to purchasing. The opinions stated in this publication are those of the respective authors and do not necessarily represent the opinions of the NAVC nor its Editorial Advisory Board. NAVC does not guarantee nor make any other representation that the material contained in articles herein is valid, reliable, or accurate; nor does the NAVC assume any responsibility for injury or death arising from any use, or misuse, of same. There is no implication that the material published herein represents the best or only procedure for a particular condition. It is the responsibility of the reader to verify the accuracy and applicability of any information presented and to adapt as new data becomes publicly available. Today’s Veterinary Practice (ISSN 2162-3872 print and ISSN 2162-3929 online) is published bi-monthly (Jan/Feb, Mar/Apr, May/June, Jul/Aug, Sept/Oct, Nov/Dec; 6x per year) by North American Veterinary Community, NAVC, 622 East Washington St, Ste 300, Orlando, FL 32801. Periodicals postage paid at Orlando, FL 32801 and additional mailing offices. POSTMASTER: Send all UAA to CFS (See DMM 507.1.5.2); NON-POSTAL AND MILITARY FACILITIES: send address corrections to CDS/Today’s Veterinary Practice, 440 Quadrangle Drive, Ste E, Bolingbrook, IL 60440.

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TABLE OF CONTENTS

To read this issue online, visit tvpjournal.com

A Strength for Every Dog AVAILABLE IN 5 MG, 10 MG, 30 MG, 60 MG AND 120 MG CAPSULES

Come learn how to diagnose and treat Cushing’s disease in Dechra Academy • 2 Separate Modules – Learn at your own pace • Free – Just sign up or use your existing Dechra login • RACE Approved

www.dechra-us.com/CE VETORYL Capsules offers a full range of sizes from 5 mg up to 120 mg, so you don’t have to rely on compounders to provide the dose that’s right for the patient, regardless of how small or how large.

VETORYL Capsules are the only FDA veterinary-approved treatment for pituitary-dependent and adrenaldependent hyperadrenocorticism in dogs (Cushing’s syndrome). They contain the active ingredient trilostane, which blocks the excessive production of cortisol.

As with all drugs, side effects may occur. In field studies and post-approval experience, the most common side effects reported were: anorexia, lethargy/depression, vomiting, diarrhea, elevated liver enzymes, elevated potassium with or without elevated sodium, elevated BUN, decreased Na/K ratio, hypoadrenocorticism, weakness, elevated creatinine, shaking, and renal insufficiency. In some cases, death has been reported as an outcome of these adverse events. VETORYL Capsules are not for use in dogs with primary hepatic or renal disease, or in pregnant dogs. Refer to the prescribing information for complete details or visit www.Dechra-US.com.

24 Hour Technical Support:

866-933-2472 | www.dechra-us.com | support@dechra.com

NADA 141-291, Approved by FDA CAUTION: Federal law restricts this drug to use by or on the order of licensed veterinarian.

1 http://www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/FOIADrugSummaries/ucm049823.htm Vetoryl is a registered trademark of Dechra Limited. Dechra is a registered trademark of Dechra Pharmaceuticals PLC. ©2015, Dechra Ltd

28

FEATURES CONTINUING EDUCATION

Inflammatory Bowel Disease in Dogs and Cats Kayode Garraway, DVM; Karin Allenspach, DVM, PhD, DECVIM-CA; and Albert Jergens, DVM, MS, PhD, DACVIM (SAIM)

This article provides an overview of the factors involved in canine and feline IBD, including the genetic, immune, environmental, and gastrointestinal interactions, as well as clinical findings, diagnosis, treatment options, and prognosis.

42

CONTINUING EDUCATION

Canine Atopic Dermatitis: Updates on Diagnosis and Treatment

60

FLUID THERAPY: PART 1

Gastric Dilation and Volvulus: Stabilization and Surgery Bridget M. Lyons, VMD; and Lori S. Waddell, DVM, DACVECC

Frane Banovic, DVM, PhD, DECVD

This article discusses the pathogenesis, diagnosis, and management of canine atopic dermatitis.

This article reviews fluid distribution, assessment of hydration, types of body fluid losses, types of fluids available, and calculation of fluid needs.

74

CLINICAL INSIGHTS FOCUS ON

Leptospirosis Madeline Fujishiro, DVM; and Kate E. Creevy, DVM, MS, DACVIM

This article discusses the physical examination and diagnostics, initial therapy, diagnosis, and treatment of Leptospirosis. The presenting is a 1-year-old, castrated male dachshund with an acute onset of lethargy, anorexia, and vomiting.

82 IMAGING ESSENTIALS

Ultrasonography of the Gastrointestinal Tract: Stomach, Duodenum, and Jejunum Elizabeth Huyhn, DVM; and Clifford R. Berry, DVM, DACVR

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TABLE OF CONTENTS

To read this issue online, visit tvpjournal.com

SEE MORE

THAN WHAT’S ON THE SURFACE. DIAGNOSE BELOW THE GUM LINE WITH SCHICK 33 With more pet owners demanding high-quality veterinary dental care, it makes sense to add the Dentsply Sirona digital x-ray system with Schick 33 and Heliodent Plus to your practice. Together these products provide an easy solution for high-resolution intraoral radiography and the best diagnostic capabilities. Contact your Veterinary sales representative or learn more at vet.schickbysirona.com

EDITOR’S NOTE

Simon R. Platt, BVM&S, MRCVS, DACVIM (Neurology), DECVN University of Georgia

EDITOR’S NOTE

The Age of the Veterinary Nurse Has Arrived!

Part I: What’s in a Name?

“ I am of certain convinced that the greatest heroes are those who do their duty in the daily grind of domestic affairs whilst the world whirls as a maddening dreidel.” 1

— Florence Nightingale

If anything prevents continued advancement of this professional body, it may be the confusion over why there are so many different titles. If this confuses us, then how does it affect our patients’ owners’ acceptance and recognition, an integral component in improving our retention of veterinary technicians?

I will focus on where we are, and the next editorial will focus on where the veterinary nursing profession may be headed in the next decade.

Currently, veterinary technicians, one of the most well-known designations, have credentials, which vary between states. A credentialed veterinary technician may be registered (RVT), licensed (LVT), certified (CVT) or a licensed veterinary medical technician (LVMT)!

An interesting map of the state-by-state credentialing terminology is available on the National Association of Veterinary Technicians in America (NAVTA) website.2 Veterinary technicians are required to attend and graduate from an AVMA-approved (American Veterinary Medical Association) program and pass the Veterinary Technician National Examination. State dependent, there may also be additional examinations and CE requirements, bi-annual https://www.goodreads.com/quotes/63084-i-am-of-certain-convincedthat-the-greatest-heroes-are (accessed November 20, 2017).

For detail by state, visit: http://www.navta.net/resource/resmgr/vn_ initiative/VeterinaryNursingMap.html

1

2

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EDITOR’S NOTE

or annual. At the time of this writing, a veterinary assistant is defined as an individual who provides care under the supervision of a veterinarian or credentialed veterinary technician, and designated as either approved (AVA) or certified (CVA), based on whether NAVTA or the state veterinary medical association oversees their training. Further to this, a veterinary technician specialist (VTS) designation can be achieved by a credentialed veterinary technician with extra training in one of NAVTA-recognized 15 academies, which include ophthalmology, surgery and internal medicine.

To many people, these credentials can be confusing and, understandably, lead to a lack of recognition of the individuals working alongside us and the amount of work they invested to get to that point. This is obviously aside from the possibility that this confusion may also lead to a lack of financial reward, which should, ideally, mirror the person’s qualification and experience.

In 2017, NAVTA announced its plans to move forward with the veterinary nurse credential change with the formation of the Veterinary Nurse Initiative (VNI) Coalition. Pursuing legislative changes in all 50 states to establish the credential of registered veterinary nurse, NAVTA’s board approved the action replace the titles of RVT, LVT, CVT and LVMT, and unite the profession under a single title, set of credentialing requirements, and scope of practice. Although a challenging and time-consuming process, it’s one that will help to unify the profession and create a platform for the continued advancement and integration of veterinary nursing into our practices, whatever geographic and socio-economic society they serve.

As veterinarians, we should ensure this wait for a new name does not deter us with respect to constantly improving the integration of nurses into the ever-changing face of our practices, achieving more efficiency, better patient care, improved client confidence, and most importantly, long-term retention of these invaluable professionals.

NADA 141-426, Approved by FDA

Flavored chews for dogs.

BRIEF SUMMARY (For full Prescribing Information, see package insert) Caution: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Indications: Bravecto kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), and Rhipicephalus sanguineus (brown dog tick)] for 12 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.

Bravecto is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for 8 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.

Contraindications: There are no known contraindications for the use of the product.

Warnings: Not for human use. Keep this and all drugs out of the reach of children. Keep the product in the original packaging until use, in order to prevent children from getting direct access to the product. Do not eat, drink or smoke while handling the product.

Wash hands thoroughly with soap and water immediately after use of the product.

Precautions: Bravecto has not been shown to be effective for 12-weeks duration in puppies less than 6 months of age. Bravecto is not effective against Amblyomma americanum ticks beyond 8 weeks after dosing.

Adverse Reactions: In a well-controlled U.S. field study, which included 294 dogs (224 dogs were administered Bravecto every 12 weeks and 70 dogs were administered an oral active control every 4 weeks and were provided with a tick collar); there were no serious adverse reactions. All potential adverse reactions were recorded in dogs treated with Bravecto over a 182-day period and in dogs treated with the active control over an 84-day period. The most frequently reported adverse reaction in dogs in the Bravecto and active control groups was vomiting.

NADA 141-459, Approved by FDA

NADA 141-459, Approved by FDA

(fluralaner topical solution) for Dogs

(fluralaner topical solution) for Cats

BRIEF SUMMARY (For full Prescribing Information, see package insert)

BRIEF SUMMARY (For full Prescribing Information, see package insert)

Caution: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Caution: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Indications: Bravecto kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of tick infestations [Ixodes scapularis (black-legged tick), Dermacentor variabilis (American dog tick), and Rhipicephalus sanguineus (brown dog tick)] for 12 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.

Bravecto is also indicated for the treatment and control of Amblyomma americanum (lone star tick) infestations for 8 weeks in dogs and puppies 6 months of age and older, and weighing 4.4 pounds or greater.

Contraindications: There are no known contraindications for the use of the product.

WARNINGS Human Warnings: Not for human use. Keep this and all drugs out of the reach of children. Do not contact or allow children to contact the application site until dry.

Keep the product in the original packaging until use in order to prevent children from getting direct access to the product. Do not eat, drink or smoke while handling the product. Avoid contact with skin and eyes. If contact with eyes occurs, then flush eyes slowly and gently with water. Wash hands and contacted skin thoroughly with soap and water immediately after use of the product.

The product is highly flammable. Keep away from heat, sparks, open flame or other sources of ignition.

Precautions: For topical use only. Avoid oral ingestion. Use with caution in dogs with a history of seizures. Seizures have been reported in dogs receiving fluralaner, even in dogs without a history of seizures. Bravecto has not been shown to be effective for 12-weeks duration in puppies less than 6 months of age. Bravecto is not effective against Amblyomma americanum ticks beyond 8 weeks after dosing.

Adverse Reactions: In a well-controlled U.S. field study, which included a total of 165 households and 321 treated dogs (221 with fluralaner and 100 with a topical active control), there were no serious adverse reactions.

Percentage of Dogs with Adverse Reactions in the Field Study

Percentage of Dogs with Adverse Reactions in the Field Study Adverse Reaction (AR) Vomiting Decreased Appetite Diarrhea Lethargy Polydipsia Flatulence

Bravecto Group: Active Control Group: Percentage of Dogs Percentage of Dogs with the AR During the with the AR During 182-Day Study the 84-Day Study (n=224 dogs) (n=70 dogs) 7.1 14.3 6.7 0.0 4.9 2.9 5.4 7.1 1.8 4.3 1.3 0.0

In a well-controlled laboratory dose confirmation study, one dog developed edema and hyperemia of the upper lips within one hour of receiving Bravecto. The edema improved progressively through the day and had resolved without medical intervention by the next morning.

For technical assistance or to report a suspected adverse drug reaction, contact Merck Animal Health at 1-800-224-5318. Additional information can be found at www. bravecto.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/ AnimalVeterinary/ SafetyHealth.

How Supplied: Bravecto is available in five strengths (112.5, 250, 500, 1000, and 1400 mg fluralaner per chew). Each chew is packaged individually into aluminum foil blister packs sealed with a peelable paper backed foil lid stock. Product may be packaged in 1, 2, or 4 chews per package.

Distributed by: Intervet Inc (d/b/a Merck Animal Health) Madison, NJ 07940 Made in Austria Copyright © 2014 Intervet Inc, a subsidiary of Merck & Company Inc. All rights reserved 154545 R1

Adverse Reaction (AR) Vomiting Alopecia Diarrhea Lethargy Decreased Appetite Moist Dermatitis/Rash

Bravecto Group: Percent of Dogs with the AR During the 105-Day Study (n=221 dogs) 6.3% 4.1% 2.7% 2.7% 1.4% 0.9%

Control Group: Percent of Dogs with the AR During the 84-Day Study (n=100 dogs) 6.0% 2.0% 11.0% 2.0% 0.0% 0.0%

In the field study, two dogs treated with Bravecto with no prior history of seizures each experienced a seizure. One dog had two seizures a day apart about 18 days after its first dose. The dog was started on antiepileptic medication and had no additional seizures during the study. A second dog had a seizure 76 days after its first dose and 3 days after starting fluoxetine for separation anxiety. The fluoxetine was discontinued and the dog experienced no additional seizures during the study. One dog treated with Bravecto was observed by the owner to be off balance for about 30 minutes five days after its first dose and had no similar observations after the second dose. One dog with a history of seizures had a seizure the day after the second dose of the active control.

In two well-controlled laboratory dose confirmation studies, one dog developed mild to moderate redness, flaking, crusts/scabs and alopecia at the treatment site from Day 1 through 14 after application of Bravecto on Day 0, and one dog developed self-limiting generalized erythema (possible allergic reaction) one day after treatment with Bravecto.

Indications: Bravecto kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis) and the treatment and control of Ixodes scapularis (black-legged tick) infestations for 12 weeks in cats and kittens 6 months of age and older, and weighing 2.6 pounds or greater.

Bravecto is also indicated for the treatment and control of Dermacentor variabilis (American dog tick) infestations for 8 weeks in cats and kittens 6 months of age and older, and weighing 2.6 pounds or greater.

Contraindications: There are no known contraindications for the use of the product.

WARNINGS Human Warnings: Not for human use. Keep this and all drugs out of the reach of children. Do not contact or allow children to contact the application site until dry.

Keep the product in the original packaging until use in order to prevent children from getting direct access to the product. Do not eat, drink or smoke while handling the product. Avoid contact with skin and eyes. If contact with eyes occurs, then flush eyes slowly and gently with water. Wash hands and contacted skin thoroughly with soap and water immediately after use of the product.

The product is highly flammable. Keep away from heat, sparks, open flame or other sources of ignition.

Precautions: For topical use only. Avoid oral ingestion. Use with caution in cats with a history of neurologic abnormalities. Neurologic abnormalities have been reported in cats receiving Bravecto, even in cats without a history of neurologic abnormalities.

Bravecto has not been shown to be effective for 12-weeks duration in kittens less than 6 months of age. Bravecto is not effective against Dermacentor variabilis ticks beyond 8 weeks after dosing. The safety of Bravecto has not been established in breeding, pregnant and lactating cats.

Adverse Reactions: In a well-controlled U.S. field study, which included a total of 161 households and 311 treated cats (224 with fluralaner and 87 with a topical active control), there were no serious adverse reactions.

Percentage of Cats with Adverse Reactions (AR) in the Field Study Adverse Reaction (AR)

Bravecto Group: Percent of Cats with the AR During the 105Day Study (n=224 cats)

Vomiting Pruritus Diarrhea Alopecia Decreased Appetite Lethargy Scabs/Ulcerated Lesions

7.6% 5.4% 4.9% 4.9% 3.6% 3.1% 2.2%

Control Group: Percent of Cats with the AR During the 84-Day Study (n=87 cats) 6.9% 11.5% 1.1% 4.6% 0.0% 2.3% 3.4%

In the field study, two cats treated with fluralaner topical solution experienced ataxia.

One cat became ataxic with a right head tilt 34 days after the first dose. The cat improved within one week of starting antibiotics. The ataxia and right head tilt, along with lateral recumbency, reoccurred 82 days after administration of the first dose.

The cat recovered with antibiotics and was redosed with fluralaner topical solution 92 days after administration of the first dose, with no further abnormalities during the study. A second cat became ataxic 15 days after receiving its first dose and recovered the next day. The cat was redosed with fluralaner topical solution 82 days after administration of the first dose, with no further abnormalities during the study.

In a European field study, two cats from the same household experienced tremors, lethargy, and anorexia within one day of administration. The signs resolved in both cats within 48-72 hours.

In a European field study in cats, there were three reports of facial dermatitis in humans after close contact with the application site which occurred within 4 days of application.

In a European field study, there were three reports of facial dermatitis in humans after close contact with the application site which occurred within 4 days of application.

For technical assistance or to report a suspected adverse drug reaction, or to obtain a copy of the Safety Data Sheet (SDS), contact Merck Animal Health at 1-800-224-5318. Additional information can be found at www.bravecto.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth.

For technical assistance or to report a suspected adverse drug reaction, or to obtain a copy of the Safety Data Sheet (SDS), contact Merck Animal Health at 1-800-224-5318.

Additional information can be found at www.bravecto.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDAVETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth.

How Supplied: Bravecto is available in five strengths for use in dogs (112.5, 250, 500, 1000, and 1400 mg fluralaner per tube). Each tube is packaged individually in a pouch. Product may be supplied in 1 or 2 tubes per carton.

How Supplied: Bravecto is available in three strengths for use in cats (112.5, 250, and 500 mg fluralaner per tube). Each tube is packaged individually in a pouch. Product may be supplied in 1 or 2 tubes per carton.

Distributed by: Intervet Inc (d/b/a Merck Animal Health) Madison, NJ 07940 Made in the USA.

Distributed by: Intervet Inc (d/b/a Merck Animal Health) Madison, NJ 07940 Made in the USA.

Rev. 9/16

Rev. 9/16

Copyright © 2016 Intervet Inc, a subsidiary of Merck & Company Inc. All rights reserved

Copyright © 2016 Intervet Inc, a subsidiary of Merck & Company Inc. All rights reserved

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INSIDE NAVC

WHAT NOT TO MISS AT VMX 2018 This year, VMX 2018, formerly the NAVC Conference, is bigger and better than ever. As always, it will feature top-tier continuing education opportunities from world-renowned presenters, but VMX 2018 is much more than that.

From unparalleled professional development and networking opportunities to exciting entertainment events, there is so much more to discover. Take full advantage of your VMX experience by hitting all of these exciting events.

General Session This year’s General Session welcomes award-winning actor, author and Parkinson’s Disease advocate, Michael J. Fox. With his characteristic wit and charm, come listen to him share his life experiences in “A Funny Thing Happened on the Way to the Future” as he makes the case that real learning and growth actually happens when life goes skidding sideways. The General Session will take place on Saturday, February 3, at 10:30 am at the Hilton Orlando and is open to all attendees.

Opening Ceremony Kicking off Day 1 is renowned Conservationist and Environmental Journalist, Jeff Corwin, leading the Opening Ceremony presented by Hill’s Pet Nutrition.

The host of “Ocean Mysteries” will share his one-of-akind perspective on wildlife conservation and empower VMX attendees to join the movement to save the natural world for future generations. The event will take place Saturday, February 3, at 7:00 pm at the Hilton Orlando.

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INSIDE NAVC

Learning Theater and Campus Theater While you are visiting booths inside the VMX Expo Hall, be sure to catch some of our CE offerings, brought to you by our Industry Partners, available in both our Learning Theater and Campus Theater settings. These CE sessions will be available for attendees during Expo Hall hours, starting Sunday, February 4 through Wednesday, February 7.

The Learning Theater will be located inside NAVC Central inside the Expo Hall. CE sessions last about 45 minutes, featuring current topics that impact veterinary practices and veterinary professionals.

INSIDE NAVC

The Campus Theater will be located in the Education Square inside the Expo Hall. The content for these CE sessions will be similar to content presented in a traditional symposia session, but will be delivered in a more relaxed setting and generally last about 105 minutes.

VETORYL® CAPSULES (trilostane)

5 mg, 10 mg, 30 mg, 60 mg and 120 mg strengths Adrenocortical suppressant for oral use in dogs only.

BRIEF SUMMARY (For Full Prescribing Information, see package insert.)

Be sure to check out the daily VMX newspaper, INSIDE VMX, to review the schedule and session details for the Learning Theater and Campus Theater, including topics, speakers and fun giveaways provided by our sponsors!

CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

DESCRIPTION: VETORYL Capsules are an orally active synthetic steroid analogue that blocks production of hormones produced in the adrenal cortex of dogs.

Hands-on Laboratories and Rounds

INDICATION: VETORYL Capsules are indicated for the treatment of pituitary- and adrenal-dependent hyperadrenocorticism in dogs.

Perfecting today’s specialized procedures takes practice, and you’ll get plenty of that at VMX 2018. Choose from over 30 Hands-on Laboratories led by seasoned instructors and all the tools, supplies and space needed to practice.

CONTRAINDICATIONS: The use of VETORYL Capsules is contraindicated in dogs that have demonstrated hypersensitivity to trilostane. Do not use VETORYL Capsules in animals with primary hepatic disease or renal insufficiency. Do not use in pregnant dogs. Studies conducted with trilostane in laboratory animals have shown teratogenic effects and early pregnancy loss.

In addition, VMX 2018 provides the opportunity to explore challenging, real cases with Rounds. In these 2-hour sessions, join top practitioners as they share how they managed their most unusual or challenging cases.

WARNINGS: In case of overdosage, symptomatic treatment of hypoadrenocorticism with corticosteroids, mineralocorticoids and intravenous fluids may be required. Angiotensin converting enzyme (ACE) inhibitors should be used with caution with VETORYL Capsules, as both drugs have aldosterone-lowering effects which may be additive, impairing the patient’s ability to maintain normal electrolytes, blood volume and renal perfusion.

Potassium sparing diuretics (e.g. spironolactone) should not be used with VETORYL Capsules as both drugs have the potential to inhibit aldosterone, increasing the likelihood of hyperkalemia.

Register in advance for these unique opportunities, or upon your arrival at VMX 2018, head to Registration at the Orange County Convention Center or the Registration Center at the Hilton Orlando, to sign up for any remaining available spots.

Run with Your Pet Get ready to run at the 5k Fun(d) Run/Walk on February 4 at 7:00 am. Bring your pet or run with an adoptable shelter dog! Join the NAVC, IDEXX, the WSAVA Foundation, Pet Rescue by Judy and the K9 Kit Club at Bill Frederick Park at Turkey Lake for this event for a great cause. The cost is $35 per person, pets run free.

HUMAN WARNINGS: Keep out of reach of children.

Not for human use. Wash hands after use. Do not empty capsule contents and do not attempt to divide the capsules. Do not handle the capsules if pregnant or if trying to conceive. Trilostane is associated with teratogenic effects and early pregnancy loss in laboratory animals. In the event of accidental ingestion/overdose, seek medical advice immediately and take the labeled container with you.

Sunday “Big Game” Event Calling all sports fans! Join us Sunday, February 4, at 5:30 pm at the Hilton Orlando for a viewing party of Super Bowl LII and watch the two final teams face off for the championship.

PRECAUTIONS: Hypoadrenocorticism can develop at any dose of VETORYL Capsules. A small percentage of dogs may develop corticosteroid withdrawal syndrome within 10 days of starting treatment. Mitotane (o,p’-DDD) treatment will reduce adrenal function. Experience in foreign markets suggests that when mitotane therapy is stopped, an interval of at least one month should elapse before the introduction of VETORYL Capsules. The use of VETORYL Capsules will not affect the adrenal tumor itself. Adrenalectomy should be considered as an option for cases that are good surgical candidates.

The safe use of this drug has not been evaluated in lactating dogs and males intended for breeding.

VMX Concert Series Presents: Rob Thomas Join us for electrifying VMX concert entertainment with one of modern music’s most compelling artists, Matchbox Twenty’s, Rob Thomas. Aside from his award-winning music career, Thomas is also an avid animal lover, pet owner and supporter of animal charities. Thomas will take the stage on Monday, February 5, at 8:00 pm at the Hilton Orlando.

ADVERSE REACTIONS: The most common adverse reactions reported are poor/reduced appetite, vomiting, lethargy/dullness, diarrhea, elevated liver enzymes, elevated potassium with or without elevated sodium, elevated BUN, decreased Na/K ratio, weakness, elevated creatinine, shaking, and renal insufficiency. Occasionally, more serious reactions, including severe depression, hemorrhagic diarrhea, collapse, hypoadrenocortical crisis or adrenal necrosis/rupture may occur, and may result in death.

Distributed by: Dechra Veterinary Products 7015 College Boulevard, Suite 525 Overland Park, KS 66211 VETORYL is a trademark of Dechra Ltd. © 2015, Dechra Ltd. NADA 141-291, Approved by FDA

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TM

(sarolaner) Chewables

FOR ORAL USE IN DOGS ONLY CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Description: SIMPARICA is a flavored, chewable tablet for administration to dogs over 6 months of age according to their weight. Each tablet is formulated to provide a minimum sarolaner dosage of 0.91 mg/lb (2 mg/kg) body weight.

Sarolaner is a member of the isoxazoline class of parasiticides and the chemical name is 1-(5’-((5S)-5-(3,5-Dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3’H-spiro(azetidine-3,1’-(2)benzofuran)-1-yl)-2-(methylsulfonyl)ethanone. SIMPARICA contains the S-enantiomer of sarolaner.

The chemical structure of the S-enantiomer of sarolaner is: F F

F O

N

O

CI

F

CI N

O O

S O

Indications: SIMPARICA kills adult fleas, and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis), and the treatment and control of tick infestations [Amblyomma americanum (lone star tick), Amblyomma maculatum (Gulf Coast tick), Dermacentor variabilis (American dog tick), Ixodes scapularis (black-legged tick), and Rhipicephalus sanguineus (brown dog tick)] for one month in dogs 6 months of age or older and weighing 2.8 pounds or greater.

Dosage and Administration: SIMPARICA is given orally once a month at the recommended minimum dosage of 0.91 mg/lb (2 mg/kg).

Dosage Schedule: Body Weight SAROLANER per Tablet (mg) Number of Tablets Administered 2.8 to 5.5 lbs 5 One 5.6 to 11.0 lbs 10 One 11.1 to 22.0 lbs 20 One 22.1 to 44.0 lbs 40 One 44.1 to 88.0 lbs 80 One 88.1 to 132.0 lbs 120 One >132.1 lbs Administer the appropriate combination of tablets SIMPARICA can be offered by hand, in the food, or administered like other tablet medications.

Care should be taken that the dog consumes the complete dose, and treated animals should be observed for a few minutes to ensure that part of the dose is not lost or refused. If a dose is missed, administer SIMPARICA and resume a monthly dosing schedule.

SIMPARICA should be administered at monthly intervals.

Flea Treatment and Prevention: Treatment with SIMPARICA may begin at any time of the year. In areas where fleas are common year-round, monthly treatment with SIMPARICA can continue the entire year without interruption.

To minimize the likelihood of flea re-infestation, it is important to treat all dogs and cats within a household with an approved flea control product.

Tick Treatment and Control: Treatment with SIMPARICA can begin at any time of the year (see Effectiveness).

Contraindications: There are no known contraindications for the use of SIMPARICA. Warnings: Not for use in humans. Keep this and all drugs out of reach of children and pets. For use in dogs only. Do not use SIMPARICA in cats.

SIMPARICA should not be used in dogs less than 6 months of age (see Animal Safety).

Precautions: SIMPARICA may cause abnormal neurologic signs such as tremors, decreased conscious proprioception, ataxia, decreased or absent menace, and/or seizures (see Animal Safety).

The safe use of SIMPARICA has not been evaluated in breeding, pregnant, or lactating dogs.

Adverse Reactions: SIMPARICA was administered in a well-controlled US field study, which included a total of 479 dogs (315 dogs treated with SIMPARICA and 164 dogs treated with active control once monthly for three treatments).

Over the 90-day study period, all observations of potential adverse reactions were recorded.

Table 1. Dogs with adverse reactions Adverse reaction sarolaner sarolaner active control active control N % (n = 315) N % (n =164) Vomiting 3 0.95% 9 5.50% Diarrhea 2 0.63% 2 1.20% Lethargy 1 0.32% 2 1.20% Inappetence 0 0% 3 1.80%

Additionally, one female dog aged 8.6 years exhibited lethargy, ataxia while posturing to eliminate, elevated third eyelids, and inappetence one day after receiving SIMPARICA concurrently with a heartworm preventative (ivermectin/pyrantel pamoate). The signs resolved one day later. After the day 14 visit, the owner elected to withdraw the dog from the study.

For a copy of the Safety Data Sheet (SDS) or to report adverse reactions call Zoetis Inc. at 1-888-963-8471. Additional information can be found at www.SIMPARICA.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/AnimalVeterinary/SafetyHealth.

Clinical Pharmacology: Sarolaner is rapidly and well absorbed following oral administration of SIMPARICA. In a study of 12 Beagle dogs the mean maximum plasma concentration (Cmax) was 1100 ng/mL and the mean time to maximum concentration (Tmax) occurred at 3 hours following a single oral dose of 2 mg/kg to fasted animals. The mean oral bioavailability was 86% and 107% in fasted and fed dogs, respectively. The mean oral T1/2 values for fasted and fed animals was 10 and 12 days respectively.

Sarolaner is distributed widely; the mean volume of distribution (Vdss) was 2.81 L/kg bodyweight following a 2 mg/kg intravenous dose of sarolaner. Sarolaner is highly bound (≥99.9%) to plasma proteins. The metabolism of sarolaner appears to be minimal in the dog.

The primary route of sarolaner elimination from dogs is biliary excretion with elimination via the feces.

Following repeat administration of SIMPARICA once every 28 days for 10 doses to Beagle dogs at 1X, 3X, and 5X the maximum intended clinical dose of 4 mg/kg, steady-state plasma concentrations were reached after the 6th dose. Following treatment at 1X, 3X, and 5X the maximum intended clinical dose of 4 mg/kg, sarolaner systemic exposure was dose proportional over the range 1X to 5X. Mode of Action: The active substance of SIMPARICA, sarolaner, is an acaricide and insecticide belonging to the isoxazoline group. Sarolaner inhibits the function of the neurotransmitter gamma aminobutyric acid (GABA) receptor and glutamate receptor, and works at the neuromuscular junction in insects. This results in uncontrolled neuromuscular activity leading to death in insects or acarines.

Effectiveness: In a well-controlled laboratory study, SIMPARICA began to kill fleas 3 hours after initial administration and reduced the number of live fleas by ≥96.2% within 8 hours after flea infestation through Day 35.

In a separate well-controlled laboratory study, SIMPARICA demonstrated 100% effectiveness against adult fleas within 24 hours following treatment and maintained 100% effectiveness against weekly re-infestations for 35 days.

In a study to explore flea egg production and viability, SIMPARICA killed fleas before they could lay eggs for 35 days. In a study to simulate a flea-infested home environment, with flea infestations established prior to the start of treatment and re-infestations on Days 7, 37 and 67, SIMPARICA administered monthly for three months demonstrated >95.6% reduction in adult fleas within 14 days after treatment and reached 100% on Day 60.

In well-controlled laboratory studies, SIMPARICA demonstrated ≥99% effectiveness against an initial infestation of Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis, and Rhipicephalus sanguineus 48 hours post-administration and maintained >96% effectiveness 48 hours post re-infestation for 30 days.

In a well-controlled 90-day US field study conducted in households with existing flea infestations of varying severity, the effectiveness of SIMPARICA against fleas on Day 30, 60 and 90 visits compared to baseline was 99.4%, 99.8%, and 100%, respectively. Dogs with signs of flea allergy dermatitis showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis and pruritus as a direct result of eliminating fleas.

Animal Safety: In a margin of safety study, SIMPARICA was administered orally to 8-week-old Beagle puppies at doses of 0, 1X, 3X, and 5X the maximum recommended dose (4 mg/kg) at 28-day intervals for 10 doses (8 dogs per group). The control group received placebo tablets. No neurologic signs were observed in the 1X group. In the 3X group, one male dog exhibited tremors and ataxia post-dose on Day 0; one female dog exhibited tremors on Days 1, 2, 3, and 5; and one female dog exhibited tremors on Day 1. In the 5X group, one female dog had a seizure on Day 61 (5 days after third dose); one female dog had tremors post-dose on Day 0 and abnormal head coordination after dosing on Day 140; and one female dog exhibited seizures associated with the second and fourth doses and tremors associated with the second and third doses. All dogs recovered without treatment. Except for the observation of abnormal head coordination in one dog in the 5X group two hours after dosing on Day 140 (dose 6). There were no treatment-related neurological signs observed once the dogs reached the age of 6 months.

In a separate exploratory pharmacokinetic study, one female dog dosed at 12 mg/kg (3X the maximum recommended dose) exhibited lethargy, anorexia, and multiple neurological signs including ataxia, tremors, disorientation, hypersalivation, diminished proprioception, and absent menace, approximately 2 days after a third monthly dose. The dog was not treated, and was ultimately euthanized. The first two doses resulted in plasma concentrations that were consistent with those of the other dogs in the treatment group. Starting at 7 hours after the third dose, there was a rapid 2.5 fold increase in plasma concentrations within 41 hours, resulting in a Cmax more than 7-fold higher than the mean Cmax at the maximum recommended use dose.

No cause for the sudden increase in sarolaner plasma concentrations was identified.

Storage Information: Store at or below 30°C (86°F) with excursions permitted up to 40°C (104°F).

How Supplied: SIMPARICA (sarolaner) Chewables are available in six flavored tablet sizes: 5, 10, 20, 40, 80, and 120 mg. Each tablet size is available in color-coded packages of one, three, or six tablets.

NADA #141-452, Approved by FDA Distributed by: Zoetis Inc. Kalamazoo, MI 49007 Made in Switzerland

Revised: July 2016

50070900A&P

NOT ALL FLEA AND TICK CHEWS ARE CREATED EQUAL

Flea and tick protection that goes on and on and on...all month long

Recommend Simparica to your clients Simparica acts fast—it starts killing fleas within 3 hours and ticks within 8 hours*—and keeps going strong for 35 days* without losing effectiveness at the end of the month.

Premium protection without the premium price— with our rebate offers and affordable price, you can compete against OTC brands and bring flea and tick protection back into your practice.

IMPORTANT SAFETY INFORMATION: Simparica is for use only in dogs, 6 months of age and older.

Simparica may cause abnormal neurologic signs such as tremors, decreased conscious proprioception, ataxia, decreased or absent menace, and/or seizures. Simparica has not been evaluated in dogs that are pregnant, breeding or lactating. Simparica has been safely used in dogs treated with commonly prescribed vaccines, parasiticides and other medications. The most frequently reported adverse reactions were vomiting and diarrhea. See full Prescribing Information on the back of this page and at www.zoetisUS.com/SimparicaPI. *Studies show Simparica starts killing ticks in 8 hours and is ≥96.9% effective for 35 days against weekly reinfestations of Ixodes scapularis, Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, and Rhipicephalus sanguineus.1,2

Learn more about Simparica.

Contact Zoetis Customer Service at 1-888-ZOETIS-1 or 1-888-963-8471.

References: 1. Six RH, Geurden T, Carter L, et al. Evaluation of the speed of kill of sarolaner (Simparica™) against induced infestations of three species of ticks (Amblyomma maculatum, Ixodes scapularis, Ixodes ricinus) on dogs. Vet Parasitol. 2016;222:37-42. 2. Six RH, Everett WR, Young DR, et al. Efficacy of a novel oral formulation of sarolaner (Simparica™) against five common tick species infesting dogs in the United States. Vet Parasitol. 2016;222:28-32.

All trademarks are the property of Zoetis Services LLC or a related company or a licensor unless otherwise noted. © 2017 Zoetis Services LLC. All rights reserved. SMP-00307

Essentials

PRACTICAL PARASITOLOGY Heartworm Infection in Ferrets

14

NUTRITION NOTES Nutritional Management for Gastrointestinal Disease

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FROM THE FIELD Focus on Overweight and Obesity in Cats

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PRACTICAL PARASITOLOGY

Heartworm Infection in Ferrets Leonie Kondert, DVM Joerg Mayer, DVM, MS, DABVP, DACZM University of Georgia shutterstock.com/Burdun Iliya

Because of their friendly and playful character, ferrets are commonly kept as pets in the United States.

Ferrets (Mustela putorius furo) belong to the family Mustelidae. The genus Mustela includes weasels, the European mink, the American mink, ferrets, and South American weasels. Ferrets were originally domesticated and bred to hunt rabbits; although this practice is not common in the United States, it is still in use in Europe and Asia.1 Ferrets, like more than 30 other mammalian species with documented infections, are susceptible to infection with heartworms (FIGURE 1).2

ETIOLOGY OF HEARTWORM DISEASE The first description of a heartworm infection was written in Italy in 1626; the first description in the United States was in 1847.3 Heartworm disease (HWD) is a vector-borne disease caused by the filarial nematode Dirofilaria immitis.

This parasite belongs to the superfamily Filarioidea and the family Onchocercidae.

Transmission is primarily via 3 species of mosquitos (Aedes trivittatus, Aedes sierrensis, and Culex quinquefasciatus); however, 70 species of mosquitos can function as vectors for infection.

PREVALENCE

FIGURE 1. The right chamber of a ferret heart affected with Dirofilaria. Image courtesy of pathology service at the University of Georgia (UGA).

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HWD is widespread and can be found in North America, South America, Europe, Asia, and Australia.4,5 New models have been developed to predict HWD prevalence in dogs based on several factors (climate, geography, and society) and help in predicting outbreaks in the United States. The southeastern US has an exceptionally high risk of infection, but infections are described in all of the lower 48 states.6

ESSENTIALS

Infections with D immitis in ferrets are described in laboratory settings with a susceptibility of 100%.7 Multiple cases of HWD in client-owned ferrets have been reported; however, compared to cats and dogs, there is not as much data regarding prevalence and susceptibility for HWD in ferrets.8 Housing a ferret outside is not recommended in areas where heartworm prevalence in cats and dogs is high. Even housing a ferret indoors 100% of the time is not a guarantee that it will avoid infection. One study found that about 25% of indoor cats have HWD.9

CLINICAL SIGNS The clinical signs described in ferrets depend on the stage of HWD but are often associated with heart failure (FIGURE 2). Signs include dullness, anorexia, coughing, dyspnea, systolic heart murmur, pleural effusion, ascites, anemia, intravascular hemolysis, and acute renal and hepatic failure.1 Bilirubinuria is a frequently described sign. In a study of clinical observations of naturally occurring HWD in ferrets, bilirubinuria was observed in 83% of the cases.10 A rare case of an aberrant larval migration infesting the subdural space of the cranial cavity was reported in Europe in 2010.11 HWD may be misidentified in ferrets. A study in 2008 showed HWD was diagnosed in 11 black-footed ferrets using an antigen-based enzyme-linked immunosorbent assay (ELISA). Polymerase chain reaction (PCR) amplification of the 5S spacer region of rDNA of the filarial sequences showed only 76% conformity with D immitis; it was reported that the population was infected with an undescribed filarial species.12

FIGURE 2. A necropsy of a ferret affected with Dirofilaria.

Note the globoid shape of the heart. Image courtesy of pathology service at UGA.

Pathogenesis The life cycle of D immitis is 210 to 270 days.

Female mosquitos can be infected with microfilariae during feeding on an infected host. After ingestion, the microfilariae transform into first-stage larvae (L1). Depending on temperature, L1 molt into infective third-stage larvae (L3) within about 10 to 14 days. The infective L3 are deposited on the skin of a potential host by the feeding mosquito. They enter the subcutaneous tissue of the host through the bite wound and, after a few days, transform into fourth-stage larvae (L4).

The L4 migrate through the subcutaneous and muscle tissue toward the thorax, where they molt to juvenile worms 50 to 70 days postinfection. The immature worms enter the bloodstream via peripheral veins and finally infest the pulmonary vasculature.

A mean duration of 70 days after inoculation has been described for this migration. The juvenile worms reach maturity in the pulmonary arteries 180 days after infection. Mating takes place in the pulmonary arteries, and microfilariae are found in circulation at approximately 180 to 210 days after initial infection.3 Ferrets can be severely affected by a low heartworm burden of 1 to 2 adult worms.13

DIAGNOSTICS Results of tests using antigen detection of a glycoprotein secreted by female heartworms will be falsely negative in the case of a male-only infection. Screening by blood test is not reliable in ferrets; symptomatic animals should be radiographed to evaluate the cardiac silhouette as the first step (FIGURE 3). A biochemistry profile and a complete

FIGURE 3. Lateral thoracic radiograph of the thorax of a ferret. A globoid cardiac silhouette is a common finding in thoracic radiographs of affected animals. Image courtesy of radiology service at UGA.

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blood cell count should always be performed. Changes commonly seen include elevated liver enzymes, azotemia, bilirubinemia, eosinophilia, basophilia, neutrophilia, nonregenerative anemia, and thrombocytopenia.3 If D immitis microfilariae are observed on a blood smear (FIGURE 4), the diagnosis of HWD is definitive. However, the Difil (Vetoquinol.com) or modified Knott’s test can have false-negative results owing to the normally low levels and transient nature of the microfilaremia in ferrets.13

Housing a ferret outside is not recommended in areas where heartworm prevalence in cats and dogs is high. Even housing a ferret indoors 100% of the time is not a guarantee that it will avoid infection. In addition to medical prevention of HWD, housing the ferret in a mosquitofree environment is highly desirable.

Molecular genetic structures can be detected on PCR.3 D immitis can be observed via echocardiography as abnormal hyperechoic structures in the right atrium and/or right ventricle.14 Nonselective angiography provides a sensitive method of detection of adult heartworms in the cranial vena cava.15

TREATMENT The decision of which treatment is most suitable for the patient should be based on whether the

FIGURE 4. D immitis microfilaria in a canine blood smear.

Image courtesy of Dr. Megan Caudill, UGA.

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PRACTICAL PARASITOLOGY

patient is in heart failure. Stabilization of a ferret in heart failure is similar to that for a cat or dog, administering the following as necessary: ■■ Oxygen

supplementation

■■ Tranquilization

of the patient with midazolam 0.1 to 0.3 mg/kg IM8

■■ Furosemide ■■ Benazepril

1 to 4 mg/kg PO, IM, or IV q6–24h13

0.25 to 0.5 mg/kg PO q24h8

■■ Pimobendan

0.5 to 1.25 mg/kg PO q12h8

Once the patient is stable, the decision to pursue a surgical approach or medical management must be made (TABLE 1). All the published treatment options in ferrets consist of extralabel protocols.

Alleviation of clinical signs with prednisone 0.5 mg/kg PO q12h can be elected if the patient is not stable enough for more invasive treatment.14 Successful transvenous extraction of adult heartworms has been described in a 10-monthold ferret.16 After the surgery, the patient was medically managed with corticosteroids and a monthly heartworm preventive.16 If a more conservative approach is warranted, different protocols have been studied. Protocols using melarsomine 2.5 to 3.25 mg/kg IM have been described using a 2- or 3-injection protocol similar to that used in treating dogs. To prevent pain associated with the injections, sedation or anesthesia of the patient is necessary. Strict cage rest is indicated after treatment, as there is a high risk of thromboembolism.

The use of a combination of ivermectin 0.05 to 0.2 mg/kg IM every 30 days and prednisone 0.5 mg/kg PO q12h is indicated if the patient has a mild form of infection.13 Long-term treatment with moxidectin is described to be associated with fewer risks and can result in antigen-negative patients. In a study performed on 10 naturally infected ferrets, moxidectin was used at a dose of 0.17 mg/ferret SC, and 4 ferrets were reported to be antigen-negative after treatment.17 Because of the small sample size, we hesitate to recommend this protocol as a successful treatment option before further investigation has been performed. However, the longer course of treatment may result in greater endothelial damage from the prolonged presence of the parasites.18

ESSENTIALS

TABLE 1 Heartworm Treatment Options for Ferrets THERAPY

MEDICATION PROTOCOL

HEALTH RISK

Conservative: Slow kill adulticide

Prednisone 0.5 mg/kg PO q12h Ivermectin 0.05–0.2 mg/kg IM every 30 days

Low

Conservative: Slow kill adulticide

Moxidectin 0.17 mg/ferret SC every 30 days

Low

Adulticide

Melarsomine dihydrochloride 2.5–3.25 mg/kg IM on day 0, day 1, and day 31

High

Surgery

Transvenous extraction of adult heartworms

High

PREVENTIVE MEDICINE There are several options for medical prevention of HWD in ferrets (TABLE 2). The use of ivermectin 0.05 to 0.2 mg/kg PO every 30 days, milbemycin oxime 1.15 to 2.33 mg/kg PO every 30 days, or selamectin 6 to 18 mg/kg topically every 30 days is described.8,10,20 In one study, a combination of 10% imidacloprid and 1% moxidectin 0.4 mL/ferret (up to 4 kg) topically every 30 days was a successful preventative.21

of this life-threatening disease, and we hope more data will become available from cases managed in different clinics across the country.

As with other pets, prevention of HWD is recommended.

Although the vast majority of ferrets are housed indoors, a preventive approach should be implemented year-round, especially in endemic areas.

To see the references for this article, please visit tvpjournal.com.

In addition to medical prevention of HWD, housing the ferret in a mosquito-free environment is highly desirable.1 D immitis resistant to macrocyclic lactones have been described in the US Mississippi Delta.5 Therefore, patients receiving macrocyclic lactones to treat HWD should be screened annually for circulating microfilariae.3 However, since circulating microfilariae are not always present in an infected ferret, this screening method must be used with caution.

SUMMARY The diagnosis and management of HWD in ferrets is not as straightforward as in dogs and cats for a variety of reasons. Unfortunately, there are fewer data available for ferrets regarding management TABLE 2 Heartworm Preventives For Ferrets MEDICATION

DOSAGE

Ivermectin

0.05–0.2 mg/kg PO every 30 days

Milbemycin oxime

1.15–2.33 mg/kg PO every 30 days

Selamectin*

6–18 mg/kg topical every 30 days

10% Imidacloprid + 1% moxidectin

0.4 mL/ferret (up to 4kg) topically every 30 days

Leonie Kondert Leonie Kondert, DVM, served as a Zoo and Exotic Medicine intern at the University of Georgia. Dr. Kondert received her DVM from the University of Veterinary Medicine in Vienna, Austria and successfully completed the ECVFG exam. She also completed one year of training in Zoological Pathology at the Research Institute of Wildlife Ecology and worked three years with small animals in private practice. Her research interests include small mammal medicine and surgery.

Joerg Mayer Joerg Mayer, DVM, MS, DABVP, DACZM, received his doctoral degree in veterinary medicine from the University of Budapest, Hungary. He moved to the United States for an internship in zoological medicine and surgery at the Roger Williams Park Zoo in Providence, Rhode Island. Dr. Mayer then attended the Royal Veterinary College in London, England, to study for his master’s degree in wild animal health. After 10 years at Tufts University as the head of the clinical service for exotic animals, he became an associate professor in zoological medicine at the University of Georgia. He lectures regularly at national and international conferences on all aspects of exotic animal medicine, and he has published many scientific articles and book chapters, some of which have been translated into French, Spanish, and Portuguese.

*Selamectin is considered a very safe preventive; even at a high dose of 35 mg/kg, no side effects have been reported in ferrets.19

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NUTRITION NOTES

Diarrhea, Vomiting, and Food, Oh My!

Nutritional Management for Gastrointestinal Disease Angela Witzel, DVM, PhD, DACVN The University of Tennessee College of Veterinary Medicine shutterstock.com/Javier Brosch

Nutritional management of gastrointestinal disease is a broad topic incorporating both acute and chronic diseases of the stomach, small intestines, pancreas, gallbladder, and colon. As such, this article introduces the types of gastrointestinal diets available to help the clinician decide which one is best based on their nutritional components.

TYPES OF GASTROINTESTINAL DIETS There are 4 broad categories of diets for managing gastrointestinal disease: low-residue, fiber-enhanced, low-fat, and hypoallergenic. Homemade diets can also be used for managing disease, but vary tremendously based on their formulation.

Low-residue Diets Low-residue diets can be defined as having protein digestibility >87% and fat and carbohydrate digestibility >90%. These diets typically have refined ingredients and are low in fiber (<3-5% on a drymatter basis). The benefits of low-residue diets are they can speed movement of food through the stomach and ease absorption in compromised intestine.

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Fiber-enhanced Diets Fiber-enhanced diets may be designed for gastrointestinal disease or diabetes mellitus.

Fiber can be categorized based on its solubility in water or its ability to be fermented by intestinal bacteria. Soluble fiber sources dissolve in water to form a thick, viscous gel, which will slow the movement of ingesta through the intestines.

Soluble fiber sources also tend to be fermentable and can produce gases and physiologically active byproducts within the intestine. Insoluble fibers do not dissolve in water and tend to have low fermentability. Thus, they can be viewed as metabolically inert and provide bulking of stool and water absorption as they move through the intestine. Insoluble fibers tend to stimulate colonic stretch receptors, which can cause diarrhea. Ideally, fiber-enhanced diets would contain a combination of both soluble and insoluble fibers to provide a balanced effect. Too much of either type of fiber could result in soft stools, constipation, or excessive gas. Also, note that crude fiber listing on the guaranteed analysis of pet food labels do not capture the soluble fiber fraction of the diet and may underestimate total dietary fiber (TDF).

ESSENTIALS

Low-fat Diets

Small Intestinal Disease

Low-fat diets typically have fat contents between 18-25 g/1000 kcal. Lower fat diets can be useful for reducing pancreatic stimulation and speeding movement through the stomach in vomiting animals. Low-fat diets are not appropriate for weight loss because they are not fortified with nutrients to offset low-calorie intake. Weight loss diets are also typically lower in fat than standard diets, but the fiber content and calorie density may not be appropriate for animals with poor appetites or vomiting. In addition, weight-loss diets usually are not restricted as low in fat as the gastrointestinal low-fat diets.

Acute small intestinal (SI) diarrhea with or without vomiting will often benefit from a low-residue diet. As normal digestion and absorption may be compromised. Small, frequent meals are recommending and early feeding for the intestines are best.

Hypoallergenic Diets Diets designed to reduce symptoms of food allergies can be placed into 2 broad categories: novel protein or hydrolyzed. Novel protein diets use uncommon protein and carbohydrate ingredients to lessen the chance of exposure and a subsequent allergic response. In humans, most food allergens are glycoproteins that range in size from 14,000 to 40,000 Da. Proteins within range are large enough to activate B and T cells, but small enough to pass through mucosal membranes and interact with the immune system. Hydrolyzed proteins are low molecular weight peptides (<18,000 Da) with reduced antigenic potential because they are too small to bind with immunoglobulins.1 As a result, they are less likely to elicit a response from the dog’s immune system. Free amino acids are not allergenic but cannot be used due to their bitter taste and high osmolarity. There are many of hypoallergenic diets on the market. Novel protein diets are available over-the-counter (OTC) or by veterinary prescription. OTC tend to have a higher likelihood of contamination with common pet food proteins as compared to veterinary therapeutic diets.2

SPECIFIC TYPES OF GASTROINTESTINAL DISEASE Vomiting Vomiting is the most common clinical sign of gastric disease. Dietary goals for vomiting are to minimize gastric irritation, promote gastric emptying, normalize motility and prevent gastroesophageal reflux. Fat and fiber delay gastric emptying, so choosing a lower fat, low-residue diet is usually ideal to manage vomiting and reflux. For acute, frequent vomiting food may be withheld for 24 hours. Small, frequent meals (3-6 per day) can also speed passage of food through the stomach.

Inflammatory bowel disease (IBD) is described as a group of chronic, idiopathic inflammatory disorders of the gastrointestinal tract. Severity can vary from mild- to life-threatening protein losing enteropathy (PLE). Clinical signs depend on section of bowel affected. Key nutrition factors for IBD include: ■■ Avoid

excessive dietary protein to minimize antigens that elicit an immune response (PLE is an exception and requires high protein)

■■ Feed

a low-residue diet as absorption may be impaired

■■ Utilize ■■ Feed

a novel protein and/or hydrolyzed protein diets

small, frequent meals

Protein losing enteropathies such as lymphangiectasia require a low-fat diet. Long chain triglycerides, the most common form of dietary fat, stimulate lymph flow and increase protein leakage through the lymphatic vessels. Lymphangiectasia can be primary, but is often secondary to IBD. A low-fat, high-protein, low-residue diet is desired for these cases. Our nutrition practice usually assumes cases of lymphangiectasia are secondary to IBD unless proven otherwise, and also utilize hydrolyzed or novel protein diets for management. A low-fat, low-residue diet that is hypoallergenic and high protein is difficult to obtain. Our practice often utilizes Purina Feline HA for our canine patients as it meets most of these criteria. A portion of the fat from this diet comes from medium chain triglycerides (MCT) that passively diffuse from the GI tract to the portal system and partially bypass the lymphatic system. Thus, calorie density is maintained while lowering long chain fatty acids.

Short Bowel Syndrome develops from massive resection of the small intestine and may result in malabsorption due to lack of surface area. Cobalamin deficiency may occur if ileum is resected. These cases benefit from low-residue diets. Moderateto high-fat, energy-dense foods that are low to moderate in fiber are ideal. Supplementation of fat soluble vitamins and cobalamin may be needed and patients should be fed small, frequent meals.

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Dysbiosis of bacterial flora in the intestines can lead to diarrhea and may be present in 50% of dogs with diarrhea.

Dysbiosis is often associated with exocrine pancreatic insufficiency (EPI). Laboratory evaluation involves a normal to high trypsin-like immunoassay (TLI) with a low B12 and high folate. These patients may do best on either a low-residue or fiber-enhanced diet. Additional probiotics, prebiotics, and antimicrobial therapies may also be needed.

Pancreatic Disease Pancreatitis is the most common disease of the pancreas and can be acute or chronic in nature. Patients with acute pancreatitis patient will benefit from early enteral nutrition. Unless vomiting is uncontrollable with antiemetics, small amounts of nutritional support should be given as soon as possible. Typically a nasoesophageal feeding tube is used and a liquid product enteral product is used. For chronic pancreatitis in dogs the main nutrient of concern is fat. A low-fat diet is best and the degree of fat restriction will be dependent on case severity.

Protein can also stimulate the pancreas, so high protein diets should be avoided. Cats with acute pancreatitis can be treated similar to dogs with a low-fat, moderate protein diet. Cats with chronic pancreatitis typically do not require diet changes as diet does not appear to be a factor in their disease progression or outcome.

The exocrine pancreas secretes numerous enzymes to digest fats, proteins, and carbohydrates. Animals must lose approximately 90% of their functional capacity before exocrine pancreatic insufficiency (EPI) produces clinical signs. EPI characterized by chronic small bowel diarrhea with steatorrhea and voluminous diarrhea. Patients also have ravenous appetite with weight loss. The best treatment for EPI is supplementation with pancreatic enzymes. Diet modification doesn’t appear to make much difference in these cases. However, absorption of fat-soluble vitamins

Angela Witzel Dr. Angela Witzel performed her DVM, PhD, and residency training at the University of Tennessee College of Veterinary Medicine. Dr. Witzel is a Diplomate and former President and Chair of the Board for the American College of Veterinary Nutrition. She is also a Clinical Associate Professor of Nutrition at the University of Tennessee Veterinary Medical Center. Her areas of research interest include adipose hormones, body composition, and obesity management.

(A, D, E, and K) may be impaired and cobalamin may need to be supplemented until clinical signs are well controlled.

Large Intestinal Disorders Colitis is a common disorder with many causes. In general, high-fiber diets are helpful with colitis to support the growth of beneficial bacteria and to help with water balance. If a high-fiber diet does not improve large bowel diarrhea, a low-residue diet may be used to minimize nutrients reaching the colon. Finally, if the diarrhea is not responsive to fiber or high digestible diets a low-allergen diet may be used in case there is an immune-mediated component to the disease.

Flatulence is an annoyance to pet owners and the dietary goal is to reduce intestinal gas production. Low-residue diets with a fat content lower than their current diet may be helpful. Highly fermentable carbohydrate sources should be avoided (beans, cruciferous vegetables). Alphagalactosidase (Beano) may also decrease flatulence by improving digestion of carbohydrates. Outdoor exercise may also help expel gases in a less offensive environment.

Prebiotics and Probiotics Prebiotics are starches and fibers resistant to digestion. Examples include: Fructooligosaccharides (FOS), Mannanoligosaccharides (MOS), Galactooligosaccharides (GOS), Fermentable fibers.

Indications for prebiotics include antibiotic-associated diarrhea, traveler’s diarrhea, gastroenteritis, normalizing bowel function, colitis, and irritable bowel problems.

According to the food and agricultural organization (FAO) and the world health organization (WHO), probiotics are defined as “Live microorganisms which when administered in adequate amounts confer a health benefit on the host.” Ideally probiotics should originate in the species being treated, be nonpathogenic, be resistant to digestion by gastric acid and intestinal enzymes, able to adhere to the intestinal epithelium, and be capable of influencing host immune responses.

Probiotics can promote normalized microflora and may have role in allergies. They can also help to inhibit binding of pathogenic bacteria. Many products may not contain the numbers of viable bacteria they claim.

References 1. Yunginger JW. Food antigens. In: Metcalfe DD, Sampson HA, Simon RA, eds. Food allergy: adverse reactions to foods and food additives.

Boston (MA): Blackwell Scientific; 1991:36–51.

2. Raditic DM, Remillard RL, Tater KC: ELISA testing for common food antigens in four dry dog foods used in dietary elimination trials. J Anim Physiol Anim Nutr 2011, 95.

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F

rom the Field shares insights from Banfield Pet Hospital veterinary team members.

Drawing from the nationwide practice’s extensive research, as well as findings from its electronic veterinary medical records database and more than 8 million annual pet visits, this column is intended to explore topics and spark conversations relevant to veterinary practices that ultimately help create a better world for pets.

ESSENTIALS

FROM THE FIELD

Focus on Overweight and Obesity in Cats Kirk Breuninger, VMD, MPH, DACVPM Banfield Pet Hospital Vancouver, Washington shutterstock.com/Helle

In the last From the Field column, Banfield Pet Hospital reported on dog-specific findings from our recently released 2017 State of Pet Health Report, which highlights a widespread trend of overweight pets nationwide. When we looked at medical records from the more than 500,000 cats cared for at Banfield hospitals in 2016, we found that felines are faring even worse than their canine counterparts with an increase of over 169% over the past 10 years in overweight cats.

The prevalence estimates for each state are listed on stateofpethealth.com. How did your state do?

Here are some tips and tricks for talking with your clients about their cat’s weight: is key. Have cat-friendly strategies in place in your hospital. This will help create a less stressful atmosphere for your feline patients and will encourage pet owners to bring their cats in for regular check-ups and nutritional counseling, which can help keep their cats at a healthy weight.

There are some great resources on cat friendly practices through the American Association of Feline Practitioners (AAFP). Strategies include:

■■ Prevention

The top five states with the highest prevalence of overweight cats included Minnesota (46%), Nebraska (43%), Iowa (42%), Idaho (40%) and Delaware (39%).



Designate separate areas for cats in the waiting and treatment areas



Provide a cat-only exam room



hen possible, complete W procedures in the exam room



Consider providing a hiding place for the cat by utilizing kennel covers (when medically appropriate)



Use calming pheromone sprays or diffusers



Brush up on feline and lowstress handling techniques

States with the Most Obese Cats The top five states with the highest prevalence of overweight cats included Minnesota . . . . . . . . 46% Nebraska . . . . . . . . . 43% Iowa . . . . . . . . . . . . . . . 42% Idaho . . . . . . . . . . . . . . 40% Delaware . . . . . . . . . 39% Find out how your state ranks at stateofpethealth.com.

22

FROM THE FIELD

ESSENTIALS

don’t tell. Oftentimes, it is difficult for cat owners to recognize that their pet is overweight.

This may be due to the distribution of fat on a cat’s body, the amount of fur present, or misconceptions about ideal weight. A graphic of body condition scoring (FIGURE 1) can be a useful tool as you have these conversations.

■■ Show,

Kirk J. Breuninger Kirk J. Breuninger, VMD, MPH, is a member of the Banfield Applied Research and Knowledge (BARK) team, where he performs and disseminates research that contributes to advancing medical quality, patient safety, and medical decision making. He received his veterinary degree from University of Pennsylvania and his Master of Public Health degree from Temple University. He is an inaugural member of the AVMA Early Career Development Committee, was awarded the 2009 George B. Wolff Legislative Leadership Award, and was recognized as the 2015 Pennsylvania Veterinarian of the Year by the Pennsylvania Veterinary Medical Association.

treats in moderation. Advise clients to take note of how many treats they give their cat per day. Treats should not make up more than 10% of a cat’s daily caloric consumption.

■■ Give

exercise. Getting cats to exercise can be a challenge. Determining the right strategy is important—even increasing exercise by 10 minutes every day can have a positive impact on a cat’s overall well-being. Some options include:

■■ Encourage



Using a laser pointer



Playing with a feather toy; or



Increasing mealtime activity by dividing meals into multiple dishes and placing throughout the house.

View the State of Pet Health For more client education tools, as well as a host of other resources, visit stateofpethealth.com.

HOW CAN I TELL IF MY PET IS OVERWEIGHT? Body condition scoring is a way to determine if a pet is underweight, ideal weight or overweight. Discuss your pet's current and ideal weight with your veterinarian.

DOGS

CATS

top view | side view

BODY CONDITION SCORE

top view | side view

Request Your Vet Guide Today!

1 VERY THIN

Give us a call 800.742.0516

Severely defined ribs and waist

2 THIN

Easily visible ribs and waist

3 IDEAL WEIGHT Ribs easily felt, but not seen Obvious waist

4 OVERWEIGHT

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Ribs not easily seen or felt Waist barely visible

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FIGURE 1. 2016 overweight prevalence in cats.

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Fewer doses help improve adherence

More convenient for pet owners Four doses of BRAVECTO® provide nearly a full year of flea and tick protection instead of having to treat 12 times with a monthly product.

Fewer potential gaps in protection1-4 Fewer doses per year also means less chance of pet owners forgetting and missing one.

Available by prescription only Administer the first dose in your clinic and rest assured your patient is protected for up to 12 weeks.*

Easy to administer BRAVECTO® Chew is well tolerated and palatable Dogs love the tasty pork flavor making treatment less stressful

Available in a topical application for dogs and cats Innovative formula is applied topically but, like the chew, it works systemically2,3

93.2% of dogs ate BRAVECTO® Chew voluntarily1,5

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Safety you can trust FDA approved and veterinarian recommended BRAVECTO® Chew and Topical Solution for Dogs are approved for pregnant, breeding and lactating dogs.1,2,5,6 BRAVECTO® is also approved for use in dogs 6 months of age or older who weigh at least 4.4 pounds.1,2 BRAVECTO® Topical Solution for Cats is approved for cats and kittens 6 months of age and older and weighing 2.6 pounds or greater.3

Veterinarians recommend year-round flea and tick protection What do dog owners think?

62%

of dog owners remembered their veterinarian’s exact recommendation7

73%

of dog owners agree that their pets should have 12 months of flea and tick protection7

Is everyone following the 12-month recommendation? No. The average dog owner applies approximately 4.6 monthly flea treatments in a year.8

BRAVECTO® can help close the compliance gap Pet owners prefer BRAVECTO®

9 to 1 over monthly treatments

Ask your Merck Animal Health Rep about BRAVECTO® or visit Bravectovets.com

9

®

BRAVECTO® Chew for Dogs [prescribing information]. Madison, NJ: Merck Animal Health; 2014.

BRAVECTO® Topical Solution for Dogs [prescribing information]. Madison, NJ: Merck Animal Health; 2016.

3 BRAVECTO® Topical Solution for Cats [prescribing information]. Madison, NJ: Merck Animal Health; 2016.

4 Rohdich N et al. Parasites & Vectors. 2014;7:83.

5 Freedom of Information Summary, NADA 141-426. Approved May 15, 2014.

6 Freedom of Information Summary, NADA 141-459. Approved 2016.

7 Lavan et al. P&V. 2017; 10:284.

8 Brakke Consulting US Flea Control & Heartworm Markets report; 2015.

9 Lavan et al. J Vet Sci Technol. 2017; 8:439.

1 2

*BRAVECTO® kills fleas and prevents flea infestations for 12 weeks. BRAVECTO® Chew and BRAVECTO® Topical Solution for Dogs kills ticks (black-legged tick, American dog tick, and brown dog tick) for 12 weeks and also kills lone star ticks for 8 weeks. BRAVECTO® Topical Solution for Cats kills ticks (black-legged tick) for 12 weeks and American dog ticks for 8 weeks.

IMPORTANT SAFETY INFORMATION: BRAVECTO® has not been shown to be effective for 12-weeks’ duration in puppies or kittens less than 6 months of age. BRAVECTO® Chew and BRAVECTO® Topical Solution for Dogs: The most common adverse reactions recorded in clinical trials were vomiting, decreased appetite, diarrhea, lethargy, polydipsia, and flatulence. BRAVECTO® is not effective against lone star ticks beyond 8 weeks of dosing. BRAVECTO® Topical Solution for Cats: The most common adverse reactions recorded in clinical trials were vomiting, itching, diarrhea, hair loss, decreased appetite, lethargy, and scabs/ulcerated lesions. BRAVECTO® is not effective against American dog ticks beyond 8 weeks of dosing. For topical use only. Avoid oral ingestion. The safety of BRAVECTO® has not been established in breeding, pregnant and lactating cats. Use with caution in cats with a history of neurologic abnormalities. Neurologic abnormalities have been reported in cats receiving BRAVECTO®, even in cats without a history of neurologic abnormalities.

Copyright © 2018 Intervet Inc., d/b/a Merck Animal Health, a subsidiary of Merck & Co. Inc. All rights reserved. US/BRV/1117/0105

See full Prescribing Information on page 2.

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Lulich JP, Kruger JM, MacLeay JM, et al. Efficacy of two commercially available, low-magnesium, urine-acidifying dry foods for the dissolution of struvite uroliths in cats. J Am Vet Med Assoc. 2013;243(8):1147-1153. Average 27 days in vivo study in urolith forming cats.

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Features

CONTINUING EDUCATION: GASTROENTEROLOGY Inflammatory Bowel Disease in Dogs and Cats

28

CONTINUING EDUCATION: DERMATOLOGY Canine Atopic Dermatitis: Updates on Diagnosis and Treatment

42

FLUID THERAPY Fluid Therapy for Hospitalized Patients: Part 1

60

PEER REVIEWED

CONTINUING EDUCATION

CONTINUING EDUCATION

GASTROENTEROLOGY

Inflammatory Bowel Disease in Dogs and Cats Kayode Garraway, DVM Karin Allenspach, DVM, PhD, DECVIM-CA Albert Jergens, DVM, MS, PhD, DACVIM (SAIM) Iowa State University College of Veterinary Medicine

Inflammatory bowel disease (IBD) is a multifactorial disease of dogs and cats characterized by chronic enteropathies that can significantly impact quality of life. These enteropathies are usually thought of as being food responsive, antibiotic responsive, steroid responsive, or refractory, regardless of immunosuppressive therapies (idiopathic IBD).

Histologically, the small intestine, large intestine, or both can be affected. Lymphocytes and plasmacytes are the most common cell infiltrates within the lamina propria of the gastrointestinal (GI) tract; eosinophils, macrophages, and neutrophils can also be appreciated, but less frequently.

Although the exact etiologies of IBD are unknown, multiple factors can contribute to this persistent disease state. A confounding issue is that many healthy dogs and cats are exposed to similar factors relative to animals affected by

IBD, but never become affected. This article summarizes and discusses the believed influences on gut inflammation, potential diagnostics, treatment options, and clinical outcomes in light of the most recent literature available.

FACTORS ASSOCIATED WITH GASTROINTESTINAL INFLAMMATION Factors currently believed to be associated with GI inflammation include: ■■ Genetics ■■ The

mucosal immune system and immune responses

■■ Environmental ■■ Microbial

factors

factors1,2

These have been evidenced by human, mouse, canine, and feline models.1–13

CREATURE DISCOMFORTS Inflammatory bowel diseases are the most common cause of chronic vomiting and diarrhea in dogs and cats. The term IBD is used to describe a group of conditions characterized by inflammation of the gastrointestinal tract and persistent or recurrent GI signs..

shutterstock.com/Chendongshan

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Genetics The genetic component believed to be associated with an increased risk of IBD is well documented in humans and involves mutations in pattern recognition receptors such as nucleotide binding oligomerized domain 2, Toll-like receptors (TLRs), and interleukin-23.1,3,5,8â&#x20AC;&#x201C;10,12,14 These receptors sense pathogen-associated molecular patterns in the region of the immediate cell surface or intracellular environment.

Specific breeds of dogs are recognized as being prone to chronic enteropathies, which likely suggests a genetic component (TABLE 1).

Although a genetic component is not as well recognized in cats, Siamese and other oriental breeds have been suggested to be more predisposed to developing IBD.22,23 In our experience, this has not necessarily been the case, as domestic shorthaired and longhaired breeds account for most cats presenting and diagnosed at our facility.

The pathophysiology behind breed predispositions is not well understood, but triggers have been identified in some breeds. In boxers with granulomatous colitis, genome analysis has identified disease-associated singlenucleotide polymorphisms (SNPs) that may affect killing of pathologic Escherichia coli. The presence of these adherent and invasive E coli within mucosal macrophages of specifically boxers, and this organismâ&#x20AC;&#x2122;s eradication with tailored antibiotic implementation further suggests a breed-specific association relative to disease pathogenesis as well as clinical response.8,15-18,24,25

Genetic analysis of German shepherds has shown that several SNPs in the TLR 4 and TLR 5 genes are significantly associated with the incidence of lymphocyticâ&#x20AC;&#x201C;plasmacytic IBD.26 These TLRs are a class of proteins of the innate immune system that span the membrane of sentinel cells, such as macrophages and dendritic cells, and are important in the recognition of lipopolysaccharide of gram-negative bacteria, lipoteichoic acid of gram-positive bacteria, and bacterial flagellin.

TLR 2 mRNA expression, which has been correlated with the clinical severity of IBD, has been noted to be higher in the duodenum of affected dogs compared with healthy dogs.1 In mouse models, TLR 2 has been implicated in the homeostasis of intestinal tissue after injury.1,27,28

Mucosal Immune System and Immune Responses The mucosal immune system, immune tolerance, and other innate and adaptive immune processes also play roles in the development of chronic inflammation of the GI tract.

Immunoglobulin A (IgA), important in the mucosal defense system, provides a barrier to keep luminal bacteria from crossing the luminal epithelial cells. Loosely and tightly adherent mucus produced by goblet cells and tight junctions between luminal epithelial cells also provide an immediate barrier. Any irregularity in these barriers can lead to the transposition of GI pathogens and commensals and result in chronic inflammation.

TABLE 1 Chronic Enteropathies Associated With Specific Dog Breeds DOG BREED

ASSOCIATED ENTEROPATHY

Soft-coated wheaten terrier

Protein-losing enteropathy

Basenji

Immunoproliferative enteropathy

Boxer French bulldog

Granulomatous colitis, also known as histiocytic ulcerative colitis4,8,15-18

German shepherd

Lymphocytic-plasmacytic inflammation4,8,19,20

Norwegian lundehund

Inflammatory bowel disease21

Yorkshire terrier

Protein-losing enteropathy with lymphangiectasiaa

a Protein-losing enteropathy with lymphangiectasia in Yorkshire terriers can have an inflammatory component causing lymphatic dilation; often, IBD is a secondary diagnosis to lymphangiectasia in these dogs.

30

CE: INFLAMMATORY BOWEL DISEASE

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The focus of inflammation can exacerbate the degradation of tight junctions. T helper 1 cells and complementary T cell subsets are involved in the secretion of proinflammatory cytokines, whereas T regulatory cells antagonize proinflammatory states for appropriate homeostasis of the gut adaptive immune system. In IBD, this balance is lost.29

Alteration of the microbiota by manipulation of commensals, and restricting the diet to one containing fewer structural carbohydrates and more fat, results in decreased production of shortchained fatty acids needed for overall gut health, providing further evidence for the interplay between the factors predisposing to IBD.2,8,23

Intensive and hyperresponsive states of inflammation result from aggressive T-cell responses to antigens and pathogens with upregulation of inflammatory mediators, as well as defects in microbial extermination and downregulation of inflammatory control mediators.13,23

CLINICAL SIGNS

Environmental Factors Environmental factors encompass a number of possible etiologies. In humans with chronic enteropathies, etiologies include stress, diet, and previous exposure to pharmaceuticals, including antibiotics.9,29,30 Although stress has not been well established in the literature as an etiology in dogs and cats, stressful events for cats have been associated with other inflammatory diseases, such as feline idiopathic cystitis and recrudescence of feline upper respiratory tract infections.31 There is a diet-responsive component to IBD, as noted in humans.8,12,23,29 Some cats and dogs respond favorably to novel protein and/or hydrolyzed protein diets. Because multiple dietary components are recognized by the GI immune system as foreign antigens,32 the thought is that decreasing the load of antigens decreases inappropriate immune responses.

Clinical signs of IBD can include vomiting, diarrhea, melena, hematochezia, weight loss, and hyporexia to anorexia, in any combination.

Some patients also present with clinical signs of disease progression, such as subcutaneous edema, pleural effusion, and ascites associated with hypoalbuminemia due to a related PLE.33 The presence of ongoing clinical signs lasting more than 3 weeks is the basis of classification of a chronic enteropathy.34 It is important to get a full history, which includes: ■■ Characterization

of clinical signs

■■ Duration ■■ Diet ■■ Therapies ■■ Response

to therapy

This comprehensive medical history ensures proper consideration of differentials with similar presentation and an appropriate diagnostic plan.

Microbial Factors Dysbiosis, or alteration of the normal microbial ecosystem within the intestine, is also observed in IBD.1 This has been demonstrated via fluorescence in situ hybridization analysis (FIGURE 1). Reported common changes in the normal commensals include decreases in Firmicutes (eg, clostridia, bacilli), decreases in Bacteroidetes, reduced Clostridium diversity, and increases in Enterobacteriaceae (such as E coli and Pseudomonas strains).2 Although dysbiosis would explain the occasional response to antibiotics, a number of these organisms are also found in healthy dogs and cats. Therefore, the combined action of the microbiome ecosystem and environmental factors, not solely the presence of these microflora, likely determines progression to IBD.

32

CE: INFLAMMATORY BOWEL DISEASE

FIGURE 1. Three-color fluorescence in situ hybridization identifies Cy-3-labeled Clostridia species (labeled orange) localized within adherent mucus of a colonic biopsy specimen obtained from a dog with IBD. The mucus is also occupied by other bacteria (total bacteria labeled green with FITC-Eub). The dark blue structures are nuclei (note some epithelial cells sloughed into the mucus) stained with DAPI. Courtesy of Angela Bryan.

CONTINUING EDUCATION

DIFFERENTIAL DIAGNOSIS A clinical diagnosis of IBD is based on7,33: 1. Presence of persistent (>3 weeks) GI signs 2. Inability to identify enteropathogens or other causes of GI disease 3. Histopathologic evidence of intestinal inflammation A diagnosis of IBD is primarily one of exclusion and requires elimination of IBD mimics through complete clinical examination, laboratory testing, and specialized instrumentation. Differentiation of severe IBD from well-differentiated (small cell) lymphoma may be especially problematic in cats.35,36

BOX 1. Diagnostic Differentials for IBD in Dogs and Cats GASTROINTESTINAL Parasites G iardia species 

T oxocara species



Trichuis species



Isospora species



Tritrichomonas species (cats)



P hysaloptera species



Ollulanus tricuspis (cats)



H eterobilharzia americana

Pathogenic bacteria E scherchia coli



After the exclusion of infectious and parasitic agents, nongastrointestinal disorders, exocrine pancreatic insufficiency, and intestinal structural abnormalities requiring surgery (BOX 1), the most common diagnoses of chronic enteropathy include food-responsive enteropathy (FRE), antibioticresponsive diarrhea (ARD), and idiopathic IBD.



Campylobacter species



Salmonella species



Mycobacteria species

Fungi and algae  H istoplasma species 

P rototheca species



P ythium insidiosum

Neoplasia Lymphoma

DIAGNOSTICS

 

Mast cell tumor

Fecal Examination



Adenocarcinoma



Leiomyosarcoma

Fecal examination by direct wet mount or flotation techniques can rule out parasitic causes for mucosal inflammation (BOX 1).



Gastrinoma

Giardia and Cryptosporidium infections are best detected using indirect fluorescent antibody tests.

Cats with chronic large bowel diarrhea should be screened for Tritrichomonas foetus infection by polymerase chain reaction.37

Hematology Routine hematology may reveal nonregenerative anemia reflective of chronic inflammation or enteric blood loss. Neutrophilia with or without a left shift is associated with erosive/ulcerative intestinal lesions. Eosinophilia is seen with some forms of IBD such as eosinophilic enteritis.1,4,38,39

Anatomic and functional disorders  Hypertrophic pyloric gastropathy 

Gastric emptying disorders

Other  Food allergy 

Dietary indiscretion



Transient gastroenteritis



Persistent foreign body

EXTRA-GASTROINTESTINAL Viruses  Feline leukemia virus 

Feline immunodeficiency virus

Organ dysfunction  H epatic disease 

Renal disease



Pancreatitis



E xocrine pancreatic insufficiency



Hyperthyroidism

Serum Biochemistry and Specialized Serologies



Hypoadrenocorticism

Results from biochemical analysis rarely provide definitive evidence for IBD, but they do facilitate the recognition of abnormalities in other organs that may cause GI signs.



Other  N eoplasia Persistent toxin exposure

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In cats with IBD, hyperproteinemia and mild elevation in liver enzymes (alanine aminotransferase and alkaline phosphatase) are often reported.7,22,40 Dogs with PLE frequently have hypoalbuminemia and hypoglobulinemia, which may be accompanied by hypocholesterolemia and hypocalcemia.

The presence of hypoalbuminemia correlates with a negative outcome in dogs.33,38 Cats with IBD may have increased serum pancreatic lipase concentrations (suggestive of pancreatitis). This association does not appear to influence clinical outcome, based on a recent report.41 However, increased serum pancreatic lipase concentrations in dogs with IBD have been associated with a poorer clinical outcome.42

Dogs and cats with chronic small bowel disease may have decreased serum cobalamin concentrations secondary to cobalamin malabsorption. Failure to recognize and correct hypocobalaminemia can delay clinical recovery, even with specific therapy for IBD.43 Hypocobalaminemia has also been correlated with a poor prognosis in dogs with chronic enteropathies.33

Diagnostic Imaging Abdominal radiographs can be used to assess the following: ■■ Extra-alimentary

tract disorders causing gastroenteritis (eg, neoplasia)

■■ Caudal

displacement of the small intestine and potential abdominal effusion with loss of cranial radiographic abdominal detail associated with pancreatitis (FIGURE 2)

■■ Overt

renal or hepatic changes (FIGURE 3) associated with dysfunction, damage, or neoplasia

Abdominal ultrasonography is superior to abdominal radiography in defining diffuse GI mucosal disease, intestinal wall thickness (FIGURE 4), and mesenteric lymphadenopathy seen with IBD as well as other infiltrative (eg, lymphoma) disorders.44

A

FIGURE 2. Lateral abdominal radiograph of a dog with pancreatitis. Note the loss of abdominal detail in the cranioventral abdomen with caudal displacement of the small intestine. Courtesy of Dr. Eric Van Eerde.

B

FIGURE 3. Lateral abdominal radiograph of a dog with hepatocellular carcinoma. Note the increase in soft tissue opacity (mass effect) in the cranioventral abdomen.

Courtesy of Dr. Eric Van Eerde.

34

CE: INFLAMMATORY BOWEL DISEASE

FIGURE 4. Ultrasound images showing jejunal muscularis thickening in a cat with IBD. (A) Cross-sectional image showing thickened small intestinal wall (0.44 cm). (B) Longitudinal section demonstrating a similar thickened appearance (0.38 cm). Normal small intestinal wall thickness in cats is reported as 0.16 to 0.36 cm.24 Courtesy of Dr. Jacob Ewing.

CONTINUING EDUCATION

Ultrasonographic examination allows fine-needle aspiration of focal wall thickening and enlarged lymph nodes to provide samples for cytologic analysis.

Cats with ultrasonographic evidence of muscularis propria thickening are more likely to have lymphoma than IBD.45

Endoscopy and Mucosal Biopsy Endoscopic examination with mucosal biopsy is essential to confirm a diagnosis of IBD and determine the extent of disease. The most widely reported endoscopic abnormalities seen with canine and feline IBD include mucosal friability, increased granularity, and mucosal erosions (FIGURE 5).7,33,46 The association between endoscopic lesions and disease activity in small animal IBD has been investigated to a limited extent. In separate investigations, endoscopic abnormalities of the duodenum of dogs with IBD did not always correlate with clinical indices of inflammation.33,47 The presence of severe mucosal lesions of the duodenum, but not the colon, was associated with a negative outcome in one study.33

C

The need to perform ileoscopy may be guided by the presence or absence of hypocobalaminemia, because cobalamin is absorbed in the ileum.

Histopathology Definitive diagnosis requires histopathologic evaluation of biopsy specimens. The microscopic findings in IBD consist of minimal to pronounced inflammatory cell infiltration, often accompanied by varying degrees of mucosal architectural disruption.

Unfortunately, biopsy interpretation is notoriously subjective, suffering from extensive interobserver variability, the technical constraints of specimen size, and procurement/processing artifacts inherent in evaluation of endoscopic specimens.48

B

One recent effort to standardize the assessment of GI inflammation resulted in a histopathologic monograph that defines numerous morphologic and inflammatory features in endoscopic biopsies.39 However, even with this standardized scheme, there was very poor agreement between pathologists,49 resulting in the design of a simplified model for IBD, currently under review.50

D

Recent studies indicate that changes in mucosal architecture, such as villous morphology and goblet cell mucus content, are related to the presence and severity of GI disease. These studies have used quantitative, observer-independent variables (eg, inflammatory cytokines, intestinal mucus) to identify histopathologic correlates of disease.6

In contrast to dogs, cats with IBD have endoscopic abnormalities that correlate to both clinical disease activity and histopathologic lesions at diagnosis.6

A

Standard mucosal biopsies of the stomach and duodenum alone may miss more distal sites (eg, ileal mucosa) of cellular infiltration. Ileal biopsies should be obtained in all dogs and cats to increase diagnostic yield whenever gastroduodenoscopy or colonoscopy is performed, especially as lymphoma is an important differential diagnosis in cats.36

FIGURE 5. Endoscopic images of dogs with IBD consistent with (A) increased small intestinal friability, (B) increased small intestinal granularity, and (C) intestinal mucosal erosions. (D) Endoscopic image showing the advancement of biopsy forceps to obtain partial-thickness biopsy samples in a dog with inflamed GI mucosa and IBD. Courtesy of Dr. Albert Jergens.

In cats with signs of GI disease, villous atrophy and fusion correlate with the severity of clinical signs and degree of proinflammatory cytokine upregulation in the duodenal mucosa.6 Architectural changes in the gastric mucosa correlate with cytokine upregulation in dogs with lymphocytic gastritis.51 In the colon, loss of mucus and goblet cells correlates with the severity of disease in dogs with lymphoplasmacytic and granulomatous colitis.52

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TREATMENT IBD patients with mild to moderate clinical disease activity and normal serum albumin concentrations are first treated sequentially with dietary and antibiotic trials. If they fail to respond to either of these trials, immunosuppressive therapy is initiated.

Diet A positive response to a dietary trial allows the patient’s disease to be classified as FRE, a term that includes both dietary allergy and intolerance. The primary option for a dietary trial is switching to a diet that leads to antigenic modification (eg, novel protein source, protein hydrolysate). The diet must be palatable and introduced in gradually increasing amounts over 4 to 7 days.

In dogs with FRE, a clinical response is usually observed within 1 to 2 weeks of changing the diet. In one study, dogs that responded to diet were younger and had higher serum albumin concentrations and predominant signs of large bowel diarrhea compared with dogs that did not respond to diet.33

Antibiotics An antibiotic trial typically involves administration of tylosin, oxytetracycline, or metronidazole (TABLE 2).

A positive response suggests ARD. The patient is typically maintained on antibiotics for 28 days. If signs recur after discontinuation of therapy, longterm antibiotic therapy is instituted with tylosin.

Anti-inflammatory and Immunosuppressive Therapy Patients that do not respond to a diet or antibiotic trial are usually administered prednisolone or prednisone (TABLE 2). However, as the side effects of glucocorticoids are usually more marked in largebreed dogs than in small breeds, azathioprine may be combined with glucocorticoid treatment for a faster taper period in dogs weighing >30 kg. If there is poor response to immunosuppression or a relapse is seen after tapering, cyclosporine may be considered.

In cats, chlorambucil with prednisolone is used if the response to glucocorticoid treatment is inadequate.

Hematologic parameters should be monitored regularly if chlorambucil is used. If the patient responds, then the medication can be tapered gradually, starting with the steroid, to a q48h dosing regimen.

Budesonide is a glucocorticoid medication that has been shown to be successful in the treatment of canine IBD.53,54 However, hypothalamic–pituitary– adrenal suppression and development of steroid hepatopathy has been demonstrated in dogs. Therefore, the hepatic first-pass effect of this drug in dogs may not be as beneficial as in human beings.54 An optimal dose of budesonide has not yet been determined. The response rate to budesonide has been shown to be similar to prednisone; however, this drug should be reserved for dogs that are known to respond to steroids but suffer severe

TABLE 2 Dosages of Drugs for Management of Chronic Enteropathies DRUG CLASSIFICATION

Antibiotic

Anti-inflammatory and immunosuppressant

36

DRUG

DOSAGE

Tylosin

10 to 15 mg/kg PO q8h for 28 days 5 mg/kg PO q24h, long-term

Oxytetracycline

20 mg/kg PO q8h for 28 days

Metronidazole

10 mg/kg PO q12h for 28 days

Prednisolone

2 mg/kg PO q24h for 2 weeks, then tapered over 6−8 weeks

Cyclosporine

5 mg/kg PO q24h for 10 weeks 5 to 10 mg/kg PO q24h

Chlorambucil

2 to 6 mg/m2 PO q24h

Budesonide

1 mg/m2 PO q24h

Sulfasalazine

20 to 50 mg/kg PO q8h for 3 to 6 weeks

CE: INFLAMMATORY BOWEL DISEASE

CONTINUING EDUCATION

side effects.53 Some dogs still develop side effects of steroid administration while on budesonide, and owners should be warned about this.

Sulfasalazine and related drugs are often used in dogs when IBD is limited to the large intestine. However, because side effects include keratoconjunctivitis sicca, tear production should be monitored regularly.

Treatment of Patients With Severe PLE PLE is a recognized complication in a subset of chronic enteropathy cases, and hypoalbuminemia has been shown to be a poor prognostic indicator.33,38 Patients with albumin concentrations <1.5 g/dL are at risk of developing ascites, pleural effusion, and subcutaneous edema. Many of these patients succumb to PLE within the first 1 to 2 months of starting prednisone treatment. Some studies have shown a better outcome with single-therapy cyclosporine,55 making it a better option for many of these patients.

One recent study has shown that the combination of prednisolone and chlorambucil was superior to prednisolone and azathioprine for survival.56 Evaluation of hemostatic function in these patients is recommended to ascertain if hypercoagulability has developed as a consequence of enteric protein loss.57 Concurrent therapy with ultra-low aspirin 0.5 mg/kg PO every 24 hours or other platelet inhibitors, such as clopidogrel, is recommended in these patients to prevent thromboembolism.

In addition, elemental diets and partial parenteral nutrition may be indicated in some dogs with severe PLE. Some PLE patients can fare relatively well with dietary treatment alone, and some studies show that Yorkshire terriers with PLE may be a subgroup of solely diet-responsive dogs. In such cases, try a low-fat diet first and wait for 1 to 2 weeks before adding immunosuppressive treatment. Adequate protein content in such diets for these patients is probably even more important than fat restriction.

If in any doubt, or if the patient is already anorexic, any diet will be better than no food intake.

Finally, these patients may be at risk of complications associated with intestinal biopsy by laparotomy.

Therefore, plasma transfusion, human or canine albumin infusion, or synthetic colloid may be indicated during anesthesia for endoscopy.

Adjunctive Therapy With Probiotics The use of probiotics in people with IBD has led to some promising results, although there is still an insufficient number of large, multicenter, randomized, double-blind, placebo-controlled trials. Similarly, there has been only 1 randomized, placebo-controlled trial investigating the use of Enterococcus faecium probiotic as an adjunctive treatment in canine FRE,58 and no additional effect was demonstrated in the group of dogs receiving probiotics.

In another clinical trial, dogs with IBD were treated with the probiotic Visbiome (visbiome.com) in addition to standard treatment with immunosuppressives.

The group that received the additional daily probiotic treatment improved more than the group treated with standard therapy alone.59 It should be noted that consistent use of probiotics may have a greater association with their benefits.

PROGNOSIS FRE is highly prevalent among dogs with chronic enteropathies (at least 60% to 70%), and a favorable response to elimination or hydrolyzed diets within 2 weeks has been associated with a very good prognosis over 1 year after diagnosis.60 In these studies, the dogs were kept on the diet for at least 12 weeks after diagnosis before they were switched back to their original diet.

In a recent large retrospective study in which all dogs with chronic enteropathy were sequentially treated, only 16% were suspected to have ARD.60 All ARD dogs relapsed shortly after discontinuation of antibiotics, making long-term management of these patients difficult. An additional decisionmaking factor may be the increasing problems with antibiotic resistance in dog populations.

Also, evidence is accumulating that antibiotic treatment has long-lasting effects on the intestinal microbiome,11 which may lead to lasting dysbiosis that in itself could amplify intestinal inflammation. Many of these patients will eventually need steroids or other immunosuppressive treatments to control clinical signs.

A response to prednisone has been shown in up to 50% of dogs with chronic enteropathies.33 Other immunosuppressives can be considered if more severe disease is present or severe side effects of

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steroids are anticipated. In dogs, many steroid-refractory cases can be rescued with cyclosporine single therapy.55 Caution Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

One retrospective study demonstrated that only 26% of dogs with chronic enteropathy progress to complete remission, with intermittent clinical signs remaining in approximately one-half of cases. Furthermore, 4% were completely uncontrolled and 13% were euthanized because of poor response to treatment.38 This suggests that the prognosis of these patients can be poor.

Indications SENTINEL® SPECTRUM® (milbemycin oxime/lufenuron/praziquantel) is indicated for the prevention of heartworm disease caused by Dirofilaria immitis; for the prevention and control of flea populations (Ctenocephalides felis); and for the treatment and control of adult roundworm (Toxocara canis, Toxascaris leonina), adult hookworm (Ancylostoma caninum), adult whipworm (Trichuris vulpis), and adult tapeworm (Taenia pisiformis, Echinococcus multilocularis and Echinococcus granulosus) infections in dogs and puppies two pounds of body weight or greater and six weeks of age and older.

Dosage and Administration SENTINEL SPECTRUM should be administered orally, once every month, at the minimum dosage of 0.23 mg/lb (0.5 mg/kg) milbemycin oxime, 4.55 mg/lb (10 mg/kg) lufenuron, and 2.28 mg/lb (5 mg/kg) praziquantel. For heartworm prevention, give once monthly for at least 6 months after exposure to mosquitoes.

Finally, the main negative prognostic indicator for chronic enteropathy in dogs has been identified as hypoalbuminemia.33,38 More prospective treatment trials are necessary, especially in severely affected and hypoproteinemic animals, to improve long-term survival in these cases.

Dosage Schedule Praziquantel per Number of chewable chewables

Milbemycin Oxime per chewable

Lufenuron per chewable

2 to 8 lbs.

2.3 mg

46 mg

22.8 mg

One

8.1 to 25 lbs.

5.75 mg

115 mg

57 mg

One

25.1 to 50 lbs.

11.5 mg

230 mg

114 mg

One

50.1 to 100 lbs.

23.0 mg

460 mg

228 mg

One

Body Weight

Over 100 lbs.

To see the references for this article, please visit tvpjournal.com.

Administer the appropriate combination of chewables

Kayode Garraway

Precautions Treatment with fewer than 6 monthly doses after the last exposure to mosquitoes may not provide complete heartworm prevention.

Kayode Garraway, DVM, received his veterinary degree from St. George’s University College of Veterinary Medicine, with his clinical year completed at North Carolina State University College of Veterinary Medicine. He did a small animal rotating internship at the University of Tennessee College of Veterinary Medicine, followed by a specialty internship in internal medicine and critical care at Gulf Coast Veterinary Specialists in Houston, Texas. He is currently in his third year of residency in small animal internal medicine at Iowa State University College of Veterinary Medicine. He is also currently completing a master’s degree in veterinary clinical sciences and is an adjunct instructor at Iowa State University. His interests include small animal gastroenterology and immunology.

Prior to administration of SENTINEL SPECTRUM, dogs should be tested for existing heartworm infections. At the discretion of the veterinarian, infected dogs should be treated to remove adult heartworms. SENTINEL SPECTRUM is not effective against adult D. immitis.

Karin Allenspach

To ensure adequate absorption, always administer SENTINEL SPECTRUM to dogs immediately after or in conjunction with a normal meal.

SENTINEL SPECTRUM may be offered to the dog by hand or added to a small amount of dog food. The chewables should be administered in a manner that encourages the dog to chew, rather than to swallow without chewing. Chewables may be broken into pieces and fed to dogs that normally swallow treats whole. Care should be taken that the dog consumes the complete dose, and treated animals should be observed a few minutes after administration to ensure that no part of the dose is lost or rejected. If it is suspected that any of the dose has been lost, redosing is recommended.

Contraindications There are no known contraindications to the use of SENTINEL SPECTRUM. Warnings Not for use in humans. Keep this and all drugs out of the reach of children.

Mild, transient hypersensitivity reactions, such as labored breathing, vomiting, hypersalivation, and lethargy, have been noted in some dogs treated with milbemycin oxime carrying a high number of circulating microfilariae. These reactions are presumably caused by release of protein from dead or dying microfilariae.

Karin Allenspach, DVM, PhD, DECVIM-CA, received her veterinary degree from the University of Zurich. She did an internship in small animal emergency medicine and critical care at Tufts University School of Veterinary Medicine and a residency in small animal internal medicine at the University of Pennsylvania School of Veterinary Medicine. She was awarded a PhD in veterinary immunology from the University of Bern, Switzerland, for her work on canine chronic enteropathies. She is a board-certified internist and currently appointed as professor in small animal medicine at Iowa State University.

Do not use in puppies less than six weeks of age.

Do not use in dogs or puppies less than two pounds of body weight.

The safety of SENTINEL SPECTRUM has not been evaluated in dogs used for breeding or in lactating females. Studies have been performed with milbemycin oxime and lufenuron alone.

Adverse Reactions The following adverse reactions have been reported in dogs after administration of milbemycin oxime, lufenuron, or praziquantel: vomiting, depression/lethargy, pruritus, urticaria, diarrhea, anorexia, skin congestion, ataxia, convulsions, salivation, and weakness.

To report suspected adverse drug events, contact Virbac at 1-800-338-3659 or the FDA at 1-888-FDA-VETS.

Albert Jergens

Information for Owner or Person Treating Animal Echinococcus multilocularis and Echinococcus granulosus are tapeworms found in wild canids and domestic dogs. E. multilocularis and E. granulosus can infect humans and cause serious disease (alveolar hydatid disease and hydatid disease, respectively).

Owners of dogs living in areas where E. multilocularis or E. granulosus are endemic should be instructed on how to minimize their risk of exposure to these parasites, as well as their dog’s risk of exposure. Although SENTINEL SPECTRUM was 100% effective in laboratory studies in dogs against E. multilocularis and E. granulosus, no studies have been conducted to show that the use of this product will decrease the incidence of alveolar hydatid disease or hydatid disease in humans. Because the prepatent period for E. multilocularis may be as short as 26 days, dogs treated at the labeled monthly intervals may become reinfected and shed eggs between treatments.

Albert Jergens, DVM, MS, PhD, DACVIM (SAIM), received his veterinary degree from Texas A&M College of Veterinary Medicine. He completed a residency in small animal internal medicine at the University of Missouri-Columbia College of Veterinary Medicine. He was awarded a PhD in immunology from Iowa State University, where he is currently a board-certified internist in small animal internal medicine. His clinical interests include gastroenterology, gastrointestinal endoscopy, and hostmicrobiota interactions mediating gastrointestinal health and disease.

Manufactured for: Virbac AH, Inc. P.O. Box 162059, Ft. Worth, TX 76161 NADA #141-333, Approved by FDA © 2015 Virbac Corporation. All Rights Reserved.

SENTINEL and SPECTRUM are registered trademarks of Virbac Corporation.

02/15

38

CE: INFLAMMATORY BOWEL DISEASE

FRIENDS

LIFE

Year-round parasite protection is the key to a lasting friendship.

Prevention. Protection.

POWERED BY LUFENURON.

The only 6-in-1 parasite protection

POWERED BY LUFENURON. Broad-spectrum protection Powerful flea prevention Built for compliance

1

To order, contact your distributor or call your Virbac representative at 1-844-4-VIRBAC (1-844-484-7222).

Important Safety Information for SENTINEL® SPECTRUM® (milbemycin oxime/lufenuron/praziquantel): Dogs should be tested for heartworm prior to use. Mild hypersensitivity reactions have been noted in some dogs carrying a high number of circulating microfilariae. Treatment with fewer than 6 monthly doses after the last exposure to mosquitoes may not provide complete heartworm prevention. For complete product information, refer to the product insert. To obtain a package insert, contact Veterinary Technical Product Support at 1-800-338-3659, or visit us.virbac.com.

Reference: 1. Data on file, Vetstreet Data Analytics. Virbac Corporation.

© 2017 Virbac Corporation. All Rights Reserved. SENTINEL and SPECTRUM are registered trademarks of Virbac Corporation. 12/17 18000

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Inflammatory Bowel Disease in Dogs and Cats LEARNING OBJECTIVES

By reading this article, participants will acquire a better knowledge base of the known pathogenesis of, and common clinical signs associated with, inflammatory bowel disease (IBD). Readers will also be able to methodically consider the differential diagnoses and diagnostic testing for chronic enteropathies, recognize when it may be best to refer for additional diagnostics, and establish an appropriate treatment plan.

OVERVIEW

This article provides an overview of the factors involved in canine and feline IBD, including the genetic, immune, environmental, and gastrointestinal interactions, as well as clinical findings, diagnosis, treatment options, and prognosis.

1. What is/are the most common cell infiltrate(s) within the lamina propria in IBD? a. Macrophages b. Eosinophils c. Neutrophils d. Lymphocytic and plasmacytic 2. Boxers and French bulldogs are suspected to have a predisposition for which chronic enteropathy? a. Histiocytic ulcerative colitis b. Lymphangiectasia c. Inflammatory bowel disease d. Immunoproliferative enteropathy 3. In German shepherds with IBD, there is thought to be single nucleotide polymorphisms in which Tolllike receptor (TLR)? a. TLR 3 b. TLR 4 c. TLR 8 d. TLR 9 4. The pathogenesis IBD is thought to be multifactorial; suspected etiologies include all of the following except: a. Genetics b. Dysbiosis c. Deficiencies in immune tolerance d. Immunosuppressive therapies 5. Which biochemical finding in dogs correlates with a negative outcome in IBD? a. Elevated alanine aminotransferase b. Elevated creatine kinase c. Hypokalemia d. Hypoalbuminemia

The article you have read has been submitted for RACE approval for 1 hour of continuing education credit and will be opened for enrollment when approval has been received. To receive credit, take the approved test online for free at vetfolio.com/journal-ce.

Free registration on VetFolio.com is required. Questions and answers online may differ from those below.

Tests are valid for 2 years from the date of approval.

6. Deficiency of ________ should always be corrected in IBD patients, as failure to correct the deficiency can delay clinical improvement. a. Cobalamin b. Magnesemium c. Calcium d. Folate 7. Confirmation of a diagnosis of IBD involves which specific diagnostic test? a. Complete blood count b. Ultrasound with fine needle aspiration c. Endoscopy with histopathologic review of biopsy samples d. Serum chemistry 8. A positive response to a dietary trial with a hydrolysate or novel protein involves improvement within ______ weeks. a. 1 to 2 b. 4 to 6 c. 8 to 10 d. 12 to 15 9. In dogs with IBD refractory to prednisone therapy, which rescue immunosuppressive therapy has shown some proven beneficial response? a. Leflunomide b. Chlorambucil, single-drug therapy c. Azathioprine, single-drug therapy d. Cyclosporine 10. In cats, which combination of medications has shown successful control of IBD? a. Prednisone and cyclosporine b. Prednisolone and chlorambucil c. Prednisolone and mycophenolate d. Prednisolone and cyclosporine

NOTE Questions online may differ from those here; answers are available once CE test is taken at vetfolio.com/journal-ce. Tests are valid for 2 years from date of approval.

40

CE: INFLAMMATORY BOWEL DISEASE

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To learn more, please visit www.CYTOPOINT.com Indication: CYTOPOINT aids in the reduction of clinical signs associated with atopic dermatitis in dogs. *Repeat administration every 4 to 8 weeks, as needed, in individual patients.1

References: 1. Data on file, Study Report No. C863R-US-12-018, Zoetis Inc. 2. Gonzales AJ, Humphrey WR, Messamore JE, et al.

Interleukin-31: its role in canine pruritus and naturally occurring canine atopic dermatitis. Vet Dermatol. 2013;24(1):48-53. doi:10.1111/j.1365-3164.2012.01098.x. 3. Data on file, Study Report No. C362N-US-13-042, Zoetis Inc. 4. Data on file, Study Report No. C961R-US-13-051, Zoetis Inc. All trademarks are the property of Zoetis Services LLC or a related company or a licensor unless otherwise noted. Š 2017 Zoetis Services LLC. All rights reserved. CYT-00097R1

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CE: CANINE ATOPIC DERMATITIS

CONTINUING EDUCATION

CONTINUING EDUCATION

DERMATOLOGY

Canine Atopic Dermatitis: Updates on Diagnosis and Treatment Frane Banovic, DVM, PhD, DECVD University of Georgia College of Veterinary Medicine

Canine atopic dermatitis (CAD) is a common skin disorder defined as a hereditary predisposition to develop pruritic inflammatory skin disease associated with IgE antibodies, which typically target environmental allergens.1 The disease typically affects dogs age 6 months to 3 years and is characterized by pruritus and secondary skin lesions of a characteristic distribution around the face (mouth, eyes), concave aspect of the ear pinnae, ventral abdomen, flexor aspects of elbow, carpal, and tarsal joints, interdigital skin, and perineal area (FIGURES 1 AND 2).1

FIGURE 1. A French bulldog with an acute flare of atopic dermatitis and secondary superficial staphylococcal folliculitis on abdomen. This dog exhibits patches of erythema and edema with excorations on both axillae.

The initial clinical signs of CAD are those associated with pruritus (eg, scratching, rubbing, chewing, excessive grooming or licking); erythema and papules may also be present. Depending on the allergens involved, clinical signs are seasonal or, most commonly, nonseasonal.1

CLEAN SLATE Topical once- to twice-weekly therapy using antimicrobial shampoos (eg, chlorhexidine, benzoyl peroxide, miconazole, ketoconazole) and ear cleansers are recommended as an essential component in the long-term management of secondary infected CAD.

FIGURE 2. A chronic atopic dermatitis case with secondary Malassezia dermatitis. Skin lesions feature severe erythema; alopecia; excoriations; and lichenification of axillae, ventral abdomen, perineal area, and caudomedial thighs.

shutterstock.com/textu

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PATHOGENESIS The pathogenesis of CAD is complex. Percutaneous sensitization to environmental allergens (eg, dust mites, pollen, mold) and/or allergens from food induces skin infiltration by various inflammatory cells, activation of resident cells, and local production of inflammatory/itch mediators.1,2 Several factors can exacerbate CAD (FIGURE 3),1-3 such as: ■■ Ectoparasites,

particularly fleas

■■ Environmental

factors (eg, increase in seasonal allergen)

■■ Cutaneous

colonization/infection by bacteria (Staphylococcus pseudintermedius) and yeast (Malassezia pachydermatis)

■■ Epidermal

implemented to help veterinarians interpret clinical findings when confronted with an itchy dog.7 These criteria were developed from a large case series of confirmed cases of CAD. Complex statistical analysis was used to identify a set of clinical features that had maximum association with CAD. However, these criteria have a sensitivity and specificity of about 80% when 5 of 8 are fulfilled. This means that using them as the sole “diagnostic test” would lead to a wrong diagnosis in every fifth dog.1,7 Therefore, they should be applied concurrently with a careful workup for exclusion of diagnostic differentials, such as ectoparasitic diseases and skin infections.

When they are used in this way, the specificity of diagnosis can be expected to increase markedly.

barrier dysfunction

UPDATE ON DIAGNOSIS Despite significant efforts to identify a “diagnostic test” for CAD, the diagnosis remains clinical. It is based on the following:

BOX 1 Important Details in History of Dogs Suspected of Having CAD 

Age at onset

■■ History (BOX 1)



Seasonality of clinical signs

■■ Characteristic



Pruritus with no skin changes (pruritus sine materia) at onset



Familial or breed predisposition (eg, West Highland white terrier, Golden or Labrador retriever, German shepherd, Boxer, French bulldog, bull terrier, shar-pei)3,4



Previous response to glucocorticoids

4,5

clinical criteria (BOX 2)

■■ Exclusion

of other diseases with a similar clinical presentation1,3,6

Clinical Criteria Recently, a new set of criteria for CAD diagnosis, known as Favrot’s criteria (BOX 2), has been

CAD

BOX 2 Favrot’s Criteria 1. Onset of signs under 3 years of age 2. Dog living mostly indoors 3. Glucocorticoid-responsive pruritus 4. Pruritus sine materia at onset (ie, alesional pruritus)

Mites Pollens Molds

Foods

Fleas

Bacteria Yeast

6. Affected ear pinnae 7. Nonaffected ear margins 8. Nonaffected dorsolumbar area

FIGURE 3. Flare factors involved in pathogenesis of CAD.

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5. Affected front feet

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Exclusion of Other Diseases Regardless of the history and criteria, CAD should never be diagnosed until diseases that resemble it, such as flea allergy dermatitis, ectoparasitic disease (eg, sarcoptic mange, cheyletiellosis, pediculosis, trombiculiasis, and otoacariasis), and primary skin infections have been ruled out.

The initial steps of a basic workup to rule out ectoparasites are flea combing, skin scraping, hair plucking, and cytologic examination of skin and ear samples. Skin lesions and pruritus associated with flea allergy dermatitis are most common at the lumbosacral area, tail base, and caudomedial thighs,6 which are not commonly affected areas in CAD. Patients with CAD exhibit frequent, sometimes recurrent, staphylococcal and yeast skin infections, which can exacerbate pruritus and dermatitis;6 therefore, patients predisposed to secondary skin infection should be considered and screened for CAD. Skin biopsy results are usually nonspecific and inadequate for diagnosing CAD.6 However, in some cases, skin biopsy may be indicated to rule out a diagnostic differential, such as cutaneous lymphoma (FIGURE 6).6 Cutaneous epitheliotrophic T-cell lymphoma may present with pruritus, excessive scales, and generalized erythema in dogs and may mimic atopic dermatitis lesions.8

Intradermal and IgE Testing Allergy testing, which includes serologic evaluation of allergen-specific IgE and intradermal skin testing, should not be used for the diagnosis of CAD.6 Many healthy dogs are sensitized to environmental allergens and consequently have positive test results.

Furthermore, many dogs with clinical signs of CAD have negative results on these tests; the term atopiclike dermatitis describes this group of dogs.1,9 Allergy testing should be carried out only to identify allergens to be used for allergen-specific immunotherapy and desensitization (see Allergen Immunotherapy).

UPDATES ON TREATMENT CAD is a multifactorial chronic disease that requires a multimodal treatment approach to decrease pruritus and inflammation below the threshold of clinical signs. Guidelines from the International Task Force on Canine Atopic Dermatitis1,3 recommend therapeutic interventions based on identifying and managing the flare factors (FIGURE 3), as

well as whether the patient is experiencing an acute flare or has chronic skin lesions.

A rational approach to treatment is required; the keys to success are client education and a combination of interventional measures specific for flare factors and symptomatic treatment.

The management of each patient starts with: 1. Identifying and addressing (or, if possible, avoiding) the associated flare factors (FIGURE 4) 2. Using a topical and/or systemic treatment to decrease inflammation and pruritus

Management of Flare Factors Specific avoidance interventions depend on identification of all the factors associated with a flare for clinical signs in an individual dog. Common flare factors include fleas and fleabite hypersensitivity, bacterial or yeast overgrowth, and food and environmental allergens. CAD due to food and environmental allergens can present with identical clinical signs and may, in fact, be a concurrent problem.

Fleas and Fleabite Hypersensitivity Dogs with CAD are predisposed to fleabite hypersensitivity if exposed repeatedly to flea salivary antigens.10 As a result, all dogs with CAD should be protected with year-round flea adulticides combined with relevant environmental measures. Some dogs may present with concurrent clinical signs of CAD (eg, licking feet, ear infections) and fleabite hypersensitivity (eg, pruritus and hot spots in tail base area); these patients need aggressive flea treatment as well as environmental measures.1 Bacterial or Yeast Overgrowth Specific antibacterial/antifungal interventions should be based on regular cytologic evaluation (impression smears, tape) of atopic skin lesions and documented presence of bacteria/yeast at these sites.

Because atopic patients frequently develop recurrent ear and skin infections with Staphylococcus and Malassezia species (FIGURE 5), topical once- to twice-weekly therapy using antimicrobial shampoos (eg, chlorhexidine, benzoyl peroxide, miconazole, ketoconazole) and ear cleansers are recommended as an essential component in the long-term management of secondary infected CAD. The widespread emergence of multidrug-resistant

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S pseudintermedius-associated pyoderma in dogs has increased interest in targeted topical antimicrobial therapy with chlorhexidine shampoos and sprays.11 More severe or generalized cases of pyoderma may require first-line systemic antimicrobials (BOX 3); bacterial culture and susceptibility testing may be needed in cases of recurrent pyoderma.12 For Malassezia dermatitis, there is evidence for use of topical miconazole/chlorhexidine shampoo treatment (Malaseb, bayerdvm.com; twice a week for 3 weeks) and, in severe cases, systemic treatments with azole derivatives (BOX 3). Many drug interactions exist with use of azole drugs, especially with ketoconazole.13 Frequent use of systematic antimicrobials (antibiotics and antifungals) is not recommended because it is likely associated with increased prevalence of drug resistance.

BOX 3 Systemic Antimicrobial Options for Severe Skin Infection Pyoderma 

Cephalexin, cefadroxil 15-30 mg/kg PO q12h



Cefpodoxime 5-10 mg/kg PO q24h



Clindamycin 5.5-11 mg/kg PO q12h



Lincomycin 15-25 mg/kg PO q12h

Malassezia dermatitis 

Ketoconazole 5-10 mg/kg q24h



Itraconazole 5 mg/kg q24h for 3 weeks



Terbinafine 30 mg/kg q24h for 3 weeks

A

B

C

D

FIGURE 4. A 6-year-old mixed-breed dog with CAD and flea allergy dermatitis with severe pruritus and secondary bacterial infection at initial presentation (A, C). After failed allergen-specific immunotherapy, treating fleas and resolving secondary infection, the dog’s allergies became well controlled with frequent medicated baths and lokivetmab, anti–canine IL-31 monoclonal antibody (B, D).

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Food-induced CAD The Task Force on Canine Atopic Dermatitis recognizes some controversy regarding the association between food and CAD—some dogs with CAD exhibit flares when exposed to food allergens.

Such patients likely have recurrent, year-round clinical signs and sometimes have additional gastrointestinal signs (soft stools, vomiting, diarrhea, increased fecal frequency). All dogs with nonseasonal CAD should undergo 1 or more dietary restriction-provocation trials to determine whether food allergens contribute to clinical signs.1,3 The current “gold standard” method for identifying food allergy in animals is to observe improvement of CAD clinical signs when the animal is fed a

novel protein diet followed by recurrence of clinical signs when rechallenged with a previously fed food.14,15 The novel protein is usually combined with a carbohydrate and is fed as a home-cooked or commercial diet (BOX 4).16-18 Commercial novel protein source diets typically include proteins from venison, rabbit, duck, kangaroo, ostrich, or emu and are combined with a carbohydrate source, such as potatoes, sweet potatoes, rutabagas, oats, or barley.

The novel diet is required for a minimum of 6 weeks, although some cases may continue to improve for up to 8 to 10 weeks.1,3,19 Additional clinical signs, such as severe skin inflammation, pruritus, ear infections, and superficial pyodermas, influence the length of time required to feed the diet. Furthermore, most dogs with food allergies have additional hypersensitivities, such as

A

B

C

D

FIGURE 5. (A, C) Skin lesions of superficial canine pyoderma on thorax of atopic dog and skin cytology revealing neutrophils and extracellular and intracellular cocci. (B, D; x100 magnification for C) Malassezia dermatitis affecting ventral abdomen of a dog with CAD and associated tape skin cytology revealing peanut-shaped yeast (x100 magnification for D).

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CONTINUING EDUCATION

environmental or flea allergies, that could fluctuate daily or seasonally and complicate the length of a food trial.

To avoid gastrointestinal upset in the first few days of introduction and rechallenge, my clinical experience suggests initially mixing the old and new food (50%/50%) before complete transition to new or old food.

Adjunctive treatments for severe skin inflammation, pruritus, ear infections, and superficial pyoderma

BOX 4 Considerations for Diet Trials The closer the taxonomic relationship between meat sources, the higher the risk for immunologic cross-reactivity between proteins.16 In vitro, allergens from chicken, can cross-react with those from other poultry; identical cross-reactivity exists for beef and other ruminant proteins.16 As the variety of protein sources available in commercial pet foods has expanded and the habit of feeding table scraps has increased, the choice of novel protein sources has become more limited.

Hydrolyzed protein diets are used for the diagnosis and management of dogs with food allergies; in these diets, enzymatic hydrolysis is used to convert native proteins into small peptides that are less likely to be allergenic.15 However, two recent studies found that dogs allergic to soy and chicken experienced flares when fed a hydrolyzed soy or chicken diet.17 Additionally, in a recent randomized, double-blinded, crossover trial, a hydrolyzed poultry feather diet did not induce pruritus flares in any of 10 dogs with chicken-induced pruritic food allergy, whereas several dogs had flares after eating a hydrolyzed chicken liver diet.17 Hydrolysate-containing diets are probably best used in dogs with no suspected hypersensitivity to the original source of hydrolyzed peptides.

Diet trials should never be performed with â&#x20AC;&#x153;pet store brandâ&#x20AC;? diets because these diets often contain trace amounts of important allergens not listed on the label.18 Many flavored medications (chewable heartworm prophylactics, flavored antibiotics, and vitamin tablets), especially over-the-counter medications, may contain unwanted/ hidden proteins. All flavored medication should therefore be avoided, including medication packaged in gelatin capsules.

Regardless of the diet chosen, compliance is paramount and strict adherence to the prescribed food is necessary.

should be initiated immediately at the start of a diet trial. The treatment should resolve all concurrent clinical signs of pruritus and infection (ears, skin) within 6 to 10 weeks of the diet trial, at which time the symptomatic medications are discontinued, and the patient can be maintained only on the novel food for the following 2 to 3 weeks. The patients are carefully observed during these 2 to 3 weeks; if the clinical signs or pruritus and skin/ear infections do not recur, the patient should be rechallenged with the old diet. A relapse of clinical signs within 14 days of rechallenge is expected in dogs with food allergy, although in most cases, untrained client/ owner observation is used to determine relapse.1,3 Environment-Induced CAD

Allergen Control The most common causes of CAD in my practice are environmental allergens from dust mites and pollens. House dust mite glycoproteins are likely the most common allergens in atopic dogs; therefore, reducing the numbers of mites and their allergens in the household may help alleviate CAD signs.1,3 Several products are marketed for dust mite allergen reduction; however, only a single uncontrolled study showed the benefit of house dust mite control with an acaricide benzyl benzoate spray (Acarosan Spray, bissell.com) for reduction of clinical signs of CAD in mite-hypersensitive atopic dogs.20 Additional controlled studies correlating dust mite allergen reduction and clinical improvement in atopic dogs are needed; these studies should span several months because of the long persistence of mite allergens in the environment. Another measure to theoretically reduce mite allergens involves frequent and thorough pet mattress and environment washing and vacuuming.

Allergen immunotherapy The sole causal treatment for environment-induced CAD is allergen immunotherapy (AIT), also known as desensitization or hyposensitization.1,3 AIT consists of administering gradually escalating quantities of relevant allergens subcutaneously or sublingually (BOX 5)21-27 until immunologic tolerance to the allergens is established and relapses of CAD clinical signs are prevented.

Molecular and cellular mechanisms of AIT include early mast cell and basophil desensitization effects; an induction of interleukin-10-secreting inducible regulatory T and B cells; regulation of IgE and IgG4 production; and inhibition of responses from JANUARY/FEBRUARY 2018

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eosinophils, mast cells, and basophils in the affected tissues.21 Rationally, allergens likely to contribute to CAD can be identified by using an intradermal test or serum IgE serology. In vivo challenge by intradermal allergen injection is considered the gold standard; this assay provides functional evidence of hyperreactivity within atopic skin. Results of in vitro assessments of allergen-specific IgE (serum allergy testing) vary between laboratories, and no standardization exists for this test.28

BOX 5 Subcutaneous versus Sublingual Allergen Immunotherapy Subcutaneous immunotherapy has been a mainstay of AIT in dogs with CAD for decades, mainly because systemic adverse effects (eg, life-threatening anaphylaxis) are very rare compared with occurrence in human patients.1,21 However, subcutaneous AIT in dogs lacks protocol standardization (eg, amount of allergen extract, frequency of administration, administration of purified or recombinant allergen). Two recent trials using a high-dose recombinant house dust mite allergen prevented allergen-induced skin lesions in experimentally sensitized atopic dogs22 and reduced clinical scores in dust mite–sensitized naturally atopic dogs. 23 These observations warrant further larger randomized controlled trials using highly purified or recombinant major allergens for AIT in atopic dogs.

Recently, sublingual AIT, in which allergen extracts are administered in the oral cavity instead of by injection, has emerged as another immunotherapy treatment for allergic diseases in humans. 24 Sublingual AIT reduces the risk for severe systemic reactions observed in humans receiving subcutaneous AIT; in dogs, however, it requires long-term, q12h administration by the owners, which may influence client compliance.

Despite the demand for high-quality research, no consistent evidence supports the effectiveness of subcutaneous or sublingual AIT for the treatment of human atopic dermatitis. 21 Only a few studies demonstrate the efficacy of sublingual AIT in experimentally dust mite–sensitized atopic dogs. 25,26 An uncontrolled openlabel study using sublingual AIT treatment (q12h spray application) produced mild clinical improvement in 10 dogs with dust mite–associated natural CAD; a formulation and dosing schedule equivalent to a commercial product (Heska Allercept Therapy Drops, heska.com) were applied. 27

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Although AIT is not effective in every atopic dog, within 12 months approximately 50% and 80% of dogs with CAD exhibit an improvement in clinical signs and/or a decrease in use of symptomatic medications, respectively.1,3 Antiinflammatory/anti-itch drugs should be given temporarily during AIT administration and individually tailored to maintain a good quality of life until AIT is judged to be effective.

Management of Inflammation and Pruritus Many cell types contribute to the complex immune network underlying cutaneous inflammation in CAD.1,2 After activation, these cells up- or downregulate various modulators, cytokines, and chemokines that promote pathology in food- and environment-induced CAD skin lesions. Several drugs are effective in modulating these cells and mediators in food- and environment-induced CAD (TABLE 1). Symptomatic intervention in dogs with food-induced atopic disease should resolve clinical signs within 6 to 10 weeks of a diet trial, whereas patients with environmentinduced CAD may experience recurrent flares throughout the year, requiring long-term control.

The guidelines from the International Task Force on Canine Atopic Dermatitis1,3 base therapeutic recommendations for pruritus and skin inflammation interventions on whether the patient is experiencing an acute flare or has chronic skin lesions. This distinction can be confusing because most atopic dogs present with a wide spectrum of clinical phenotypes involving chronic pruritus and/or skin lesions ranging from acute erythematous papules to chronic lichenified plaques. As a simple rule of thumb, the management of CAD should focus on: 1. Inducing remission (“get control”) and 2. Initiating long-term management for prevention of flares (“keep control”) An example of this approach is daily, intensive systemic and topical glucocorticoid administration for a few weeks until clinical signs are resolved (“get control”), followed by only intermittent topical glucocorticoids twice weekly to previously affected areas, with a goal of suppressing subclinical inflammation (“keep control”).

Topical therapy aimed at improving epithelial barrier dysfunction may also be appropriate (BOX 6).

PEER REVIEWED

TABLE 1 Highly Effective Drugs for Remission and Management of Canine Atopic Dermatitis INDUCING REMISSION: “GET CONTROL”

LONG-TERM MANAGEMENT: “KEEP CONTROL”

Oral and/or topical glucocorticoids

Oral and/or topical glucocorticoids

Oclacitinib

Cyclosporine

Lokivetmab

Lokivetmab

Surgery

Oclacitinib

Oral and Topical Glucocorticoids Glucocorticoids are fast-acting medications that deactivate many inflammatory cells and reduce inflammatory/itch mediators. They are used for both inducing remission and maintaining long-term control in CAD. Unfortunately, prolonged systemic use is associated with polyuria, polydipsia, polyphagia, muscle and skin atrophy, bacterial and fungal infections, demodicosis, and iatrogenic hyperadrenocorticism.1,29-31 Topical steroids are the mainstay of therapy for bringing localized CAD skin lesions under remission; medium-potency glucocorticoid sprays, such as triamcinolone acetonide (Genesis, us.virbac.com) and a diester hydrocortisone aceponate (Cortavance, us.virbac.com), show high efficacy in CAD.3 The triamcinolone acetonide and hydrocortisone aceponate sprays are currently unavailable in the United States; however, another highly potent diester steroid, mometasone furoate, is available as a cream through pharmacies and is widely used in my practice.

As suggested for human atopic dermatitis, daily application of steroids for 2 to 4 weeks to clear localized skin lesions should be followed with the intermittent use of the same product (eg, 2 to 3 times per week) on the previously affected skin even if visible lesions have disappeared. This “proactive treatment” approach reduces the risk for flares and extends the time of remission in humans32 and dogs33,34 compared with reactive therapy (ie, therapy only when clinical signs are visible). Even though mometasone furoate and hydrocortisone aceponate induce mild dermal degradation through inhibition of collagen I and III propeptides, no visible skin atrophy has been observed in CAD skin lesions during long-term intermittent topical application.33-35 If CAD signs are too extensive to be controlled with only topical formulations, then short-acting oral glucocorticoids are recommended in conjunction

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with topical steroids.3 Prednisone/prednisolone (0.5 to- 1 mg/kg PO) or methylprednisolone (0.4 to- 0.8 mg/kg PO) should be administered q24h or divided into 2 doses for 5 to 15 days, then reduced or discontinued as signs decrease based on patient response. To reduce the adverse effects and dose of oral glucocorticoids in some allergic dogs, the glucocorticoid-antihistamine combination Temaril-P (trimeprazine 5 mg/prednisolone 2 mg, zoetis.com) can be effectively used; the antihistamine trimeprazine seems to potentiate the low dose of prednisolone, achieving a steroid-sparing effect.36

BOX 6 Improving Epidermal Barrier Dysfunction The complex process of epidermal differentiation is disturbed in CAD lesions, and the impaired skin barrier offers potential targets for therapeutic intervention, such as fatty acids (oral supplements or topical solutions) and various topical treatments. Weekly bathing with a mild nonirritating shampoo and postbathing topical moisturizers are recommended for each patient; this therapy provides a direct soothing effect to the skin, physically removes surface allergens, and increases skin hydration.1,5 According to the systematic review of clinical trials, essential fatty acid supplementation is indicated only for long-term management of CAD as an adjunctive treatment; the clinical benefit of essential fatty acid supplements on the skin may take up to 2 months to be seen.1,5 In recent years, some topical (spot-on, spray, shampoo, emulsion) formulations containing fatty acids and ceramides have been introduced for dogs with CAD; however, their efficacy is inconsistent, and veterinarians should weigh their benefit and cost before pdeciding to use them. 5

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Steroid-Sparing Agents Medications that may help avoid adverse effects associated with long-term systemic glucocorticoids are also available for dogs with CAD.

Oclacitinib Oclacitinib (Apoquel, zoetis.com) is the first Janus kinase (JAK) inhibitor approved in the United States and Canada for the treatment of atopic dermatitis in dogs.37 JAKs are nonreceptor tyrosine kinases activated by various cytokine receptors and regulate the expression of multiple inflammatory genes. JAK inhibition may modulate the immune response to varying degrees, ranging from selective inhibition of cytokine production with anti-inflammatory effects to broader inhibition of cytokine production resulting in immunosuppression.

Four JAK families of enzymes (JAK1, JAK2, JAK3, and tyrosine kinase 2) exist in mammals, and different inhibitors target different families.38 At this time, oclacitinib is considered to be a selective JAK1 inhibitor, and as such it is proposed to be an anti-itch agent without being immunosuppressive.38 However, safety studies performed in 6- and 12-monthold dogs with high oclacitinib dosages resulted in adverse effects, suggesting that this drug has potential immunosuppressive properties in dogs (US Food and Drug Administration [FDA] data39). A recent study used an integrated modeling approach using isolated canine T cells; the results revealed that oclacitinib appears to have immunosuppressive properties, but only at dosages above those used to treat allergic pruritus in dogs.40 Oclacitinib (0.4 to 0.6 mg/kg q12h for 14 days, then q24h as needed) is considered a safe, fast-acting, well-tolerated oral drug with good efficacy for inducing remission and long-term control of CAD in dogs at least 12 months old. It has a very rapid onset of action for itch and a slower one for skin inflammation. Its immunosuppressive properties during in vivo administration are unknown, and opportunistic infections (eg, viral papillomas) or infestations (eg, demodicosis) might develop in susceptible individuals. In these cases, oclacitinib should be discontinued until the infection/infestation clears or is treated adequately; other anti-itch/inflammation drugs may be used for control of CAD in these patients.

Two recent studies indicated that routine hematologic evaluation, serum chemistry, and urine culture are not indicated for dogs receiving oclacitinib up to 630 days; however, clinicians should decide on monitoring in each case on the basis of clinical signs.37,41

Cyclosporine Oral cyclosporine is a calcineurin inhibitor that, at low doses, exerts an anti-inflammatory and immunomodulatory effect through inhibition of T-cell activation.42 Cyclosporine is approved for the longterm control of CAD at the starting oral dose of 5 mg/kg q24h for at least 6 to 8 weeks because clinical benefit has slow onset; the full benefit of this drug is usually observed after 8 weeks of administration.1,3,43 Oral steroids43 or oclacitinib44 can be administered concurrently in the first 3 to 4 weeks to overcome the slow onset of clinical effect; a recent study showed that the administration of oral prednisolone (1 mg/kg q24h for 7 days then q48h for 14 days) with cyclosporine at 5 mg/kg led to a rapid reduction in pruritus and skin lesions. In patients with good response to cyclosporine, the long-term dose and/ or frequency are adjusted as needed for therapeutic effect.

Vomiting and diarrhea are seen in 30% of patients but are usually self-limiting within the first 7 to 10 days; administration with food or freezing the cyclosporine capsules may help decrease gastrointestinal upset.42 As with many immunosuppressive drugs, opportunistic infections (eg, fungal infections) may develop in susceptible individuals receiving cyclosporine.45 A retrospective study evaluated the frequency of urinary tract infection and recommended routine urine cultures for dogs receiving long-term cyclosporine; however, some dogs in this study may have had subclinical infections before cyclosporine administration.46 Less commonly reported dermatologic adverse effects include gingival hyperplasia, psoriasiformlichenoid-like dermatitis, and hyperplastic verrucous lesions.42 These effects usually regress with dose tapering and/or discontinuation of the cyclosporine.

Monitoring of cyclosporine levels during treatment of CAD is difficult because no significant correlation has been found between positive clinical improvement and cyclosporine blood concentration in atopic dogs; clinical response to cyclosporine remains the most reliable method of assessing efficacy in CAD.47 Microemulsified cyclosporine (Atopica, elanco.com) is approved for use in dogs with CAD in the United States; the formulation of Atopica is identical to the human formulation, Neoral (pharma.us.novartis.com).42 A human generic ultramicronized emulsified cyclosporine (Equoral, tevatxteam.com) was shown to be as effective as prednisone in reducing skin lesions and pruritus in atopic dogs,48 whereas a new

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100-mg/mL oral solution of cyclosporine (Cyclavance, Virbac, uk.virbac.com) has recently been approved in Europe for chronic clinical manifestations of atopic dermatatitis.49 A human vegetable oilbased formulation of cyclosporine (Sandimmune, pharma.us.novartis.com) shows marked intraindividual and interindividual variation in oral bioavailability in dogs and is not recommended for CAD.50

Glossary AIT allergen immunotherapy CAD canine atopic dermatitis FDA Food and Drug Administration IL-31 interleukin-31 JAK Janus kinase

Several human generic formulations of cyclosporine are listed by the FDA as being therapeutically equivalent to Neoral; these formulations have not been tested in atopic dogs for bioequivalence or therapeutic efficacy. Extreme caution is recommended with compounding preparations of cyclosporine because product quality and concentration vary markedly among cyclosporine preparations compounded for animals; as a result, a recent state-of-the-art review on cyclosporine use in companion animals discourages use of compounded cyclosporine.50

Monoclonal antibodies Biological medicine, an intervention pioneered in the last 30 years in humans, involves the use of monoclonal antibodies to target proteins, such as cellular receptors or soluble molecules, involved in disease pathogenesis.

Monoclonal antibodies are monospecific antibodies made by identical immune cells with a monovalent affinity: They bind to the same epitope (the part of an antigen that is recognized by the antibody). During the past decade, the molecular signature of human atopic dermatitis has been increasingly understood, particularly with a focus on barrier dysfunction and cutaneous/systemic immune activation, allowing development of more targeted therapies.

Recently, a monoclonal antibody capable of neutralizing canine interleukin-31 (IL-31), a cytokine

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involved in itch in dogs, was developed. Lokivetmab (Cytopoint, zoetisus.com) is approved for use in dogs in the United States.51 Injection of lokivetmab reduced the pruritic response for 3 to 4 weeks after injection without adverse effects; itch decreases within 24 to 72 hours (FIGURE 4). The effect on skin lesions was somewhat lower, with roughly half of the dogs achieving 50% reduction in skin lesions.51 The mechanism of action of lokivetmab is different from that of oclacitinib; lokivetmab binds to IL-31 before it binds to its receptor, thereby preventing the main pruritogenic effect of IL-31. Lokivetmab has the advantage of being extremely targeted. It has a very long half-life and can be safely administered with other drugs for symptomatic CAD therapy.

The label allows for repeated SC administration at a minimum of 2 mg/kg, monthly, as needed.51 Initial experience in my practice suggests lokivetmab may be best used in atopic dogs with itch but not severe skin inflammation. Furthermore, lokivetmab therapy was successful in some patients that had an insufficient response to oclacitinib.

Antihistamines H1-antihistamines (hydroxyzine, cetirizine) inhibit the action of histamine by combining with and stabilizing the inactive conformation of the H1 receptor.1,3 The current conclusion of the International Task Force on Canine Atopic Dermatitis is that there is no conclusive evidence of the efficacy of oral type-1 antihistamines for treatment of active and chronic CAD skin lesions.1,3 Veterinarians who wish to use type 1 antihistamines should limit their prescription to drugs with a demonstrable antihistamine effect in dogs (eg, hydroxyzine 2 mg/kg q12h or cetirizine 0.5 to 1.0 mg/kg q24h).1,3 REFERENCES 1. Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Vet Dermatol 2010;21:233-248.

2. Santoro D, Marsella R, Pucheu-Haston CM, et al. Review: Pathogenesis of canine atopic dermatitis: skin barrier and host-micro-organism interaction. Vet Dermatol 2015;26:84-e25.

3. Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA). BMC Vet Res 2015;11:210.

4. Picco F, Zini E, Nett C, et al. A prospective study on canine atopic dermatitis and food-induced allergic dermatitis in Switzerland. Vet Dermatol 2008;19:150-155.

5. Jaeger K, Linek M, Power HT, et al. Breed and site predispositions of dogs with atopic dermatitis: a comparison of five locations in three continents. Vet Dermatol 2010;21:118-122.

6. Hensel P, Santoro D, Favrot C, et al. Canine atopic dermatitis: detailed guidelines for diagnosis and allergen identification. BMC Vet Res 2015;11:196.

CONTINUING EDUCATION 7. Favrot C, Steffan J, Seewald W, et al. A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis.

Vet Dermatol 2010;21:23-30.

8. Fontaine J, Heimann M, Day MJ. Canine cutaneous epitheliotropic T-cell lymphoma: a review of 30 cases. Vet Dermatol 2010;21:267-275.

9. Halliwell R. Revised nomenclature for veterinary allergy. Vet Immunol Immunopathol 2006;114:2007-2008.

10. Sousa CA, Halliwell REW. The ACVD task force on canine atopic dermatitis (XI): the relationship between arthropod hypersensitivity and atopic dermatitis in the dog. Vet Immunol Immunopathol 2001;81:233-238.

11. Borio S, Colombo S, La Rosa G, et al. Effectiveness of a combined (4% chlorhexidine digluconate shampoo and solution) protocol in MRS and non-MRS canine superficial pyoderma: a randomized, blinded, antibiotic-controlled study. Vet Dermatol 2015;26:339-344.

12. Hillier A, Lloyd DH, Weese JS, et al Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases). Vet Dermatol. 2014;25:163-175.

13. Papich MG. Incompatible critical care drug combinations. In Bonagura JD (ed): Kirk’s Current Veterinary Therapy XII. Philadelphia: WB Saunders, 1995:194-198.

14. Jackson HA, Murphy KM, Tater KC, et al. The pattern of allergen hypersensitivity (dietary or environmental) of dogs with non-seasonal atopic dermatitis cannot be differentiated on the basis of historical or clinical information: a prospective evaluation 2003-2004. Vet Dermatol 2005;16:200.

Frane Banovic Frane Banovic, DVM, PhD, DECVD, is an assistant professor of dermatology at the University of Georgia College of Veterinary Medicine. After graduating from veterinary school in Zagreb (Croatia) in 2008, Dr. Banovic continued with further education at the University of Zagreb by pursuing a PhD program in veterinary microbiology. In the summer of 2011, Dr. Banovic finished a 1-year rotational internship at the Veterinary School in Munich, Germany, and started his 3-year dermatology residency program at the North Carolina State University College of Veterinary Medicine. After finishing residency, he enrolled in a postdoctoral fellowship in investigative dermatology, with a primary research focus of skin antiseptics and pathogenesis of cutaneous staphylococcal infections. He is board-certified by the European College of Veterinary Dermatology.

Dr. Banovic’s main research interests lie in the field of canine atopic dermatitis, related staphylococcal skin infections, and autoimmune skin diseases.

15. Gaschen FP, Merchant SR. Adverse food reactions in dogs and cats. Vet Clin North Am Small Anim Pract 2011;41:361-379.

16. Bexley J, Nuttall TJ, Hammerberg B, et al. Co-sensitization and crossreactivity between related and unrelated food allergens in dogs—a serological study. Vet Dermatol 2017;28:31-e7.

17. Bizikova P, Olivry T. A randomized, double-blinded crossover trial testing the benefit of two hydrolysed poultry-based commercial diets for dogs with spontaneous pruritic chicken allergy. Vet Dermatol 2016;27:289-e70.

18. Raditic DM, Remillard RL, Tater KC. ELISA testing for common food antigens in four dry dog foods used in dietary elimination trials. J Anim Physiol Anim Nutr (Berl) 2011;95:90-97.

19. Olivry T, Mueller RS, Prélaud P. Critically appraised topic on adverse food reactions of companion animals (1): duration of elimination diets.

BMC Vet Res 2015;11:225.

20. Swinnen C, Vroom M. The clinical effect of environmental control of house dust mites in 60 house dust mite-sensitive dogs. Vet Dermatol 2004;15:31-36.

21. Berings M, Karaaslan C, Altunbulakli C, et al. Advances and highlights in allergen immunotherapy: on the way to sustained clinical and immunologic tolerance. J Allergy Clin Immunol 2017 Sep 20.

22. Olivry T, Paps JS, Dunston SM. Proof of concept of the preventive efficacy of high-dose recombinant mono-allergen immunotherapy in atopic dogs sensitized to the Dermatophagoides farinae allergen Der f 2. Vet Dermatol 2017;28:183-e40.

30. Torres SM, Diaz SF, Nogueira SA, et al. Frequency of urinary tract infection among dogs with pruritic disorders receiving longterm glucocorticoid treatment. JAVMA 2005;227:239-243.

31. Gross TL, Walder EJ, Ihrke PJ. Subepidermal bullous dermatosis due to topical corticosteroid therapy in dogs. Vet Dermatol 1997;8:127-131.

32. Wollenberg A, Reitamo S, Girolomoni G, et al. Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy 2008;63:742-750.

33. Nuttall T, Mueller R, Bensignor E, et al. Efficacy of a 0.0584% hydrocortisone aceponate spray in the management of canine atopic dermatitis: a randomised, double blind, placebo-controlled trial. Vet Dermatol 2009;20:191-198.

34. Lourenço AM, Schmidt V, São Braz B, et al. Efficacy of proactive longterm maintenance therapy of canine atopic dermatitis with 0.0584% hydrocortisone aceponate spray: a double-blind placebo controlled pilot study. Vet Dermatol 2016;27:88-92.

35. Rème CA, Dufour P. Effects of repeated topical application of a 0.0584% hydrocortisone aceponate spray on skin thickness in beagle dogs. Intern J Appl Res Vet Med 2009;8:221-226.

23. Kawano K, Mizuno T. A pilot study of the effect of pullulan-conjugated Der f 2 allergen-specific immunotherapy on canine atopic dermatitis.

Vet Dermatol 2017 Aug 4.

36. Paradis M, Scott DW, Giroux D. Further investigations on the use of nonsteroidal and steroidal antiinflammatory agents in the management of canine pruritus. JAAHA 1991;27:44-48.

24. Canonica G, Cox L, Pawankar R, et al. Sublingual immunotherapy: World Allergy Organization position paper 2013 update. World Allergy Organ J 2014;7:3-52.

37. Cosgrove SB, Cleaver DM, King VL, et al. Long-term compassionate use of oclacitinib in dogs with atopic and allergic skin disease: safety, efficacy and quality of life. Vet Dermatol 2015;26:171-179.

25. Marsella R. Tolerability and clinical efficacy of oral immunotherapy with house dust mites in a model of canine atopic dermatitis: a pilot study.

Vet Dermatol 2010;21:566-571.

38. Menet CJ, Rompaey LV, Geney R. Advances in the discovery of selective JAK inhibitors. Prog Med Chem 2013;52:153-223.

26. Marsella R, Ahrens K. Investigations on the effects of sublingual immunotherapy on clinical signs and immunological parameters using a canine model of atopic dermatitis: a double-blinded, randomized, controlled study (abstract). Vet Dermatol 2012;23:66.

27. DeBoer DJ, Verbrugge M, Morris M. Clinical and immunological responses of dust mite sensitive, atopic dogs to treatment with sublingual immunotherapy (SLIT). Vet Dermatol 2016;27:82-7e23

39. US Food and Drug Administration. Apoquel. Oclacitinib Tablet.

Freedom of information summary. Original new drug application. NADA 141-345. fda.gov/downloads/AnimalV.../UCM363901.pdf Accessed November 13, 2017.

40. Banovic F, Gordon H, Tarigo J, et al. Modulatory effects of oclacitinib on in vitro canine T-cell proliferation and cytokine production (abstract).

Vet Dermatol 2017. doi: 10.1111/vde.12468.

28. Plant JD, Neradelik MB, Polissar NL, et al. Agreement between allergenspecific IgE assays and ensuing immunotherapy recommendations from four commercial laboratories in the USA. Vet Dermatol 2014;25:15-e6.

41. Simpson AC, Schissler JR, Rosychuk RAW. The frequency of urinary tract infection and subclinical bacteriuria in dogs with allergic dermatitis treated with oclacitinib: a prospective study. Vet Dermatol 2017;28:485-e113.

29. Ihrke PJ, Norton AL, Ling GV, et al. Urinary tract infection associated with long-term corticosteroid administration in dogs with chronic skin diseases. JAVMA 1985;186:43-46.

42. Nuttall T, Reece D, Roberts E. Life-long diseases need life-long treatment: long-term safety of ciclosporin in canine atopic dermatitis.

Vet Rec 2014;174:3-12.

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PEER REVIEWED 43. Dip R, Carmichael J, Letellier I, et al. Concurrent short-term use of prednisolone with cyclosporine A accelerates pruritus reduction and improvement in clinical scoring in dogs with atopic dermatitis. BMC Vet Res. 2013;9:173.

48. Kovalik M, Taszkun I, Pomorski Z, et al. Evaluation of a human generic formulation of ciclosporin in the treatment of canine atopic dermatitis with in vitro assessment of the functional capacity of phagocytic cells.

Vet Rec 2011;168:537-542.

44. Panteri A, Strehlau G, Helbig R, et al. Repeated oral dose tolerance in dogs treated concomitantly with ciclosporin and oclacitinib for three weeks. Vet Dermatol 2016;27:22-e7.

49. Navarro C, Crastes N, Benizeau E, et al. Voluntary acceptance and consumption of two oral ciclosporin formulations in dogs: two randomised, controlled studies. Ir Vet J 2015;68:3.

45. McAtee BB, Cummings KJ, Cook AK, et al. Opportunistic invasive cutaneous fungal infections associated with administration of cyclosporine to dogs with immune-mediated disease. J Vet Intern Med 2017 Sep 9.

50. Archer TM, Boothe DM, Langston VC, et al. Oral cyclosporine treatment in dogs: a review of the literature. J Vet Intern Med 2014;28:1-20.

46. Peterson AL, Torres SM, Rendahl A, et al. Frequency of urinary tract infection in dogs with inflammatory skin disorders treated with ciclosporin alone or in combination with glucocorticoid therapy: a retrospective study. Vet Dermatol 2012;23:201-e43.

51. Michels GM, Ramsey DS, Walsh KF, et al. A blinded, randomized, placebo-controlled, dose determination trial of lokivetmab (ZTS00103289), a caninized, anti-canine IL-31 monoclonal antibody in client owned dogs with atopic dermatitis. Vet Dermatol 2016;27:478-e129.

47. Steffan J, Strehlau G, Maurer M, et al. Cyclosporine A pharmacokinetics and efficacy in the treatment of atopic dermatitis in dogs. J Vet Pharmacol Ther 2004;27:231-238.

CONTINUING EDUCATION

Canine Atopic Dermatitis: Updates on Diagnosis and Treatment LEARNING OBJECTIVES

After reading this article, practitioners should be able to determine which flare factors (or environmental conditions) are responsible for canine atopic dermatitis (CAD), a common chronic relapsing pruritic skin disease of dogs. The readers will recognize the importance of a rational diagnostic and multimodal therapeutic plan that provides the best management of this disease. Atopic dogs need to be evaluated regularly, and treatment plans should be modified for each patient, particularly with every flare of clinical signs.

TOPIC OVERVIEW

CAD is a chronic, incurable, but manageable inflammatory and pruritic disease of the skin. Medications used to treat allergic skin disease mask clinical signs but do not change the disease process unless allergen-specific immunotherapy is implemented.

1. Oclacitinib is a novel a. Monoclonal antibody b. JAK inhibitor c. Glucocorticoid d. Calcineurin inhibitor 2. Which of the following lesions and sites would be likely to be present in dog affected by flea allergy dermatitis? a. Lichenification and scaling in the ventral neck b. Recurrent otitis externa c. Self-induced alopecia lumbosacral area, tail base, and caudomedial thighs d. Erythematous papules in the interdigital areas

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CE: CANINE ATOPIC DERMATITIS

The article you have read has been submitted for RACE approval for 1 hour of continuing education credit and will be opened for enrollment when approval has been received. To receive credit, take the approved test online for free at vetfolio.com/journal-ce.

Free registration on VetFolio.com is required. Questions and answers online may differ from those below. Tests are valid for 2 years from the date of approval.

3. Reactive treatment in atopic dermatitis means: a. Treatment is applied continuously with daily frequency b. Treatment is applied intermittently c. Treatment is applied twice weekly only on weekends (Saturday, Sunday) d. Treatment is applied only when clinical signs develop

NOTE Questions online may differ from those here; answers are available once CE test is taken at vetfolio.com/journal-ce. Tests are valid for 2 years from date of approval.

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CONTINUING EDUCATION

4. A 2-year-old castrated male dog, Leo, presents with nonseasonal signs of erythema, lichenification, and self-induced alopecia around the eyes, lips, concave pinnae, ventral neck, axillae, groin, and elbow folds. You suspect the patient may have CAD. For immediate treatment of acute flare of CAD, you would recommend: a. Oclacitinib b. Cyclosporine c. Cetirizine d. Essential fatty acids 5. Which one of the following interventions (treatment or test) should be your next step for Leo? a. Skin scrapes for Sarcoptes or Demodex species b. Dietary restriction-provocation test (food trial) c. Allergy serum test d. Treatment with essential fatty acids 6. Which diet would be the most suitable for a diet trial in a dog with a beef allergy? a. Hydrolyzed beef diet b. Store-brand chicken-based diet c. Kangaroo-based novel protein diet d. None of the above 7. Which one of the following lesions and sites would be least likely to be present in a dog affected by classical CAD? a. Lichenification in the groin b. Self-induced alopecia on the dorsal thorax c. Recurrent otitis externa d. Erythematous macules, patches, and papules in the axillae

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8. Which of the following medications is the most appropriate for a 2-week treatment of acute CAD flare? a. Diphenhydramine b. Prednisolone c. Cyclosporine d. Essential fatty acids

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9. Lokivetmab is a caninized monoclonal antibody against which cytokine? a. Interleukin-2 b. Interleukin-31 c. Interleukin-33 d. Interleukin-5

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10. Proactive therapy is treatment that involves: a. Low-dose, q12h continuous application of anti-inflammatory therapy to previously affected skin b. Application of anti-inflammatory therapy applied only when skin lesions develop c. Low-dose, intermittent application of antiinflammatory therapy to previously affected skin d. Low-dose application of anti-inflammatory therapy applied only when skin lesions develop

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FLUID THERAPY: PART 1

Fluid Therapy in Hospitalized Patients: Patient Assessment and Fluid Choices Bridget M. Lyons, VMD Lori S. Waddell, DVM, DACVECC University of Pennsylvania

Fluid therapy is an essential component of the treatment plan in many hospitalized small animal patients. Choice of fluid type and dose depends on available resources as well as the patient’s interstitial hydration status, hemodynamic stability, and electrolyte balance.

This article reviews fluid distribution, hydration assessment, types of body fluid losses, types of fluids available, and calculation of fluid needs. A second article will focus on calculating free water deficit, monitoring fluid therapy, when to discontinue fluids, and the approach to fluid therapy in patients with electrolyte abnormalities and specific fluid balance states.

how water is distributed in the body and thus how fluid therapy affects overall hydration.

DISTRIBUTION OF BODY WATER

Separating the intracellular and extracellular compartments are cell membranes, through which water can move freely by osmosis.1 The intravascular space is partitioned off from other compartments by the vascular endothelium. Within the capillaries is the endothelial glycocalyx, a web of membranebound glycoproteins and proteoglycans that plays an important role in fluid dynamics.2

Total body water (TBW) is commonly described in terms of individual fluid compartments.

Although fluid balance in the body is a dynamic process—water is constantly being lost through elimination and metabolic processes and gained from food and water intake—it is useful to use compartments to understand

TBW makes up approximately 60% of total body weight in adults (FIGURE 1) and 80% in pediatric animals.1 This percentage is lower in overweight patients because fat contains less water than other body tissues.1 Intracellular fluid accounts for two-thirds of TBW.1 Of the remaining third, approximately 75% is in the interstitial space and 25% is in the intravascular space1; a small amount is contained in the transcellular space (eg, cerebrospinal fluid, synovial fluid).

GO WITH THE FLOW Fluid therapy is a mainstay of care in the hospitalized small animal patient. Assessment of a patient’s fluid deficits and ongoing needs will help determine what variety of fluid and rate to use.

shutterstock.com/NEstudio

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PEER REVIEWED

The classic Starling model of fluid dynamics did not take into account the endothelial glycocalyx, and it was previously thought that fluid was filtered at the arteriolar end of the capillary and subsequently resorbed on the venule side, with the rate of filtration and absorption related to both the hydrostatic pressure and the colloid oncotic pressure (COP) in the capillary and the interstitial space.2 Newer research has shown that the COP of the subglycocalyx space replaces interstitial COP and that fluids are not absorbed on the venule side but rather are returned to the circulation via the lymphatic system.2,4

TYPES OF FLUID LOSSES Fluid loss in small animals can be isotonic, hypotonic, or hypertonic. While osmolality is a measure of all solutes in solution, tonicity refers only to the effective solutes in solution; that is, those that cannot cross a membrane and so exert an osmotic pressure.

Isotonic losses, such as those observed with vomiting and diarrhea, occur when the fluid being lost has an osmolality similar to that of plasma. With isotonic fluid loss, sodium concentrations are typically normal; however, if the animal is able to drink water, hyponatremia may result from replacement with a hypotonic fluid.

Hypotonic losses occur when the type of fluid being lost has a higher concentration of water than plasma, such as with diabetes insipidus and panting. The loss of a hypotonic fluid, or water in excess of sodium, can result in hypernatremia. Although isotonic replacement fluids may benefit some patients with hypotonic losses, others benefit from fluids that contain more free water.

Hypertonic losses, or loss of sodium in excess of water, are uncommon but can be seen with hypoadrenocorticism, third-space loss of fluid (such as pleural or peritoneal effusion), and diuretic administration.1 Excess loss of hypertonic fluid can result in hyponatremia.

Treatment of hypernatremia and hyponatremia will be discussed in Fluid Therapy: Part 2.

DETERMINING FLUID DEFICITS Assessment of Hydration Dehydration refers to lack of fluid in the interstitial compartment, whereas hypovolemia describes lack of fluid in the intravascular compartment.

Intracellular dehydration cannot be detected on physical examination and is primarily assessed via changes in sodium concentration.

Although dehydrated patients have some hypovolemia, clinical changes do not occur until dehydration exceeds 10%.1 The minimum percentage dehydration that can be detected on physical examination is 5%, and dehydration greater than 12% is likely to be fatal.1 Percentage dehydration can be estimated by examining mucous membrane moisture, skin turgor (FIGURE 2), eye position (FIGURE 3), and corneal moisture, as described in TABLE 1.1 Overhydration of the interstitial compartment, which occurs in cases of fluid overload, can also be detected on physical examination. Signs of overhydration include chemosis, serous nasal discharge, increased skin turgor, peripheral edema, ascites, pleural effusion, and pulmonary edema.

Intravascular fluid 1/4 of ECF Interstitial fluid 3/4 of ECF

ECF 1/3

Intracellular fluid 2/3

FIGURE 1. Distribution of body water within the various compartments. ECF, extracellular fluid.

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FLUID THERAPY

FIGURE 2. Checking skin turgor on a dehydrated cat. Note the degree to which the skin can be tented away from the catâ&#x20AC;&#x2122;s body.

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Hydration status should be interpreted with the clinical status of the patient in mind. For example, hypersalivation in a nauseated patient may result in moist mucous membranes, but the patient may still have decreased skin turgor, indicating dehydration.

Conversely, decreased skin turgor may be present in emaciated or older animals regardless of hydration status.

In pediatric animals, skin turgor is often maintained because of increased skin elasticity, making this finding more difficult to interpret in this population.

The 4 primary means of fluid delivery are intravenous (IV), intraosseous, subcutaneous (SC), and enteral. IV fluid administration is generally preferred for hospitalized patients because the delivery rate can be controlled and changed quickly depending on patient requirements.

Assessment of Intravascular Volume Intravascular volume can also be assessed on physical examination. Signs of decreased intravascular volume, or hypovolemia, include increased heart rate, fair or weak pulses, coolness of the distal limbs, weakness, and pale mucous membranes. Although blood pressure can initially be normal or even high in the early stages of hypovolemic shock, a normal blood pressure in conjunction with physical examination findings consistent with hypovolemia should

not dissuade clinicians from considering hypovolemia and treating appropriately because compensated shock will eventually progress to the uncompensated stage.

METHOD OF DELIVERY The 4 primary means of fluid delivery are intravenous (IV), intraosseous, subcutaneous (SC), and enteral. IV fluid administration is generally preferred for hospitalized patients because the delivery rate can be controlled and changed quickly depending on patient requirements.

Intraosseous catheters can be placed in neonates, exotic patients, and other small animals in which IV access cannot be obtained, but these catheters may not be tolerated for extended periods once patients have been resuscitated.

SC fluids are not recommended for hospitalized patients because they are more difficult to titrate. In addition, patients with intravascular deficits require more aggressive support; SC fluids are not adequately absorbed because of peripheral vasoconstriction and so are not indicated for treating shock. Patients that are easily overloaded may receive too much fluid with no means of discontinuation once fluids are administered, resulting in fluid overload.

In patients that are being discharged from the hospital, SC fluids may become a component of home care if they are well tolerated and there are ongoing excessive fluid losses.

Enteral fluids are ideal in patients that can tolerate them because enteral delivery is the most physiologic method to provide water. Many hospitalized patients cannot take in adequate water for various reasons (eg, vomiting, nausea, hypotension). If a patient can tolerate TABLE 1 Subjective Estimation of Percentage Dehydration Based on Physical Examination Parameters5

FIGURE 3. Dehydrated cat on IV fluids. Note the sunken eyes.

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FLUID THERAPY

ESTIMATED DEHYDRATION

PHYSICAL EXAMINATION FINDINGS

<5%

Not detectable

5%–6%

Tacky mucous membranes

6%–8%

Decreased skin turgor Dry mucous membranes

8%–10%

Retracted globes within orbits

10%–12%

Persistent skin tent Dull corneas Evidence of hypovolemia

>12%

Hypovolemic shock Death

Data adapted from reference 5.

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Important Safety Information for IVERHART MAX Chewable Tablets: For use in dogs only. All dogs should be tested for heartworm infection before starting a preventive program. Use with caution in sick, debilitated, or underweight animals and dogs weighing less than 10 lbs. The safe use of this drug has not been evaluated in pregnant or lactating bitches. Adverse reactions following the use of ivermectin include: Depression/lethargy, vomiting, anorexia, diarrhea, mydriasis, ataxia, staggering, convulsions, and hypersalivation. For complete product information refer to the product insert. To obtain a package insert, contact Veterinary Technical Product Support at 1-800-338-3659, or visit us.virbac.com. *Based on an average SKU price for HEARTGARD Plus Chewables of $4.59 and IVERHART MAX Chewable Tablets of $3.73. Prices as of May 2017 and subject to change at any time.

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PEER REVIEWED

enteral water but is not willing to drink an adequate amount, a feeding tube can be used to provide fluids. An esophagostomy tube placed for feeding can also be used for water intake. Alternatively, a nasoesophageal tube can be placed to provide water and liquid diets (FIGURE 4).

This is particularly useful in patients that cannot tolerate IV fluids, such as those with cardiac and/or renal disease.

TYPES OF FLUIDS Crystalloids Crystalloids are fluids containing small solutes (<500 Da), most of which are electrolytes, in particular sodium and chloride.3 The electrolytes and water in these solutions move easily across the endothelium into the interstitial space. More than 60% to 80% of a crystalloid solution distributes out of the intravascular space within 20 to 30 minutes.3,4 Crystalloid solutions can be classified as isotonic, hypotonic, or hypertonic.

Isotonic Isotonic crystalloids have an osmolarity and sodium concentration similar to those of plasma. They are commonly used to treat interstitial dehydration and hypovolemia because fluid losses are typically isotonic or hypotonic.

FIGURE 4. A mixed-breed dog with neurologic disease and a nasoesophageal tube placed to administer water.

The dog was unable to drink on its own and had developed hypernatremia. The tube allows administration of free water to correct the hypernatremia.

Isotonic solutions are considered balanced (or buffered) if their electrolyte composition and pH closely mirror those of plasma. Common balanced isotonic crystalloids include Plasmalyte-A (baxter.com), Normosol-R (hospira.com), and lactated Ringerâ&#x20AC;&#x2122;s solution (LRS) (TABLE 2). Metabolism of these

TABLE 2 Comparison of Various Crystalloid Solutions7 OSMOLARITY, MOSM/L

SODIUM, MEQ/L

CHLORIDE, MEQ/L

POTASSIUM, MEQ/L

MAGNESIUM, MEQ/L

BUFFER (MEQ/L)

Plasmalyte-A

295

140

98

5

3

Acetate (27) Gluconate (23)

Plasmalyte-56 and 5% dextrose

362

40

40

13

3

Acetate (16)

Normosol-R

295

140

98

5

3

Acetate (27) Gluconate (23)

Normosol-M and 5% dextrose

363

40

40

13

3

Acetate

LRS

273

130

109

4

0

Lactate (28)

D5W

253

0

0

0

0

0

0.45% NaCl

154

77

77

0

0

0

0.9% NaCl

310

154

154

0

0

0

3% NaCl

1026

513

513

0

0

0

7.5% NaCl

2566

1283

1283

0

0

0

CRYSTALLOID

66

FLUID THERAPY

FEATURES

buffers consumes hydrogen ions, resulting in an alkalinizing effect. The lactate in LRS is metabolized by the liver; thus, it is a suboptimal choice for patients with hepatic dysfunction or diabetic ketoacidosis because they will not be able to convert lactate to bicarbonate. Neonates are able to use lactate as a fuel source, making LRS the preferred fluid choice for young patients.

CAUTION: Federal (US) law restricts this drug to use by or on the order of a licensed veterinarian.

BRIEF SUMMARY: Please consult package insert for complete product information.

Many available crystalloids are buffered solutions meant for fluid replacement (eg, Plasmalyte-A, Normosol-R). For longer-term treatment of patients receiving IV fluids, maintenance fluids (eg, Plasmalyte-56, Normosol-M) are solutions that contain lower sodium and higher potassium concentrations to meet maintenance needs. These solutions use dextrose to increase the osmolality of what would otherwise be a hyposmolar fluid. In practice, replacement fluids are frequently used as maintenance fluids and are often well tolerated in patients that do not have underlying conditions, such as cardiac or renal disease, that make them unable to handle the excess sodium.

Indications: For use in dogs to prevent canine heartworm disease by eliminating the tissue stage of heartworm larvae (Dirofilaria immitis) for a month (30 days) after infection and for the treatment and control of roundworms (Toxocara canis, Toxascaris leonina), hookworms (Ancylostoma caninum, Uncinaria stenocephala, Ancylostoma braziliense), and tapeworms (Dipylidium caninum, Taenia pisiformis).

In contrast, 0.9% saline is an unbuffered isotonic crystalloid. Although the tonicity of 0.9% saline is similar to that of plasma, the pH is relatively low (5.5) and the solution contains no electrolytes other than sodium and chloride. Isotonic saline is the fluid of choice for treating hypochloremic metabolic alkalosis because the acid–base disturbance cannot be resolved without correction of chloride. It also promotes calciuresis and so can be used in the treatment of hypercalcemia.

PRECAUTIONS: Use with caution in sick, debilitated, or underweight animals and dogs weighing less than 10 lbs (see Animal Safety). The safe use of this drug has not been evaluated in pregnant or lactating bitches.

WARNINGS: For use in dogs only. Keep this and all drugs out of reach of children. In safety studies, testicular hypoplasia was observed in some dogs receiving 3 and 5 times the maximum recommended dose monthly for 6 months (see Animal Safety). In case of ingestion by humans, clients should be advised to contact a physician immediately.

Physicians may contact a Poison Control Center for advice concerning cases of ingestion by humans.

All dogs should be tested for existing heartworm infection before starting treatment with IVERHART MAX Chewable Tablets, which are not effective against adult D. immitis.

Infected dogs should be treated to remove adult heartworms and microfilariae before initiating a heartworm prevention program.

While some microfilariae may be killed by the ivermectin in IVERHART MAX Chewable Tablets at the recommended dose level, IVERHART MAX Chewable Tablets are not effective for microfilariae clearance. A mild hypersensitivity-type reaction, presumably due to dead or dying microfilariae and particularly involving a transient diarrhea, has been observed in clinical trials with ivermectin alone after treatment of some dogs that have circulating microfilariae.

Hypotonic Hypotonic crystalloids are useful for treating patients with hypotonic fluid losses that result in hypernatremia or patients that have renal disease and cannot excrete the salt load of balanced isotonic solutions. Two commonly used hypotonic solutions are 0.45% saline and 5% dextrose in water (D5W).

The former has an osmolarity of 154 mOsm/L, approximately half the normal plasma osmolarity in dogs and cats. D5W has a high osmolarity at 250 mOsm/L, but the dextrose in solution is rapidly metabolized upon infusion, resulting in infusion of what is essentially free water.

ADVERSE REACTIONS: In clinical field trials with ivermectin/ pyrantel pamoate, vomiting or diarrhea within 24 hours of dosing was rarely observed (1.1% of administered doses).

The following adverse reactions have been reported following the use of ivermectin: depression/lethargy, vomiting, anorexia, diarrhea, mydriasis, ataxia, staggering, convulsions and hypersalivation.

ANIMAL SAFETY: Studies with ivermectin indicate that certain dogs of the Collie breed are more sensitive to the effects of ivermectin administered at elevated dose levels (more than 16 times the target use level of 6 mcg/kg) than dogs of other breeds. At elevated doses, sensitive dogs showed adverse reactions which included mydriasis, depression, ataxia, tremors, drooling, paresis, recumbency, excitability, stupor, coma and death. No signs of toxicity were seen at 10 times the recommended dose (27.2 mcg/lb) in sensitive Collies. Results of these studies and bioequivalence studies support the safety of ivermectin products in dogs, including Collies, when used as recommended by the label.

Hypertonic Hypertonic saline is the primary hypertonic fluid administered in small animal medicine. Hypertonic saline from 3-7.5% is primarily used during resuscitation in hypovolemic shock and to decrease intracranial pressure.

Administration of hypertonic saline results in free water shifting from the interstitial space into the intravascular space, expanding the extracellular volume by approximately 3 times the volume administered.3,6 Movement of fluid into the intravascular space results in interstitial and intracellular dehydration, so a hypertonic saline bolus should be followed by a bolus of isotonic crystalloid, although this is not necessary if used to treat cerebral edema.

In a laboratory safety study, 12-week-old Beagle puppies receiving 3 and 5 times the recommended dose once weekly for 13 weeks demonstrated a dose-related decrease in testicular maturation compared to untreated controls.

HOW SUPPLIED: IVERHART MAX Chewable Tablets are available in four dosage strengths for dogs of different weights. Each strength comes in a box of 6 chewable tablets, packed 10 boxes per display box.

STORAGE INFORMATION: Store at 20°C -25°C (68°F-77°F), excursions permitted between 15°C-30°C (59°F-86°F).

Protect product from light.

The intravascular expansion is short lived, lasting approximately 30 minutes before redistribution.3 Because the effect is transient, hypertonic saline can be combined with colloid solutions to prolong time present in the intravascular space.

For technical assistance or to report adverse drug reactions, please call 1-800-338-3659.

Manufactured by: Virbac AH, Inc. Fort Worth, TX 76137 NADA 141-257, Approved by FDA

In addition to intravascular expansion, hypertonic saline increases cardiac output and tissue perfusion through a weak positive inotropic effect, reduction of endothelial swelling, and arteriolar vasodilation.3 JANUARY/FEBRUARY 2018

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Colloids Colloid solutions contain large molecules (>10,000 Da) and tend to remain in the intravascular space longer than crystalloids.3,4 The most commonly used colloid solutions in veterinary medicine contain hydroxyethyl starch (HES).8 HES solutions are thought to be most effective in treating hypovolemia because the colloid should theoretically remain in the intravascular space, although some extravasation does occur. The half-life of various colloids depends on their molecular properties. As mentioned above, the lack of absorption at the venules means that administration of a colloid does not necessarily “pull” interstitial water into the intravascular space but opposes filtration out of the intravascular space.2

Signs of overhydration include chemosis, serous nasal discharge, increased skin turgor, peripheral edema, ascites, pleural effusion, and pulmonary edema.

The use of HES has been under debate—the risk for acute kidney injury (AKI) and increased mortality in humans has resulted in a “black box” warning from the Food and Drug Administration.8,9 A retrospective study evaluating the occurrence of AKI and death in dogs receiving HES showed an increased risk for both; however, this study evaluated a 10% HES solution, which is thought to be associated with increased risk for AKI compared with 6% solutions.10 Other potential adverse effects of HES include coagulopathy, pruritus, reticuloendothelial dysfunction, proinflammatory effects, volume overload, hepatopathy, and anaphylaxis.2,4 The incidence of AKI and increased mortality in humans has been associated with longer infusion times and higher volumes than are used in most veterinary patients,4 and further research is needed in animal patient populations to determine the risk-to-benefit ratio. HES is still used in our institution, although with somewhat more caution than previously.

Other colloids include fresh or fresh frozen plasma, canine albumin, and human serum albumin. Plasma provides albumin and coagulation factors. Because the concentration of albumin

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FLUID THERAPY

present is similar to that in plasma, large volumes must be administered to have an oncotic effect.

Approximately 40 to 50 mL/kg must be administered to raise the serum albumin by 1 g/dL.1,4 Although the administration of an albumin solution would be preferable, species-specific albumin is expensive and is only intermittently available.1,4 Concentrated human serum albumin can be administered to dogs for the treatment of hypoalbuminemia, but because it is not completely homologous with canine albumin, there is potential for an immediate or delayed hypersensitivity reaction, which can result in death.1,4 Immediate hypersensitivity reactions are more common in healthy patients.

Although immediate hypersensitivity reactions are rare in critically ill patients that receive human serum albumin, delayed hypersensitivity is observed as a serious complication in this population.

DETERMINING A FLUID RATE When deciding if fluid therapy is appropriate for a patient, a few basic questions should be asked before determining a fluid therapy plan (BOX 1). These questions can be answered based on assessment of the patient for hypovolemia and dehydration (see Determining Fluid Deficits). Once the patient’s volume status and hydration needs have been determined, a fluid therapy plan can be developed.

Fluid Therapy for Shock Patients The goal of fluid therapy in patients with hypovolemic and distributive shock is to rapidly restore effective circulating volume and improve

BOX 1 Questions to Ask When Formulating a Fluid Plan 

Is the patient hypovolemic? Does it need a bolus?



Is the patient dehydrated?



What type of fluid should be given?



What route?



How much fluid should be given, and over what time period?



When can the fluids be discontinued?

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cellular oxygenation. Cardiogenic shock should be ruled out before the administration of crystalloid and colloid fluids because of the risk for exacerbation of pulmonary vasculature fluid overload.

The “shock bolus” of fluids is based on the estimated blood volume of the patient: 60 to 90 mL/kg in dogs and 40 to 60 mL/kg in cats. This amount of fluid is typically not administered because most patients have not lost their entire blood volume and respond to lower volumes of fluids. In dogs, recommendations are to start by administering 10-20ml/kg boluses of isotonic crystalloids over 15 to 30 minutes and reassessing the patient’s intravascular volume status after each bolus.

Subsequent boluses can be administered according to whether perfusion parameters (eg, heart rate, blood pressure, capillary refill time, mucous membrane color) are improved. Cats are typically less tolerant of fluid boluses than dogs, so slightly lower volumes (10 to 15 mL/kg) are recommended. If a synthetic colloid is used, 5 mL/kg in dogs and 3 mL/kg in cats should be administered over 15 to 30 minutes.

Daily Fluid Therapy

■■ Dehydration

■■ Ongoing

Ongoing losses include excessive urine output in polyuric animals, vomiting, diarrhea, blood loss, and third spacing. These losses vary by patient and may be difficult to calculate. A general rule is to estimate the amount of ongoing loss in a patient in mL/h and then reassess the patient in 4 to 6 hours to determine whether this amount needs to be adjusted.

As an example, the daily fluid needs of a 5-kg patient that is estimated to be 6% dehydrated (to be corrected over 24 hours) and has estimated ongoing losses of 1 mL/kg per hour can be calculated as follows: deficit: 5 kg × 0.06 = 0.3 L × 1000 = 300 mL to be corrected over 24 hours (300 mL/24 h) = 12.5 mL/h

■■ Dehydration

■■ Ongoing

rate: 2 mL/kg/h × 5 kg = 10 mL/h

losses: 1 mL/kg/h × 5 kg = 5 mL/h

■■ Total

rate (dehydration + maintenance + losses): 12.5 + 10 + 5 = 27.5 mL/h

SUMMARY Fluid therapy is a mainstay of care in the hospitalized small animal patient. Assessment of a patient’s fluid deficits and ongoing needs will help determine what variety of fluid and rate to use.

needs

losses

The volume of crystalloid needed to correct dehydration can be calculated using the following formula: Body weight (kg) × [% dehydration/100] = fluid deficit (L) Dehydration can be corrected over 24 to 48 hours.

Once the deficit has been determined, the total volume can be divided by the number of hours over which the dehydration is to be corrected to obtain a mL/h rate.

Maintenance fluid needs are based on both sensible and insensible losses. These can be estimated as 40-60 ml/kg per day or 2-3 ml/kg per hour in adults (pediatric patients require slightly higher rates).

70

Body weight (kg)0.75 × 70 = RER ≈ daily fluid requirement

■■ Maintenance

In stable dehydrated patients, the goal of fluid therapy is to replace interstitial losses while simultaneously taking into account the patient’s baseline fluid requirements and any excessive losses. Thus, daily crystalloid fluid needs are calculated on the basis of 3 values: ■■ Maintenance

Because of alterations in lean body mass, these estimates may not be as accurate for animals that weigh <2 or >40 kg.1 Because daily water requirements parallel resting energy requirements (RERs), the formula to determine RER can be used:

FLUID THERAPY

References 1. Rudloff E. Assessment of hydration. In: Silverstein D, Hopper K, eds.

Small Animal Critical Care Medicine. 2nd ed. St. Louis. MO: Elsevier; 2015:302-311.

2. Woodcock TE, Woodcock TM. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesthes 2012;108(3):384-394.

3. Liu DT, Silverstein DC. Crystalloids, colloids, and hemoglobin-based oxygen carrying solutions. In: Silverstein D, Hopper L, eds. Small Animal Critical Care Medicine. 2nd ed. St. Louis, MO: Elsevier; 2015:311315.

4. Cazolli D, Prittie J. The crystalloid-colloid debate: consequences of resuscitation fluid selection in veterinary critical care. J Vet Emerg Crit Care 2015;25(1):6-19.

5. Muir WW, DiBartola SP. Fluid therapy. In: Kirk RW, ed. Current Veterinary Therapy VIII. Philadelphia: WB Saunders; 1983:33.

6. Silverstein DC, Aldrich J, Haskins SC, et al. Assessment of changes in blood volume in response to resuscitative fluid administration in dogs. J Vet Emerg Crit Care 2005;15(3):185-192.

FEATURES

Bridget M. Lyons Bridget M. Lyons, VMD, is a resident in emergency and critical care at the University of Pennsylvania. She graduated from the University of Pennsylvania School of Veterinary Medicine and completed a small animal rotating internship at the Animal Medical Center. Her research interests include sepsis and the role of the microbiome in critical illness.

Lori S. Waddell Lori S. Waddell, DVM, DACVECC, is clinical professor of critical care medicine at the University of Pennsylvania, working in the intensive care unit. She graduated from Cornell University’s College of Veterinary Medicine and completed an internship at Angell Memorial Animal Hospital in Boston, Massachusetts. After her internship, she briefly worked as an emergency clinician in private practice before completing a residency in emergency and critical care at the University of Pennsylvania’s Veterinary Hospital.

Her current areas of interest include fluid therapy, acid– base disturbances, and coagulation in critically ill patients.

7. Mathews KA. The various types of parenteral fluids and their indications. Vet Clin N Am 1998;28(3):483-513.

8. Glover PA, Rudloff E, Kirby R. Hydroxyethyl starch: a review of pharmacokinetics, pharmacodynamics, current products, and potential clinical risks, benefits, and use. J Vet Emerg Crit Care 2014;24(6):642-661.

9. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev 2013;2:1-64.

10. Hayes G, Benedecenti L, Mathews K. Retrospective cohort study on the incidence of acute kidney injury and death following hydroxyethyl starch (HES 10% 250/0.5/5:1) administration in dogs (2007-2010). J Vet Emerg Crit Care 2016;26(1):35-40.

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Clinical Insights

FOCUS ON INFECTIOUS DISEASE Leptospirosis

74

IMAGING ESSENTIALS Ultrasonography of the Gastrointestinal Tract: Stomach, Duodenum, and Jejunum

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FOCUS ON

Leptospirosis Madeline Fujishiro, DVM Kate E. Creevy, DVM, MS, DACVIM Texas A&M University

A 1-year-old, castrated male miniature dachshund was presented for an acute onset of lethargy, anorexia, and vomiting.

HISTORY The patient was evaluated upon referral for a 48-hour history of lethargy, anorexia, and vomiting.

He was also noticeably polyuric and polydipsic during the 48 hours prior to presentation.

He was reported to be housed predominantly indoors and lived with one other dog, a Yorkshire terrier, who was unaffected. He had no history of prior illness and had received his complete series of puppy core vaccinations (distemper virus, parvovirus, adenovirus, and parainfluenza series; and rabies initial vaccine).

He had not yet received his first adult boosters.

Physical Examination and Diagnostics On original presentation to the referring veterinarian, the patient was depressed, weighed 3.0 kg, was assessed to be 5% to 7% dehydrated, and was febrile (102.8°F).

A complete blood count (CBC) and serum biochemical profile were performed (TABLE 1). His urine specific gravity (USG) before fluid therapy was 1.012.

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FOCUS ON LEPTOSPIROSIS

Initial Therapy The patient was administered 50% dextrose and NutriCal (vetoquinolusa.com) orally. He was hospitalized for 8 hours and received IV fluid therapy, maropitant, famotidine, and ampicillin. He was sent home with sucralfate, famotidine, and instructions to feed a bland diet. When his lethargy and anorexia continued into the following day, referral was recommended.

PHYSICAL EXAMINATION AND INITIAL DIAGNOSTICS On presentation, the patient was quiet and alert, adequately hydrated, weighed 3.18 kg, and was in adequate body condition (BCS 5/9). His rectal temperature was elevated (102.7°F). He appeared painful on palpation of his abdomen, and his kidneys were subjectively enlarged. The remainder of his physical examination revealed no abnormalities.

A CBC, serum biochemical profile, and urinalysis were performed (TABLE 2).

DIFFERENTIAL DIAGNOSIS Based on the patient’s signalment, history, physical examination, and initial blood work results, the

CLINICAL INSIGHTS

TABLE 1 Pertinent Referring Veterinarian Blood Work Results VALUE

RESULT

REFERENCE RANGE

27 (H)

4.0−15.5

Neutrophils (10 cells/mcL)

22.1 (H)

2.06−10.6

Monocytes (10 cells/mcL)

1.62 (H)

0−0.84

35 (L)

36−60

169 (L)

170−400

249 (H)

5−131

52 (H)

6−31

382 (H)

92−324

COMPLETE BLOOD COUNT White blood cells (103 cells/mcL) 3

3

Hematocrit (%) Platelet count (10 cells/mcL) 3

SERUM BIOCHEMICAL PROFILE Alkaline phosphatase (U/L) Blood urea nitrogen (mg/dL) Cholesterol (mg/dL) Creatinine (mg/dL) Phosphorus (mg/dL)

1

0.5−1.6

10.5 (H)

2.5−6.0

1.012 (L)

1.015−1.045

URINALYSIS Specific gravity H, high; L low.

TABLE 2 Pertinent Clinicopathologic Abnormalities VALUE

RESULT

REFERENCE RANGE

COMPLETE BLOOD COUNT White blood cells (103 cells/mcL)

36.7 (H)

6.0−17.0

Neutrophils (103 cells/mcL)

28.26 (H)

3.0−11.5

Monocytes (103 cells/mcL)

5.87 (H)

0.15−1.25

35 (L)

36−60

clumped

200−500

473 (H)

24−147

Hematocrit (%) Platelet count (10 cells/mcL) 3

SERUM BIOCHEMICAL PROFILE Alkaline phosphatase (U/L) Blood urea nitrogen (mg/dL)

69 (H)

5−29

Cholesterol (mg/dL)

394 (H)

120−247

Creatinine (mg/dL)

2.09 (H)

0.3−2.0

8.3 (H)

2.9−6.2

Specific gravity

1.012 (L)

1.015−1.045

Protein (mg/dL)

100 (H)

negative−trace

Phosphorus (mg/dL) URINALYSIS

H, high; L low.

primary differentials for renal azotemia with concurrent inflammatory leukogram included: ■■ Leptospirosis ■■ Toxin

exposure, including ethylene glycol

■■ Bacterial

pyelonephritis

■■ Septicemia

ADDITIONAL DIAGNOSTICS AND DIAGNOSIS Abdominal radiographs revealed bilateral renomegaly and mild hepatomegaly.

Abdominal ultrasound confirmed the presence of renomegaly with bilateral pyelectasia (FIGURE 1).

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TABLE 3 Microscopic Agglutination Test Titers SEROVAR

TITER

Pomona

1:400

Icterohaemorrhagiae

Negative

Canicola

1:200

Grippotyphosa

1:1600

Hardjo

FIGURE 1. This ultrasound image depicts a subjectively enlarged right kidney, measuring 4.9 cm in length. There is mild pyelectasia, the cortex is mildy hyperechoic, and the corticomedillary junction is slightly indistinct.

Negative

Bratislava

1:200

Autumnalis

1:200

Sejroe

Negative

Antibiotics

Scant peritoneal and retroperitoneal effusion was also present.

Aerobic culture of urine was reported as “no growth” after 3 days of incubation.

Blood and urine samples were submitted for leptospirosis polymerase chain reaction (PCR) testing and microscopic agglutination test (MAT) titers. PCR results were negative in blood and positive in urine for leptospirosis. MAT titers were strongly supportive of natural leptospirosis infection (TABLE 3).

IV ampicillin and sulbactam was initiated due to the high suspicion for leptospirosis. The patient improved clinically with these therapies within a few days. Once leptospirosis MAT titers and PCR results were received, he was transitioned to oral doxycline.

Patient Monitoring The patient was hospitalized for 8 days. Serial biochemical profiles supported a positive response to therapy (TABLE 4).

THERAPY FOR LEPTOSPIROSIS

FOLLOW-UP

Supportive Care

A week after discharge from the hospital, blood work performed by the referring veterinarian revealed no abnormalities, and creatinine had remained within the normal reference range (1.4 mg/dL). Convalescent

The patient was treated supportively with IV fluid therapy, maropitant, famotidine, and buprenorphine.

TABLE 4 Serial Biochemical Profile Abnormalities RESULT REFERENCE RANGE

VALUE

DAY OF HOSPITALIZATION 1

3

4

5

6

7

8

9

24−147

473

323

392

308

374

468

463

504

5−29

69

40

68

67

34

31

23

43

Cholesterol (mg/dL)

120−247

394

353

358

316

292

*

*

*

Creatinine (mg/dL)

0.3−2.0

2.09

1.3

2.87

2.94

1.56

1.26

1.14

1.4

Phosphorus (mg/dL)

2.9−6.2

8.3

5.9

7.6

6.7

5.7

*

*

*

Alkaline phosphatase (U/L) Blood urea nitrogen (mg/dL)

*Value not measured

76

FOCUS ON LEPTOSPIROSIS

CLINICAL INSIGHTS

MAT titers performed by the same laboratory revealed a 4-fold decrease in the serovar Grippotyphosa (1:400), further supporting the diagnosis of leptospirosis.

DISCUSSION: OVERVIEW OF LEPTOSPIROSIS Pathogenesis Leptospirosis is a bacterial disease with a worldwide distribution and is of importance in human and veterinary medicine due to its zoonotic potential.1,2 Naming conventions for leptospiral pathogens are unusual, as the organisms are commonly described by serovar names, rather than species names. There are hundreds of known serovars of the genus Leptospira, and disease in dogs is caused by the pathogenic serovars of the species Leptospira interrogans and Leptospira kirschneri.2,3 Different serovars are adapted to various reservoir hosts, including the raccoon (FIGURE 2), opossum, vole, and rat; the dog is likely the reservoir host for serovar Canicola.1–3 These hosts excrete the organisms in their urine.

Incidental hosts, such as humans and dogs, are infected when their intact mucous membranes or abraded skin comes into direct or indirect contact with infected urine.1,2 Leptospires prefer a warm and wet environment, therefore, disease is found more predominantly in warmer climates with higher annual rainfall.1,2 The incubation period ranges from a few days to a week and varies based on infecting dose, strain, and immune response of the host.1

illness depending on infecting strain, geographical location, and immune response of the host.1,2 Common clinical presentations include lethargy, anorexia, vomiting, abdominal pain, or changes in urination (polyuria, oliguria, or anuria).2,4 Leptospirosis should be suspected in dogs with evidence of febrile renal or hepatic disease, vasculitis, uveitis, or pulmonary hemorrhage (TABLE 5).1,2 Most consistent hematologic findings include leukocytosis, anemia, and thrombocytopenia. Biochemical abnormalities reflect renal damage and reduced glomerular filtration rate (azotemia, hyperphosphatemia) and/or hepatic injury (hyperbilirubinemia, elevated liver enzyme activity).2,4 Bleeding tendencies are likely multifactorial in origin, reflecting both vascular and hepatic injury.

Although attempts have been made, no consistent correlation between infecting serovar and clinical presentation has been identified.1 This is likely at least partly attributable to the inability of antibody tests to predict the infecting serovar.1,5

Definitive Diagnosis There is no single “gold standard” test for an antemortem diagnosis of canine leptospirosis. The diagnosis is based on the combination of clinical TABLE 5 Common Clinical Syndromes and Manifestations Associated With Leptospirosis CLINICAL SYNDROME

Clinical Findings Disease may manifest as peracute disease or subclinical infection, with the severity of clinical

CLINICAL MANIFESTATIONS Polyuria, oliguria, or anuria Polydipsia

Renal failure

Abdominal pain Dehydration Azotemia Hyperphosphatemia Icterus Cranial organomegaly

Hepatic injury

Coagulopathy Hyperbilirubinemia Elevated liver enzyme activity Peripheral edema Pleural effusion Peritoneal effusion Petechiation

Vasculitis

Epistaxis Uveitis

FIGURE 2. The raccoon is an important reservoir host for leptospirosis.

Pulmonary hemorrhage syndrome (appears to be more prevalent in European cases)

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signs, clinicopathologic abnormalities, and methods of organism detection, including MAT titers, acute and convalescent titers, PCR, culture, histopathology, and IDEXX SNAP Lepto Test (idexx.com).

MAT titers. MAT is an antibody test that assesses the ability of serial dilutions of patient serum to cause agglutination of live leptospires via dark field microscopy.2 The reported titer is the highest patient serum dilution causing 50% agglutination of leptospires in the reaction.1 There is no consensus on the cutoff value for a negative titer.

Natural infection should be strongly suspected with a single MAT titer of 1:800 or greater with consistent clinical signs and clinicopathologic abnormalities without leptospiral vaccination within the past 4 months.2,3 MAT titers cannot be used to predict the infecting serovar due to cross-reactivity among different serogroups from shared leptospiral antigens.1,5 Acute and convalescent titers. Dogs frequently have negative MAT results in the acute phase of infection.1 If there is a high index of suspicion for disease, and the initial titer does not support infection, convalescent titers in 2 to 4 weeks should be performed. A 4-fold change (increase or decrease) in a titer supports recent infection with leptospirosis.1â&#x20AC;&#x201C;3

PCR testing. PCR can be used to detect pathogenic leptospiral nucleic acids. During the first 10 days of infection, organism numbers are highest in blood. Afterwards, they are found in the highest concentration in urine.1 Because timing of infection is not often known, pairing blood and urine PCR testing may increase diagnostic sensitivity.

False-negative results may occur with recent antimicrobial treatment or when the number of sampled organisms is low.1 Recent vaccination does not interfere with PCR assays.2 PCR testing should be paired with other diagnostic methods like MAT titers.1 Culture. Leptospires can be cultured on special media; however, the diagnostic utility is limited because the organism is both fragile under transport conditions and slow growing (up to a 3- to 6-month incubation period).1,2 Histopathology. Organisms may be visualized with silver stains, immunohistochemistry, or fluorescence in situ hybridization on biopsied kidney tissue.6 SNAP Lepto Test. This point-of-care test detects antibodies to Leptospira species by enzyme-linked immunosorbent assay (ELISA) and reports a qualitative positive or negative result. Independent studies of its utility in field conditions have not yet been reported.

Therapeutic Approach Madeline Fujishiro Madeline Fujishiro, DVM, is a small animal internal medicine resident at Texas A&M University College of Veterinary Medicine and Biomedical Sciences. She received her DVM from Colorado State University, followed by a 1-year small animal rotating internship at University of Georgia, before starting her residency at Texas A&M University.

Kate E. Creevy Kate E. Creevy, DVM, MS, DACVIM, received her DVM from the University of Tennessee and completed a small animal rotating internship at the University of Minnesota before entering emergency practice for 4 years. She joined the University of Georgia (UGA) faculty as a clinical instructor in emergency medicine, subsequently completing both her masterâ&#x20AC;&#x2122;s degree in infectious disease and her residency in small animal internal medicine at that institution. She remained on the faculty at UGA through early 2016 and has recently joined the faculty at Texas A&M University, where she is an associate professor of small animal internal medicine.

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FOCUS ON LEPTOSPIROSIS

Appropriate supportive therapy should be provided to each patient based on the clinical manifestation of disease.

IV fluid therapy must be initiated for the treatment of acute kidney injury associated with leptospirosis and to correct for dehydration. Urine output should be monitored and fluids adjusted accordingly once hydration is restored. Ideally, these patients should be hospitalized at 24-hour care facilities, and referral for dialysis should be offered for patients in oliguric or anuric renal failure.7 Acute kidney injury in dogs has been comprehensively and practically reviewed elsewhere.8 The current recommendation for treatment of leptospirosis is doxycycline 5 mg/kg PO q12h for 2 weeks. In clinically ill patients that cannot tolerate doxycycline, IV ampicillin can be administered to eliminate the leptospiremic phase. Once tolerated, a 2-week course of doxycycline is required to eliminate the organism from the renal tubules.1,2

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Prognosis With early and aggressive treatment that includes attentive monitoring, prognosis for recovery is excellent.

Urine output should be monitored; development of oliguric renal failure significantly worsens the prognosis and prompts escalation of therapy.8 Resolution of azotemia occurs within 10 to 14 days, however, damaged renal tissue may continue to regenerate for more than than 4 weeks after treatment.

Some dogs may suffer from permenent renal damage.1,6 Hyperbilirubinemia, if present, may be slower to resolve.

Prevention Vaccination In the United States, vaccines for prevention of leptospirosis contain the serovars Icterohaemorrhagiae and Canicola and may include Grippotyphosa and Pomona.

Vaccines effectively prevent disease after challenge with serovars included in the vaccine, and disease is rare in dogs vaccinated with the four-serovar vaccine; however, cross-protection of vaccines against other pathogenic serovars requires further investigation.1,3,6 Vaccines have been shown to provide immunity from serovar-specific challenge for 1 year, but longer duration of

BOX 1 Precautions for Leptospirosis Patients

80



lace a warning sign on cage designating animal as P leptospirosis patient (suspected or diagnosed)



void patient contact with pregnant or immunocompromised A humans



House patient away from high-traffic areas



Minimize patient movement around hospital



Disinfect urine spills promptly



Wash hands before and after handling patient



Wear personal protective equipment, including gloves, disposable gown, protective eyewear, and facemask when handling patient



Place an indwelling urinary catheter, if necessary, to monitor urine output or control incontinence



alk uncatheterized dogs outside frequently to urinate in a W restricted area that is easily decontaminated

FOCUS ON LEPTOSPIROSIS

immunity has not been demonstrated. While previously associated with a type I hypersensitivity reaction, the vaccine is no longer considered more reactive than other vaccines.6 Vaccination is recommended annually in “at-risk” dogs.9 At-risk dogs include those with exposure to wildlife reservoirs and/or contaminated water sources.1 Exposure Avoidance Additional disease prevention includes avoidance of environmental water sources and contact with wildlife. Wildlife reservoirs of leptospirosis, such as rats and raccoons, are present in urban and suburban environments. As evidenced by this case, even small-breed dogs traditionally thought to have a low risk of exposure can contract the disease.

Public Heath Similar to dogs, humans can become infected with leptospires from contaminated water sources or contact with reservoir hosts. Reports of transmission of disease from incidental hosts to other animals (eg, dogs to humans) are rare; however, in-hospital precautions should be taken to minimize the risk of zoonotic transmission (BOX 1).6 All dogs presenting with acute renal failure should be handled as having leptospirosis until proven otherwise.

At home, owners should avoid contact with their dog’s urine, wearing gloves to clean up spilled urine until antimicrobial therapy is complete.1 References 1. Sykes JE, Hartmann K, Lunn KF, et al. 2010 ACVIM small animal consensus statement on leptospirosis: diagnosis, epidemiology, treatment, and prevention. J Vet Intern Med 2011;25(1):1-13.

2. Lunn KF. Leptospirosis. In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy XV. St. Louis, MO: Elsevier; 2014:1286-1289.

3. Green CE, Sykes JE, Moore GE, et al. Leptospirosis. In: Green CE, ed.

Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, MO: Elsevier; 2012:431-447.

4. Goldstein RE, Lin RC, Langston CE, et al. Influence of infecting serogroup on clinical features of leptospirosis in dogs. J Vet Intern Med 2006;20:489-494.

5. Harkin KR, Hays MP. Variable-number tandem-repeat analysis of leptospiral DNA isolated from canine urine samples molecularly confirmed to contain pathogenic leptospires. JAVMA 2016;249(4):399-405.

6. Sykes JE. Leptospirosis. In: Sykes JE, ed. Canine and Feline Infectious Diseases. St. Louis, MO: Elsevier; 2014:474-485.

7. van de Maele I, Claus A, Haesebrouck F, et al. Leptospirosis in dogs: a review with emphasis on clinical aspects. Vet Rec 2008;163(14):409-413.

8. Ross L. Acute kidney injury in dogs and cats. Vet Clin North Am Small Anim Pract 2011;41(1):1-14.

9. Klaasen HL, Molkenboer MJ, Vrijenhoek MP, et al. Duration of immunity in dogs vaccinated against leptospirosis with a bivalent inactivated vaccine. Vet Microbiol 2003;95(1-2):121-132.

Make killing fleas & ticks

Preferred by dogs1 and dog owners2 – NexGard® (afoxolaner) makes it easy to protect your canine patients against fleas and four of the most common species of ticks in North America.

Data on file at Merial.

Data on file at Merial. Based on veterinary dispensed dose data.

1 2

NexGard is a Merial product.

Merial is now part of Boehringer Ingelheim.

NexGard® is a registered trademark, and FRONTLINE VET LABSTM is a trademark, of Merial. ©2017 Merial, Inc., Duluth, GA. All rights reserved. NEX18TRADEAD1 (01/18).

IMPORTANT SAFETY INFORMATION: NexGard® (afoxolaner) is for use in dogs only. The most frequently reported adverse reactions included pruritus, vomiting, dry/flaky skin, diarrhea, lethargy, and lack of appetite. The safe use of NexGard in pregnant, breeding, or lactating dogs has not been evaluated. Use with caution in dogs with a history of seizures. For more information, see full prescribing information or visit www.NexGardForDogs.com.

PEER REVIEWED

IMAGING ESSENTIALS

Ultrasonography of the Gastrointestinal Tract: Stomach, Duodenum, and Jejunum Elizabeth Huynh, DVM, and Clifford R. Berry, DVM, DACVR University of Florida

LOCALIZATION AND SCANNING TECHNIQUE Typically, an 8 to 10-MHz curved array or 12-MHz linear transducer is used for dogs and cats.

Animals are usually scanned in dorsal recumbency; however, right and left lateral recumbency may assist with displacement of gas and fluid in the stomach to better visualize deeper structures.

Longitudinal axis and transverse axis views of the different segments of the gastrointestinal tract are necessary for a complete examination.

Maintain a consistent sequence when evaluating the complete gastrointestinal tract; preferably, in the following order: all parts of the stomach (fundus, body, pyloric antrum), pyloroduodenal junction (pyloric sphincter), duodenum, jejunum, ileum, ileocecocolic (cat) or ileocolic (dog) junction, cecum, and parts of the colon (ascending, transverse, descending).

Stomach The stomach is scanned initially in long axis plane, relative to the patient, which creates a transverse view of the stomach, beginning at the fundic portion located immediately caudal to the left division of the liver. The fundus is located in the left craniolateral quadrant,

82

IMAGING ESSENTIALS

the body of the stomach is located closer to midline as the transducer is swept to the right of the patient, and the pyloric antrum can extend to the right side of the patient depending on the degree of distension.

The pylorus and pyloroduodenal junction is found closer to midline in most cats. In deep chested dogs, a right dorsal intercostal approach may be needed to better visualize the pyloroduodenal junction. Occasionally, the gastroesophageal junction (cardia) may be visualized.

Duodenum After imaging the pyloroduodenal junction, the orad portion of the descending duodenum is visualized.

The descending duodenum is followed caudally, keeping it in long axis, along the right lateral abdominal body wall in the dog. An intercostal approach may be needed to identify the cranial aspect of the descending duodenum in the dog.

When the patient is placed in dorsal recumbency, the right kidney may be used to identify the duodenum as it will be located ventral or ventrolateral to that kidney within the near field of the image.

The descending duodenum in the cat will be either in a midline position or just to the right of midline.

ADVERTORIAL

THE LONE STAR TICK IS SPREADING: KNOW WHAT TO LOOK FOR Part one of a three-part series The Lone Star tick is an aggressive, biting parasite that feeds on numerous hosts, including deer, dogs and humans. Already common in the southern United States, the Lone Star tick continues to expand to new parts of the country.1 It’s important to know how to help your clients protect their pets.

SOLVING A MEDICAL MYSTERY Recent coverage of the Lone Star tick in popular media has focused on the spread of an unusual red meat allergy known as alpha-gal

How can you tell?

syndrome. Those with the condition discover they suddenly cannot tolerate red meat despite having eaten it normally their whole lives.

Symptoms of a severe allergic reaction often develop three to six hours after meat consumption with patients often waking in the middle of the night with post-dinner hives and anaphylaxis.2 Dr. Scott Commins, an allergist at the University of North CarolinaChapel Hill, was part of the team that confirmed a link between the Lone Star tick’s bite and the mysterious allergy. He and his colleagues

Scutum

“To identify any tick, look at the scutum!

The scutum’s markings are unique to each species. Even when a tick is fully engorged, you can still see the scutum.”

-Dr. Thomas Mather, professor of entomology and Director of the TickEncounter Resource Center at the University of Rhode Island

found that maps depicting cases of Rocky Mountain spotted fever – also transmitted by the Lone Star tick – neatly matched maps of reported alpha-gal syndrome cases.3

Match the Tick!

A GROWING POPULATION The Centers for Disease Control and Prevention report the Lone Star tick can already be found in at least 30 U.S. states.4 However, sightings are popping up in new areas all the time. Tick experts including Dr. Thomas Mather, professor of entomology and director of the TickEncounter Resource Center at the University of Rhode Island, attribute their spread to an abundance of hosts in the form of a growing white-tailed deer population in different areas of the country. 5 A TICK IS A TICK IS A TICK? Think a tick is a tick, no matter what kind? Not true. Identifying the species can help in understanding the risk for tick-borne diseases when advising clients, says Dr. Brian Herrin, veterinary parasitologist transmit Lyme disease, but it does pose a risk by transmitting other pathogens, such as those that cause Rocky Mountain spotted fever and ehrlichiosis in dogs.6 Do you know what to look for? Test your skills with our quiz to the right. You can also learn more about the Lone Star tick and tickborne diseases at the TickEncounter Resource Center website: tickencounter.org.

A. Brown Dog Tick; B. American Dog Tick; C. Lone Star Tick; D. Black Legged (Deer )Tick

at Kansas State University. For example, the Lone Star tick does not

1 Springer YP, Jarnevich CS, Barnett DT, et al. Modeling the Present and Future Geographic Distribution of the Lone Star Tick, Amblyomma americanum (Ixodida: Ixodidae), in the Continental United States. Am J Trop Med Hyg. 2015; 93(4): 875-890. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596614/. Accessed October 11, 2017.

2 Wolver SE, Sun DR, Commins SP, et al. A peculiar cause of anaphylaxis: no more steak? The journey to discovery of a newly recognized allergy to galactose-alpha-1-3-galactose found in mammalian meat. J Gen Intern Med. 2013; 28(2): 325. https://www.ncbi.nlm.nih.gov/pubmed/22815061. Accessed October 11, 2017.

3 Commins SP, James HR, Kelly EA, et al. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose. J Allergy Clin Immunol. 2011;127(5):1286-1293. https://www.ncbi.nlm. nih.gov/pmc/articles/PMC3085643/. Accessed October 11, 2017.

4 “Approximate distribution of the Lone Star tick.” Centers for Disease Control and Prevention. https://www.cdc.gov/ ticks/maps/lone_star_tick.html. Accessed October 10, 2017.

5 Paddock CD, Yabsley MJ. Ecological havoc, the rise of white-tailed deer, and the emergence of Amblyomma americanum-associated zoonosis in the United States. Curr Top Microbiol Immunol. 2007; 315:289-324. https://www.ncbi.nlm. nih.gov/pubmed/17848069. Accessed October 11, 2017.

6 “Amblyomma americanum (Lone Star ticks).” University of Rhode Island TickEncounter Center. http://tickencounter. org/tick_identification/lone_star_tick#top. Accessed October 10, 2017. © 2018 Merial Inc., Duluth, GA. All rights reserved. NEXLSTADVERTORIAL1

PEER REVIEWED

Jejunum The jejunum is evaluated in its entirety by sweeping the transducer back and forth (side to side) across the abdomen in an overlapping pattern, beginning cranially and slowly progressing caudally.

It may not be possible to trace the jejunum continuously from orad to aborad due to gas interposition or shadowing artifacts from intestinal contents.

NORMAL ULTRASONOGRAPHIC FEATURES OF THE GASTROINTESTINAL TRACT Before imaging the gastrointestinal tract, the patient should be fasted, however, this may not be feasible in all circumstances. Ideally, fasting will prevent ultrasound artifacts, such as reverberation artifact and beam attenuation,1 from impeding the structures either adjacent and dorsal to the gastrointestinal tract or the far wall of the gastrointestinal tract that is being imaged.

The layering of the walls of the gastrointestinal tract can be assessed using ultrasonography and has a characteristic pattern of alternating hyperand hypoechoic layers (FIGURE 3); the luminalmucosal interface, submucosal, and serosal layers are hyperechoic; and the mucosal and muscularis layers are hypoechoic. An easy mnemonic is M&Mâ&#x20AC;&#x2122;s (mucosa and muscularis) are chocolate (dark/hypoechoic).

The gastrointestinal tract layering is as follows from the lumen, centrally, to the serosal margin, peripherally: 1. Interface between lumen and mucosa (hyperechoic) 2. Mucosa (hypoechoic) 3. Submucosa (hyperechoic) 4. Muscularis (hypoechoic) 5. Serosa (hyperechoic)

Reverberation artifact appears as multiple, equidistantly spaced linear reflections (FIGURE 1). This artifact occurs when multiple echoes are erroneously processed due to a delayed return of the signal.1 Beam attenuation appears as a reduction of the ultrasound signal at depth in the far field (FIGURE 2).

This is due to the attenuation of the ultrasound beam in the near field secondary to gastrointesinal contents.1

FIGURE 1. Longitudinal axis of a cat stomach filled with gas.

Notice the dirty shadowing created by the gas reverberation artifact deep to the superficial stomach wall.

84

IMAGING ESSENTIALS

FIGURE 2. Longitudinal axis of the stomach in a cat. Note the hyperechoic line on the luminal side of the stomach. The material in the stomach hyperattenuates the ultrasound waves so that it is totally black in the deep portion of the image.

FIGURE 3. Longitudinal axis view of a segment of jejunum of a normal dog demarcating the different layers of the small intestines.

CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Description: NexGard® (afoxolaner) is available in four sizes of beef-flavored, soft chewables for oral administration to dogs and puppies according to their weight. Each chewable is formulated to provide a minimum afoxolaner dosage of 1.14 mg/lb (2.5 mg/ kg). Afoxolaner has the chemical composition 1-Naphthalenecarboxamide, 4-[5- [3-chloro-5-(trifluoromethyl)-phenyl]-4, 5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl.

Indications: NexGard kills adult fleas and is indicated for the treatment and prevention of flea infestations (Ctenocephalides felis), and the treatment and control of Black-legged tick (Ixodes scapularis), American Dog tick (Dermacentor variabilis), Lone Star tick (Amblyomma americanum), and Brown dog tick (Rhipicephalus sanguineus) infestations in dogs and puppies 8 weeks of age and older, weighing 4 pounds of body weight or greater, for one month.

Dosage and Administration: NexGard is given orally once a month, at the minimum dosage of 1.14 mg/lb (2.5 mg/kg).

Dosing Schedule: Body Weight 4.0 to 10.0 lbs.

10.1 to 24.0 lbs.

24.1 to 60.0 lbs.

60.1 to 121.0 lbs.

Over 121.0 lbs.

Afoxolaner Per Chewables Chewable (mg) Administered 11.3 One 28.3 One 68 One 136 One Administer the appropriate combination of chewables

NexGard can be administered with or without food. Care should be taken that the dog consumes the complete dose, and treated animals should be observed for a few minutes to ensure that part of the dose is not lost or refused. If it is suspected that any of the dose has been lost or if vomiting occurs within two hours of administration, redose with another full dose. If a dose is missed, administer NexGard and resume a monthly dosing schedule.

Flea Treatment and Prevention: Treatment with NexGard may begin at any time of the year. In areas where fleas are common year-round, monthly treatment with NexGard should continue the entire year without interruption.

To minimize the likelihood of flea reinfestation, it is important to treat all animals within a household with an approved flea control product.

Tick Treatment and Control: Treatment with NexGard may begin at any time of the year (see Effectiveness).

Contraindications: There are no known contraindications for the use of NexGard.

Warnings: Not for use in humans. Keep this and all drugs out of the reach of children. In case of accidental ingestion, contact a physician immediately.

Precautions: The safe use of NexGard in breeding, pregnant or lactating dogs has not been evaluated. Use with caution in dogs with a history of seizures (see Adverse Reactions).

Adverse Reactions: In a well-controlled US field study, which included a total of 333 households and 615 treated dogs (415 administered afoxolaner; 200 administered active control), no serious adverse reactions were observed with NexGard.

Over the 90-day study period, all observations of potential adverse reactions were recorded. The most frequent reactions reported at an incidence of > 1% within any of the three months of observations are presented in the following table. The most frequently reported adverse reaction was vomiting. The occurrence of vomiting was generally self-limiting and of short duration and tended to decrease with subsequent doses in both groups. Five treated dogs experienced anorexia during the study, and two of those dogs experienced anorexia with the first dose but not subsequent doses.

Table 1: Dogs With Adverse Reactions.

Treatment Group Afoxolaner

Vomiting (with and without blood) Dry/Flaky Skin Diarrhea (with and without blood) Lethargy Anorexia

N1 17 13 13 7 5

% (n=415) 4.1 3.1 3.1 1.7 1.2

Oral active control

N2 25 2 7 4 9

% (n=200) 12.5 1.0 3.5 2.0 4.5

Number of dogs in the afoxolaner treatment group with the identified abnormality.

Number of dogs in the control group with the identified abnormality.

In the US field study, one dog with a history of seizures experienced a seizure on the same day after receiving the first dose and on the same day after receiving the second dose of NexGard. This dog experienced a third seizure one week after receiving the third dose. The dog remained enrolled and completed the study. Another dog with a history of seizures had a seizure 19 days after the third dose of NexGard. The dog remained enrolled and completed the study. A third dog with a history of seizures received NexGard and experienced no seizures throughout the study.

To report suspected adverse events, for technical assistance or to obtain a copy of the MSDS, contact Merial at 1-888-6374251 or www.merial.com/NexGard. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth.

Mode of Action: Afoxolaner is a member of the isoxazoline family, shown to bind at a binding site to inhibit insect and acarine ligand-gated chloride channels, in particular those gated by the neurotransmitter gamma-aminobutyric acid (GABA), thereby blocking preand post-synaptic transfer of chloride ions across cell membranes. Prolonged afoxolaner-induced hyperexcitation results in uncontrolled activity of the central nervous system and death of insects and acarines. The selective toxicity of afoxolaner between insects and acarines and mammals may be inferred by the differential sensitivity of the insects and acarines’ GABA receptors versus mammalian GABA receptors.

Effectiveness: In a well-controlled laboratory study, NexGard began to kill fleas four hours after initial administration and demonstrated >99% effectiveness at eight hours. In a separate well-controlled laboratory study, NexGard demonstrated 100% effectiveness against adult fleas 24 hours post-infestation for 35 days, and was ≥ 93% effective at 12 hours post-infestation through Day 21, and on Day 35. On Day 28, NexGard was 81.1% effective 12 hours post-infestation. Dogs in both the treated and control groups that were infested with fleas on Day -1 generated flea eggs at 12- and 24-hours post-treatment (0-11 eggs and 1-17 eggs in the NexGard treated dogs, and 4-90 eggs and 0-118 eggs in the control dogs, at 12- and 24-hours, respectively). At subsequent evaluations post-infestation, fleas from dogs in the treated group were essentially unable to produce any eggs (0-1 eggs) while fleas from dogs in the control group continued to produce eggs (1-141 eggs).

In a 90-day US field study conducted in households with existing flea infestations of varying severity, the effectiveness of NexGard against fleas on the Day 30, 60 and 90 visits compared with baseline was 98.0%, 99.7%, and 99.9%, respectively.

Collectively, the data from the three studies (two laboratory and one field) demonstrate that NexGard kills fleas before they can lay eggs, thus preventing subsequent flea infestations after the start of treatment of existing flea infestations.

In well-controlled laboratory studies, NexGard demonstrated >97% effectiveness against Dermacentor variabilis, >94% effectiveness against Ixodes scapularis, and >93% effectiveness against Rhipicephalus sanguineus, 48 hours post-infestation for 30 days. At 72 hours post-infestation, NexGard demonstrated >97% effectiveness against Amblyomma americanum for 30 days.

Animal Safety: In a margin of safety study, NexGard was administered orally to 8 to 9-week-old Beagle puppies at 1, 3, and 5 times the maximum exposure dose (6.3 mg/kg) for three treatments every 28 days, followed by three treatments every 14 days, for a total of six treatments. Dogs in the control group were sham-dosed. There were no clinically-relevant effects related to treatment on physical examination, body weight, food consumption, clinical pathology (hematology, clinical chemistries, or coagulation tests), gross pathology, histopathology or organ weights. Vomiting occurred throughout the study, with a similar incidence in the treated and control groups, including one dog in the 5x group that vomited four hours after treatment.

In a well-controlled field study, NexGard was used concomitantly with other medications, such as vaccines, anthelmintics, antibiotics (including topicals), steroids, NSAIDS, anesthetics, and antihistamines. No adverse reactions were observed from the concomitant use of NexGard with other medications.

Storage Information: Store at or below 30°C (86°F) with excursions permitted up to 40°C (104°F).

How Supplied: NexGard is available in four sizes of beef-flavored soft chewables: 11.3, 28.3, 68 or 136 mg afoxolaner. Each chewable size is available in color-coded packages of 1, 3 or 6 beef-flavored chewables.

1 2

NADA 141-406, Approved by FDA Marketed by: Frontline Vet Labs™, a Division of Merial, Inc. Duluth, GA 30096-4640 USA Made in Brazil. ®NexGard is a registered trademark, and TMFRONTLINE VET LABS is a trademark, of Merial. ©2015 Merial. All rights reserved.

1050-4493-03 Rev. 1/2015

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PEER REVIEWED

Canine and feline gastrointestinal wall thicknesses vary depending on the segment assessed (TABLE 1).

if ingesta, gas, and/or fluid are present within the lumen of the stomach (FIGURE 4).

Stomach

The pyloric sphincter can be recognized due to its hyperechoic mucosa in contrast to the pyloric antral mucosa and duodenal mucosa, which are hypoechoic.

The normal canine and feline stomach is located caudal to the liver. The different portions of the stomach include the cardia, fundus, body, and pyloric antrum, leading into the pyloroduodenal junction (pyloric sphincter).

In most cases, the cardia is not identified due to its cranial location and interposition of the liver, although, occasionally, it can be identified through dorsal intercostal acoustic windows.

The transverse section of the empty feline stomach has a characteristic wagon wheel appearance, often with a thick, hyperechoic submucosal layer due to fat deposition (FIGURE 5).

Duodenum and Jejunum The duodenum in the dog is the thickest segment of the small intestinal tract and contains the thickest

The fundus, located in the left cranial abdominal cavity, is scanned in longitudinal and transverse axes. Next, the transducer is moved medially towards midline to scan the body of the stomach.

In the feline patient, the body of the stomach can be found on the left of midline; the canine gastric body can be located right of midline

BOX 1 Criteria for assessing the small intestines include: 

Uniformity in diameter



Wall thickness (TABLE 1)



Discrete wall layering



Presence of luminal contents



Peristalsis

FIGURE 4. Longitudinal axis view of the stomach of a normal dog with a gas filled stomach. Note the hyperechoic gas interface (white arrow) with distal reverberation artifact and dirty shadowing; the lack of rugal folds within the gastric lumen is due to distension of the lumen with gas.

TABLE 1 Normal Ultrasonographic Measurements (95% Confidence Intervals) of Gastrointestinal Tract Wall Thickness in Dogs and Cats SEGMENT OF GASTROINTESTINAL TRACT

DOG WALL THICKNESS

CAT WALL THICKNESS

3 − 5 mm2

2 mm (inter-rugal)3,4 and 4 mm (rugal fold thickness)3

Up to 5 mm5

2 − 2.5 mm 6,7

Jejunum

2 − 5 mm 6

2 − 2.5 mm 6,7

Ileum

2 − 4 mm 6

2.5 − 3.2 mm4,6,7

Colon

2 − 3 mm 6

1.4 − 2.5 mm 6

Cecum

1.5 mm 8

1.5 − 2 mm 8-10

Stomach Duodenum

Note: Normal ultrasonographic measurements of the individual layers of the canine11 and feline7,12 gastrointestinal tract have been described in recent literature.

86

IMAGING ESSENTIALS

CLINICAL INSIGHTS

mucosal layer, representing 63% of the total wall thickness. At times, Peyer’s patches, or pseudoulcers, can be seen when using ultrasonography, forming focal depressions of the mucosal surface (FIGURE 6).

The feline duodenum has a similar thickness and appearance to the jejunum; the mucosa is not as apparent as in the dog (FIGURE 7).

Within the cranial aspect of the descending duodenum, the major duodenal papilla can be seen (FIGURE 8), particularly when using a high resolution, high frequency, linear or curved array transducer. The major duodenal papilla in the cat varies from 2.9 to 5.5 mm in width and has a maximum thickness of 4 mm on the transverse view.13

In normal dogs and cats, the small intestines are relatively uniform in distribution. Depending on the segment of small intestine, some layers may be thicker than others.

This can be used to identify the different segments of intestines. For example, in the dog, the mucosal layer of the duodenum is thicker than the mucosal layer of the jejunum.

A

B

FIGURE 5. The transverse axis view of an empty stomach of a normal cat has the appearance of a wagon wheel. Note the thick, hyperechoic submucosal layer of the stomach, commonly due to fat deposition (white arrowhead).

FIGURE 6. Longitudinal axis view of the proximal descending duodenum of a normal dog. The focal indentation (white arrow) in the duodenal mucosa (rectangular or square hyperechoic area) is a “pseudoulcer” due to a Peyer’s patch; this is a normal finding in the dog.

FIGURE 7. Longitudinal axis view of the proximal descending duodenum of a normal cat (A) and normal dog (B). The cat has a thinner mucosal layer and thicker submucosal layer than the dog.

FIGURE 8. Longitudinal axis view of the proximal descending duodenum of a normal dog. The major duodenal papilla (calipers) is located along the dorsal margin of the duodenum.

JANUARY/FEBRUARY 2018

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TVPJOURNAL.COM

87

PEER REVIEWED

STOMACH ABNORMALITIES

Gastric Foreign Bodies

Dilation

Gastric foreign bodies are often diagnosed on survey radiographs and can sometimes be diagnosed using ultrasound, depending on the contents in the gastric lumen. Often, foreign material has a hyperechoic interface with intense distal acoustic shadowing. If the foreign body is surrounded by fluid, it can be readily seen (FIGURE 10). The shape and size of the foreign material varies.

If the stomach becomes progressively distended or dilated, the stomach wall will become thinner, the wall layering will be difficult to distinguish, and the rugal folds will be less distinct.

Depending upon its composition, gastric content may be hypoechoic to hyperechoic.

A gas dilated stomach may contain reverberation artifact within the far field of the image, resulting in the inability to visualize abnormalities of the dorsal aspect of the gastric wall or lumen.

Pyloric Outflow Obstruction Causes of pyloric outflow obstruction include pyloric stenosis, foreign bodies, inflammatory disease, and neoplasia.

Congenital hypertrophic pyloric stenosis causes circumferential thickening of the pylorus and is more common in dogs than cats. Ultrasonographically, gastric wall thickness > 6 to 7 mm and muscular layer thickness > 4 mm is considered pathologic (FIGURE 9).2 Foreign bodies lodged in the pyloric region typically have an irregular or geometric shape and strong acoustic shadowing.

Chronic hypertrophic pyloric gastropathy also causes muscular or mucosal hypertrophy; pyloric wall thicknesses for affected dogs ranges from 9 to 15.3 mm, and the thickness of the muscular layer ranges from 3 to 5.4 mm.9

FIGURE 9. Longitudinal axis view of the stomach of a dog diagnosed with gastric outflow obstruction. Note the abnormally thickened, hyperechoic muscularis layer of the stomach, measuring up to 1 cm in thickness (calipers).

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IMAGING ESSENTIALS

Gastric Wall Thickening Non-neoplastic lesions, such as gastritis, can produce a diffuse, mild to moderate thickening with preservation of the wall layering (FIGURE 10).

Neoplastic lesions usually cause focal loss of wall layering along with varying degrees of wall thickening (FIGURE 11).8,14,15

Malignant Gastric Neoplasms Adenocarcinoma is the most common gastric neoplasm in the dog. This neoplasm is extremely rare in the cat.

Most carcinomas are located in the lesser curvature and pylorus in the dog.

Features of gastric adenocarcinoma include a pseudolayered pattern, asymmetrical transmural thickening, and altered wall layering with a poorly echogenic lining to the mucosal and/or serosal wall layers.16-18

FIGURE 10. Transverse axis view of the stomach of a dog with a gastric linear foreign body. Note the hyperechoic foreign material (black arrowhead) with distal acoustic shadowing (ď&#x192;?) and gastric wall thickening (calipers measuring 9 mm thick), presumptively secondary to gastritis.

CLINICAL INSIGHTS

A pseudo-layered pattern has been described in some canine gastric epithelial neoplasia, such as carcinoma.17 In that study, pseudo-layering was characterized by transmural thickening with altered wall layering, as well as a poorly echogenic lining along the innermost and/or outermost portions of the gastric wall, separated by a more echogenic central region.17 Leiomyosarcomas produce focal masses, often involving the gastric antrum, and thickening of the muscular layer of the gastric wall.19 These neoplasms are usually small, rounded masses that protrude into the gastric lumen at the level of the cardia. The luminal surface of these lesions is usually smooth, due to their origin in the muscularis layer.

Lymphoma is the most common gastric neoplasm in the cat. It appears as a focal mass, multiple masses, or diffuse infiltrative neoplasia, characterized by thickening and/or loss of normal layered appearance to the wall (FIGURE 11).20-22 Features of malignant histiocytosis include a single, well circumscribed, hypoechoic mass with well-defined borders and an abnormal loss of wall layering in the dog.23

A

Benign Gastric Neoplasms Adenomas can occur in dogs and cat and can appear flat or polypoid.18 Gastric leiomyomas are the second most common neoplasm in the stomach of a dog. They form single or multiple, sessile, round polyps protruding into the lumen.24 The most common locations include the gastric cardia or gastroesophageal junction.25 Leiomyomas cannot be differentiated from leiomyosarcomas using ultrasonography alone; cytology or histopathology are required for definitive diagnosis.

Other Causes of Gastric Wall Masses or Abnormal Wall Layering Chronic hypertrophic gastritis can cause severe gastric wall thickening without a loss of wall layering, or a thickened, hypoechoic layer can be seen surrounding the pyloric lumen (interpreted as a thickened muscularis layer, histologically).9 In particular, the rugal folds of the mucosal layer become severely thickened and project into the lumen.26,27 Eosinophilic sclerosing fibroplasia occurs in cats. Ultrasonographically, they are focal mass lesions or mural thickening at the pyloric antrum with a loss of wall layering (FIGURE 12).28,29 Pythiosis is a chronic, pyogranulomatous infection caused by the water mold Pythium insidiosum. This can cause focal thickening of the gastric wall, with partial or complete obliteration of the wall layers (FIGURE 13).30,31

B

FIGURE 11. Longitudinal axis view of the stomach of a cat diagnosed with gastrointestinal lymphoma via cytology (A).

Note the loss of wall layering and the severely thickened and hypoechoic gastric wall (calipers). Blood flow through this hypoechoic mass is confirmed using color Doppler (B).

FIGURE 12. Longitudinal axis view of a segment of jejunum of a cat diagnosed with eosinophilic sclerosing fibroplasia via cytology. Note the abnormally thickened, hypoechoic muscularis layer, causing overall thickening of this segment (calipers). This disease is difficult to distinguish between other inflammatory and neoplastic diseases but can be confirmed using cytologic or histopathologic methods.

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The site of a gastropexy may have a focal thickening and alteration of normal wall layers.6,32

gastric wall and a hyperechoic line in the mucosal or submucosal layer, representing mineralization.33,34

Uremic gastritis can be seen in patients with chronic uremia. Findings include thickening of the

Nonspecific gastritis, such as infectious or toxic (eg, peroxide toxicity), can cause wall edema and wall thickening without a total loss of wall layering.

Absence of visible abnormalities on ultrasound does not rule out gastritis. Occasionally, perigastric hyperechoic fat is noted in association with gastritis.

DUODENUM AND JEJUNUM ABNORMALITIES Foreign Body A large foreign body can cause a distinct hyperechoic interface with strong distal acoustic shadowing.8,35-37

FIGURE 13. Longitudinal axis view of a segment of small intestines of a dog diagnosed with intestinal pythiosis.

Note the heterogeneous and ill-defined structure of this eccentrically located mass (calipers).

Linear foreign bodies have a characteristic appearance as a result of the plication of the small intestines. Oftentimes, the linear foreign body itself is identified, forming a focal hyperechoic linear band seen centrally within the affected small intestinal lumen (FIGURE 14).36,38 The bowel proximal to an obstructive foreign body is typically dilated with fluid, gas, and possible food material, whereas the bowel distal to the obstruction is empty or normal. If a foreign body is suspected in a dog with dilated segments of small intestine,

A

B

FIGURE 14. Longitudinal axis views of segments of small intestines from two dogs diagnosed with linear foreign body obstruction (A, B). Note the plicated appearance of the small intestinal loop (black arrowheads), which is pathognomonic for a linear foreign body.

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FIGURE 15. Transverse axis view of the ileocolic junction of a dog diagnosed with an ileocolic intussusception (calipers) with focal muscularis thickening (white arrow), likely due to infiltrative disease that was histopathologically confirmed to be lymphoplasmacytic enteritis.

CLINICAL INSIGHTS

following the dilated loops of small intestine will facilitate detection of the foreign body.

Circumferential loss of the normal, hyperechoic submucosal layer has been shown to represent extensive submucosal ulceration and necrosis, correlated with a greater likelihood of perforation, in humans with appendicitis.39,40

Intussusception Most intussusceptions occur in young dogs and are secondary to viral, bacterial, and parasitic etiologies.

In older dogs or cats, intussusceptions are often triggered by focal infiltrative disease of the intestine, such as neoplasia, and the intestinal wall in the vicinity of the intussusception should be carefully scrutinized to rule out such conditions (FIGURE 15).

An intussusception has a multilayered appearance in longitudinal axis and a concentric ring appearance (“bullseye pattern”) in transverse axis (FIGURE 16).8,35,37,41,42

Lymphangiectasia Lymphangiectasia is pathologic dilation and rupture of lymphatic vessels with leakage of lymphatic contents.

Intestinal changes consistent with lymphangiectasia include a combination of intestinal wall thickening, linear areas of striated hyperechogenicity of the small intestinal mucosal layer that are perpendicular to the long axis of the intestine, small intestinal wall corrugation, indistinct small intestinal wall layering, and small intestinal hypermotility (FIGURE 17).43,44

Intussusceptions are named according to the segments involved. Jejuno-jenunal, ileocolic, and cecocolic (cecal inversion) intussusceptions are the most common types.

A

FIGURE 17. Longitudinal axis view of a segment of duodenum of a dog diagnosed with histopathologically confirmed lymphangiectasia. Note the perpendicularly oriented hyperechoic striations within the mucosal wall of the duodenum.

These hyperechoic striations represent dilated lacteals.

B

FIGURE 16. Longitudinal (A) and transverse axis (B) views of a segment of small intestines of a dog diagnosed with intussusception. The intussusceptum (calipers) is a portion of the small intestines that telescopes into the intussuscipiens (brackets). In other words, the intussuscipiens is the recipient of the intussusceptum. Note the multilayered appearance to this segment of small intestine and the demarcation between the intussuscipiens and intussusceptum with the mesenteric fat (M) in the center.

FIGURE 18. Longitudinal axis view of a segment of jejunum of a dog diagnosed with carcinoma using cytology. Note the severe focal thickening and loss of wall layering forming a heterogeneous hypoechoic mass (calipers). The lumen is the hyperechoic interface with distal reverberation artifact and dirty shadowing.

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Concurrent anechoic peritoneal effusion may be present due to hypoproteinemia secondary to proteinlosing enteropathy.

Duodenal and Jejunal Wall Thickening Focal wall thickening with a loss of wall layering are commonly seen with intestinal focal neoplasia (FIGURE 18).14,35,45,46 The most common intestinal tumors of dogs are leiomyosarcoma, lymphoma, and adenocarcinoma.47-50 Smooth muscle tumors

of the intestines, such as leiomyosarcoma, often appear as large masses, eccentrically projecting from the intestinal wall, containing single or multiple hypo- or anechoic regions.50 Carcinoma is a localized, irregular, often mixed echogenicity thickening of bowel wall with a loss of layering;51 it can also present as an annular, constrictive lesion (FIGURE 19) that might be difficult to see on ultrasound, due to the gravel sign surrounding the area caused by the chronic partial obstruction.

Although more common in the large intestine, gastrointestinal stromal tumors can also be seen in the small intestine.52 No unique features of gastrointestinal stromal tumors have been recorded to differentiate from other gastrointestinal spindle cell tumors.52

A

FIGURE 19. Longitudinal axis view of a segment of jejunum of a dog diagnosed with cytologically confirmed carcinoma.

Note the irregularly marginated, heterogeneous thickening of the jejunum (calipers), and the eccentric, irregularly shaped, heterogeneous mass (ď&#x192;?). This eccentrically located mass causes constriction of the lumen; the hyperechoic lumen can be identified orad (proximal) to the lesion but disappears aborad (distal) to the level of the mass.

B

FIGURE 20. Transverse axis view of a segment of jejunum of a cat diagnosed with multicentric lymphoma. Note the severe jejunal wall thickening (calipers), measuring 0.5 cm, and the severely thickened muscularis layer (ď&#x192;?). The lumen of this segment of jejunum contains gas and echogenic fluid.

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FIGURE 21. Transverse axis view of a segment of jejunum (A) and longitudinal axis view of the right colic lymph node (B) of a cat diagnosed with cytologically confirmed, multicentric lymphoma. Note the hypoechoic mass with complete loss of wall layering circumferentially surrounding the segment of jejunum that measures 0.78 cm in wall thickness. The hyperechoic mucosal-luminal interface within the center of this mass demarcates the gas within the small intestinal lumen. The right colic lymph nodes are rounded, hypoechoic, and severely enlarged, measuring up to 0.8 cm in thickness.

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PEER REVIEWED

Elizabeth Huynh Elizabeth Huynh, DVM, is a diagnostic imaging resident and graduate student at University of Florida College of Veterinary Medicine. Her interests include ultrasonography, cross-sectional imaging, and nuclear medicine. She received her DVM from Ross University, finished her clinical year at Ohio State University, and completed a diagnostic imaging internship at Animal Specialty and Emergency Center in Los Angeles, California.

Clifford R. Berry Clifford R. Berry, DVM, DACVR, is a professor of diagnostic imaging at University of Florida College of Veterinary Medicine. His research interests include cross-sectional imaging of the thorax, nuclear medicine, and biomedical applications of imaging. He received his DVM from University of Florida and completed a radiology residency at University of Californiaâ&#x20AC;&#x201C;Davis.

In cats, common intestinal tumors include lymphoma and adenocarcinoma. Mast cell tumor and hemangiosarcoma have also been reported in the cat.44-47 Multicentric small intestinal neoplasia, particularly lymphoma, has moderately to severely thickened walls53 with muscularis layer thickening (FIGURE 20).54 Muscularis layer thickening is not definitive in diagnosing infiltrative neoplasia as it is also seen in cats with inflammatory bowel disease; however, it has been determined that the odds are high for a cat with muscularis thickening to have lymphoma.54 Thickening of the muscularis may be explained by the fact that lymphoma commonly occurs in conjunction with inflammatory bowel disease in cats,54 as chronic gastrointestinal inflammatory processes in cats can transform to develop subsequent gastrointestinal lymphoma.55

Additional imaging findings of lymphoma include circumferential, homogeneous, hypoechoic thickening of the small intestinal walls with a loss of normal wall layering;45 regional, moderate, hypoechoic lymphadenopathy is generally present (FIGURE 21). A complication of infiltrative intestinal neoplasia includes mechanical obstruction due to intraluminal narrowing.

Common inflammatory bowel diseases, such as lymphocytic-plasmacytic enteritis, are usually associated with mild to moderate wall thickening affecting several or all intestinal segments with variable severity. Other ultrasonographic features of intestinal inflammatory diseases include circumferential, mild to moderate wall thickening affecting primarily the mucosa, submucosa, and/or muscularis layers (FIGURE 22);54 diffuse increased echogenicity of the mucosa; or the presence of bright mucosal speckles.45,56 The bright mucosal speckling has been postulated to represent a section through dilated lacteals or focal accumulation of mucus, cellular debris, proteins, and/or gas within the mucosal crypts.57 There is significant overlap between the ultrasonographic appearance of inflammatory bowel disease and small cell lymphoma in cats, and the differentiation between these two entities is often impossible based on ultrasound findings alone.53,54 The presence of large, rounded hypoechoic mesenteric lymph nodes should be evaluated for potential multicentric disease (lymphoma or pythiosis) or metastatic disease (adenocarcinoma).

In dogs, intestinal tumors have significantly greater wall thickness, loss of wall layering, and more focal lesions than seen with enteritis.45 However, the absence of wall thickening does not completely rule out inflammatory disease as the correlation between wall thickness and histopathological diagnosis of inflammatory bowel disease in dogs have not been seen.58 To obtain a definitive diagnosis, histopathology of the affected area is required.59

SUMMARY

FIGURE 22. Longitudinal axis view of a segment of jejunum of a cat diagnosed with histopathologically confirmed inflammatory bowel disease. Note the mild, diffuse thickening of the wall, measuring 0.3 cm in thickness, with thickening of the muscularis layer.

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A systematic examination of the gastrointestinal tract is a routine part of the complete ultrasonographic abdominal evaluation. In Part 1 of the gastrointestinal tract, the normal and common abnormal ultrasound findings of the stomach, duodenum, and jejunum have been presented. The ileum, cecum, and colon will be addressed in Part 2.

To see the references for this article, please visit tvpjournal.com.

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Action step Watch the video on my website and begin implementing the concepts and tips outlined that will enable you to better manage your time: laurabaltodano.com/5-top-time-management-tips.

FINDING BALANCE

FINDING BALANCE

Time Management Laura Baltodano, Owner of Lighthouse Pet Clinic Lehigh Acres, Florida shutterstock.com/iofoto

The number 1 reason I hear from my clients about not taking care of themselves is lack of time: that existential, elusive work–life balance. The reality is that we all have the same number of hours available to us in a day. Have you considered how you are spending your time when you are not working?

Self-care is critical to overall happiness and fulfillment in both life and career. When you take better care of yourself, every aspect of your life begins to become more clear, you develop a better attitude, and you respond differently to obstacles and unexpected events that come up in your day-to-day life. The increased confidence you experience helps you

Laura Baltodano Dr. Laura Baltodano graduated in 2013 from Washington State University. She is the owner of Lighthouse Pet Clinic in Lehigh Acres, Florida. In addition to veterinary medicine, Dr. Laura is passionate about equipping others with tools to enhance their wellbeing. She is a certified health and wellness coach, a certified 7 Minute Life Time Management Trainer, registered yoga teacher, mindfulness teacher and is licensed to teach The Four Elements of Success by Lori Beth Jones. She loves singing, kayaking, reading and archery and enjoys spending time with her husband, 4 children and 9 pets.

become a better team player, clinician, parent, significant other, and friend because you feel better about yourself. In our profession, it can be too easy to become overwhelmed by what we need to do each day to care for our patients; we end up putting our own needs aside. Over time, that will be detrimental to your overall well-being. It is time to reconnect with your own individual needs in mind, body, and spirit.

One strategy to begin creating that time you need for self-care is considering your daily schedule and where you can create that “Happy Hour” before your day gets started. Depending on your schedule, it may be that it changes week to week.

That is okay. Remember that it is not about being perfect, but the key is being intentional and taking those first steps in developing a new habit. Studies show that developing a new habit, where performing a task becomes routine and second nature, takes 6 months. Be kind to yourself and know that it is a process; however, it is absolutely attainable.

When you begin developing a new routine to incorporate self-care, let those who are close to you know or have an accountability buddy. Explain why it is important to you so that they can keep you on track on days you “don’t feel like it.” They happen to everyone, so it is best to be prepared in advance with a strategy when they occur.

Taking time for yourself each day is not selfish—it is essential to living your true potential.

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