The Modern Equine Vet June 2017

The Modern

Equine Vet www.modernequinevet.com

Rabies Vaccine:

Do Horses Need One Every Year?

FDA Makes Label Changes to Critical Care Meds Pastern Arthrodesis Looking at Laminitis in a New Way Technician Update: End Stage Liver Failure

Vol 7 Issue 6 2017

TABLE OF CONTENTS

INFECTIOUS DISEASES

Do Horses Need Rabies

CDC/ Dr. Daniel P. Perl

4 Vaccine Boosters Every Year?

Cover photo: Shutterstock/Erik Mandre

NEWS

FDA Makes Label Changes to Critical Care Medications................................................. 3 ORTHOPEDICS

Return to Soundness After Pastern Arthrodesis............................. 8 NUTRITION

Looking at Laminitis in a New Way.....................................................12 TECHNICIAN UPDATE

Case Study: End Stage Liver Failure ...................................................16

ADVERTISERS Shanks Veterinary Equipment...............................3 Standlee Premium Western Forage......................5 Merial Marquis.......................................................7

Merck Animal Health...........................................11 Merial Equioxx.....................................................13 AAEVT............................................................................17

CONTACT MATT TODD TO ADVERTISE TODAY.

The Modern

Equine Vet SALES: Matthew Todd • ModernEquineVet@gmail.com EDITOR: Marie Rosenthal • mrosenthal@percybo.com ART DIRECTOR: Jennifer Barlow • jbarlow@percybo.com CONTRIBUTING WRITERS: Paul Basillo • Kathleen Ogle COPY EDITOR: Patty Wall Published by PO Box 935 • Morrisville, PA 19067 Marie Rosenthal and Jennifer Barlow, Publishers PERCYBO media  publishing

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NEWS NOTES

FDA Changes Label to Critical Care Medications The FDA is requiring labeling changes to three critical care medications that are approved for use in people and are also used in animals in the practice of veterinary medicine.

Veterinarians who use these products in animals should be aware of these changes, the agency said.

The labeling changes affect epinephrine, isoproterenol hydrochloride and neostigmine methylsulfate injections.

The FDA is requiring drug manufacturers to remove ratio expressions of strength (such as 1:1,000 and 1:10,000) from the labeling of these products.

Strength will now be expressed only as the amount per unit of volume (mg/mL). For example, once these changes are made, the labeling for an epineph-

The changes affect injectable epinephrine, isoproterenol hydrochloride and neostigmine methylsulfate.

NAME

RATIO

AMOUNT PER UNIT OF VOLUME

Epinephrine Injection, USP

1:1,000 1:10,000

1 mg/mL 0.1 mg/mL

Isoproterenol Hydrochloride Injection, USP

1:5,000

0.2 mg/mL

Neostigmine Methylsulfate Injection, USP

1:1,000 1:2,000

1 mg/mL 0.5 mg/mL

bels for drug storage bins are updated to reflect this change, the FDA recommended.

Veterinarians and technicians might already be seeing the revised drug labeling as companies have started making this change.

MeV

Lifting Large Animals Since 1957

rine injection, USP, 1:1,000 will state epinephrine injection, USP, 1 mg/mL. Several reports of medication errors in human patients indicated that medication strength expressed as a ratio on product labeling was confusing to health care providers and contributed to the errors. Most of the medication error reports described health care providers selecting epinephrine injection 1:1,000 (1 mg/mL) instead of the intended epinephrine injection 1:10,000 (0.1 mg/mL).

In 30% of the cases, individuals specifically stated that the ratios contributed to the errors. Some of the medication errors resulted in serious adverse outcomes, including death.

The United States Pharmacopeia (USP) instituted a new labeling standard to reduce medication errors related to confusion with ratio expressions.

What should veterinarians do?

Veterinarians and their technicians should start prescribing, communicating, dispensing and labeling these drugs in mg/mL rather than ratios, as well as review systems and processes to ensure order sets, protocols, references, dispensing labels and la-

www.shanksvet.com • info@shanksvet.com ModernEquineVet.com | Issue 6/2017

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INFECTIOUS DISEASE

Do Horses Need

Rabies Vaccine Boosters Every Year?

Maybe not, but public health dictates are unlikely to change.

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Shutterstock/Erik Mandre

Horses are one of the few

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animal species that require annual rabies boosters, but research

by W. David Wilson, BVMS, MS, DACVIM (Hon), and others suggests that maybe they really don’t.

“The vaccine debate has raged for many years, but there is an increasing body of evidence that protective antibody titers persist for three years for many pathogens included in vaccines,” said Dr. Wilson.

Why not equine rabies vaccine?

Dogs and cats require a rabies vaccine every two or three years, not annually, so equine veterinarians are constantly fielding questions from owners wanting to know why the requirements are different for horses.

“If the revaccination interval for rabies vaccine could be extended beyond one year, that would result in a lower cost to the client, lower risk of vaccine associated reactions, improved client compliance and

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improved client satisfaction,” he said, adding, “I think there is a place for titer determinations and revaccinating for rabies based on titer.”

The duration of persistence of antibody levels, the effect of repetitive vaccination and the effect of age on the effectiveness of rabies vaccination is unknown, he said.

But horses do occasionally suffer local and systemic reactions to vaccination and the cost of annual revaccination is borne by owners.

In the United States, rabies is found mostly among wildlife. In 2014, there were 6,000 confirmed cases reported in this country, of which 93% were in wildlife. Domestic animals accounted for 47.9% of all animals submitted for

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testing but only 7.37% (n = 445) of all rabies cases.

Only 25 cases occurred among horses, and the states with the greatest number of rabid horses were Texas (11 [44%]), Oklahoma (5 [20%]), Kansas (2 [8%]) and Pennsylvania (2 [8%]).

“There are about 9 million horses in this country,” he said, so you don’t have to be a statistician to recognize that the prevalence of rabies in horses is very low.

Rabies can mimic a number of neurologic and non-neurologic diseases. Dr. Wilson said the first case he saw in 1975 was referred for a colic work up, and his second case was a horse with intermittent lameness.

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INFECTIOUS DISEASE But rabies is a killer with no known cure and can be transmitted though animal bites to humans. So, many domestic animals, including horses, are vaccinated against rabies to protect human health.

“The primary reason for vaccinating horses against rabies is the reduction of public health risk and close—but maybe second to that is—the protection of horses themselves against what is an uncommon disease,” Dr. Wilson said.

Rabies vaccine is labeled for the vaccination of healthy horses, 12 weeks and older. It is recommended to administer one dose and then revaccinate annually thereafter. The American Association of Equine Practitioners lists rabies as a core vaccine for all horses and recommends annual boosters.

No one knows the minimum protective titer of rabies antibody in the horse, but he said a cutoff of 0.5 IU/mL is considered protective for other animals and was a good rule of thumb for horses.

The duration of rabies antibody response to vaccination was tested in a study led by Alison M. Harvey, BVSc, MRCVS, in which Dr. Wilson was a participant.

“The hypothesis was that the vaccine induced rabies virus neutralization antibody titer in repetitively vaccinated horses would remain higher than the levels predicted to be protective for longer than one year,” he explained. In addition, they wanted to test whether postvaccination antibody levels would remain high in geriatric horses, those 20 years or older.

They vaccinated 48 light breed horses from three premises placed into two groups: 28 were less than 20 years of age and 20 were older than 20 years.

Serum samples were collected before vaccination, at three to seven weeks after vaccination and at six-month intervals for two to three years. (A couple of the older horses were lost after two years.)

A high number of the horses had been vaccinated previously, he said, and they had measurable antibody before vaccination.

Three weeks after vaccination, 96% had protective titers; over three years, 86% still had protective titers. Although for most older horses, titers remained, two did not show any response. They had no measurable titers, but 17 had titers above 0.5 IU/mL, according to Dr. Wilson. “The percent that kept high titers even in the older horses was above 90%,” he said, adding that there was no statistical evidence of a reduced response in older horses.

Dr. Wilson has been working on another rabies project that has similar findings. He has been following 11 mares for many years and has found that 9.5 years after vaccination, all of the mares maintained a rabies-neutralizing antibody (RVNA) titer above 0.5 IU/mL. A challenge study presented at the AAEP meeting in 2009 by Craig Barnett, DVM, provided evidence that 0.5 IU/mL may be a conservative lower RVNA cut-off for protection of horses against rabies. In that study, horses were

protected when challenged with virulent rabies virus 14 months after receiving one dose of an inactivated rabies vaccine, even though the RVNA titer in these horses at the time of challenge was less than 0.5 IU/mL. “Most horses seroconvert in response to one dose of rabies vaccine and are primed,” Dr. Wilson said. Administration of a second dose about one year later creates a robust and persistent response in almost all horses. Prolonged persistence of antibody above the 0.5 IU/mL protective level suggests that annual vaccination of already primed horses is probably overkill.”

There is a possibility that horses could receive their primary dose and a booster one year later and then potentially be revaccinated at an interval of three years, as in other species. Measuring titers may be helpful in determining the appropriate revaccination interval, particularly for horses that have reacted adversely to rabies vaccination in the past, he said.

However, without challenge studies to document more prolonged protection, vaccine labeling cannot claim that protection lasts more than one year. And public health authorities must use this information to define a “currently vaccinated” horse from the perspective of recommendations for quarantine in the event that a human is bitten by a horse. Therefore, the AAEP includes annual rabies revaccination, he explained at the AAEP 62nd annual convention and trade show in Orlando.

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For more information: Harvey AM, Watson JL, Brault SA, et al. Duration of serum antibody response to rabies vaccination in horses. J Am Vet Med Assoc.

2016;15:249:411-418. http://avmajournals.avma.org/doi/abs/10.2460/javma.249.4.411?url_ver=Z39.88-2003&rfr_ id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed Barnett DC, Mellencamp WM, Lakshmanan L, Zhang S. Efficacy and duration of immunity of an inactivated equine rabies vaccine.

Presented at the 2009 AAEP Annual Meeting . 2009 AAEP Proceedings (vol 55); p. 177.

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MARQUIS® (15% w/w ponazuril) Antiprotozoal Oral Paste

Some diagnoses

you have to face head-on.

Equine Protozoal Myeloencephalitis (EPM) is an expert in deception and your clients may at first confuse it with other issues, such as lameness. Only stopping the parasite responsible can stop EPM from causing further damage to the horse’s brain and CNS. Time matters. The sooner EPM is detected and diagnosed, the better the chance for recovery.

That’s why you need a tube of MARQUIS on every truck to initiate treatment immediately. MARQUIS is a powerful anti-protozoal.

Only MARQUIS offers a 3X loading dose protocol that allows it to reach steady state in 24 to 48 hours.*,1 *Clinical relevance has not been determined.

The signs can be subtle.

The treatment should be aggressive.

Clients can save on their next purchase.

MAX.merial.com MARQUIS Freedom of Information Summary and Supplement and product label.

1

IMPORTANT SAFETY INFORMATION: The safe use of MARQUIS in horses used for breeding purposes, during pregnancy, or in lactating mares, has not been evaluated. In animal safety studies, loose feces, sporadic inappetence, lost weight, and moderate edema in the uterine epithelium were observed.

Merial is now part of Boehringer Ingelheim. ‰MARQUIS is a registered trademark, and ™MAX, Merial Awards Xpress is a trademark, of Merial. ©2017 Merial, Inc., Duluth, GA. All rights reserved. EQUIOMQ1506-B (04/16)

ORTHOPEDICS

MARQUIS

®

(15% w/w ponazuril) Antiprotozoal Oral Paste

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

For The Treatment Of Equine Protozoal Myeloencephalitis (EPM) In Horses For Oral Use Only BRIEF SUMMARY Before using MARQUIS, please consult the product insert, a summary of which follows: INDICATIONS MARQUIS (ponazuril) is indicated for the treatment of equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona.

WARNINGS For use in animals only. Not for use in horses intended for food. Not for human use. Keep out of reach of children.

PRECAUTIONS Prior to treatment, a complete neurologic exam should be completed by a veterinarian. In most instances, ataxia due to EPM is asymmetrical and affects the hind limbs. Clinicians should recognize that clearance of the parasite by ponazuril may not completely resolve the clinical signs attributed to the natural progression of the disease.

The prognosis for animals treated for EPM may be dependent upon the severity of disease and the duration of the infection prior to treatment. The safe use of MARQUIS (ponazuril) in horses used for breeding purposes, during pregnancy, or in lactating mares, has not been evaluated. The safety of MARQUIS (ponazuril) with concomitant therapies in horses has not been evaluated.

ADVERSE REACTIONS In the field study, eight animals were noted to have unusual daily observations. Two horses exhibited blisters on the nose and mouth, three animals showed skin reactions for up to 18 days, one animal had loose stools, one had a mild colic on one day and one animal had a seizure while on medication. The association of these reactions to treatment was not established.

ANIMAL SAFETY SUMMARY MARQUIS (ponazuril) was administered to 24 adult horses (12 males and 12 females) in a target animal safety study. Three groups of 8 horses each received 0, 10 or 30 mg/kg (water as control, 2X and 6X for a 5 mg/kg [2.27 mg/lb] dose). Horses were dosed after feeding. One half of each group was treated for 28 days and the other half for 56 days followed by necropsy upon termination of treatment. There were several instances of loose feces in all animals in the study irrespective of treatment, sporadic inappetence and one horse at 10 mg/kg (2X) lost weight while on test.

Loose feces were treatment related. Histopathological findings included moderate edema in the uterine epithelium of three of the four females in the 6X group (two treated for 28 days and one for 56 days).

For customer care or to obtain product information, including a Material Safety Data Sheet, call 1-888-6374251 Option 2, then press 1.

Return to Soundness After

Pastern Arthrodesis When Aimee Swenson began the search for a new trail horse, her bar was set high. It seemed no one could quite fill the horseshoes of her previous partner of 14 years, a retired mounted police horse named Bunky.

“He was pretty much perfect,” said Ms. Swenson.

“After losing him at age 28, I spent a whole year looking for my next horse—one that I could enjoy as much as my first.”

Then she found Netty.

Ms. Swenson made the trip from Ashland, Va. to Ocean City, Md. to meet the chestnut and white Paint, and he quickly won her over with his inquisitive, friendly disposition. It wasn’t long before Netty came home with her, and they explored many trails together over the next several years. While a smart and careful riding partner, it is the way Netty acts with Ms. Swenson out of the saddle that she truly adores. “He is a bit of the youngest child. When you ask him to do something, he always asks

The prognosis for returning to soundness with pastern arthrodesis is only about 70%, but the owner thought the investment was worth it.

®MARQUIS is a registered trademark of Merial. ©2016 Merial, Inc., Duluth, GA. All rights reserved.

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‘why?’” laughs Swenson.

“But I wanted a horse with personality and I got just that. He really loves people and attention and is just a great boy.”

A Sore Subject

The one challenge Ms. Swenson had with Netty concerned pastern arthritis in his lower left front leg, which grew increasingly uncomfortable for the Paint over time.

Eventually joint injections were administered and seemed to successfully manage his pain for almost a year. Then, in March 2016, even the injections began proving ineffective—not even lasting 30 days. Ms. Swenson and her long-time vet, Douglas Daniels, DVM, of Virginia Equine PLLC, had to come up with a new plan.

Ms. Swenson was given two options: let Mother Nature take its course, knowing that the joint would eventually fuse on its own in maybe six to 12 months

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or have the joint surgically fused with a pastern arthrodesis. Unfortunately, she was told it was difficult to predict how long the joint would take to naturally fuse, and radiographs showed that there were still very little signs of fusion.

By then Ms. Swenson was managing Netty’s comfort level with a combination of phenylbutazone, firocoxib, topical anti-inflammatories, chiropractic care and daily icing, but the horse was still quite lame. “We x-rayed his other legs and feet since we were concerned those joints had started breaking down as well, but there were no signs of arthritis anywhere else,” said Ms. Swenson. “At that point I thought if we could fix this one joint, Netty could at least return to comfortable turnout. He had been very patient and I didn’t want to make him wait in pain any longer.

I felt that at 16 he was young and healthy enough to invest in the surgery.”

Photos courtesy of New Bolton Center

Locking It In

Aimee and Netty

Pastern arthrodesis has an approximately 70% prognosis for return to soundness. Ms. Swenson interviewed a number of surgeons, including several local to her area in Virginia, but ultimately made her decision after speaking with New Bolton Center’s Kyla Ortved, DVM, PhD, assistant professor of Large Animal Surgery. “I felt the most comfortable with how Dr. Ortved answered my questions, and I also knew that New Bolton Center has a fabulous reputation. I decided it was worth the trip.”

Ms. Swenson and Netty made the five-hour trek to New Bolton Center’s Kennett Square, Penn. campus in mid-September for the surgery Dr. Ortved performed the pastern arthrodesis via an open technique using inverted “T”and “V”-shaped incisions made ModernEquineVet.com | Issue 6/2017

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Photos courtesy of New Bolton Center

ORTHOPEDICS

Except for pastern arthrodesis: Dr. Ortved performed the pastern arthrodesis was performed through an open technique using inverted “T”- and “V”-shaped incisions made across the front of the pastern to access the joint and remove the damaged cartilage. A specialized three-hole locking compression plate was then placed with three transarticular screws across the face of the joint to stabilize it and support healing of the soft tissue around it.

Sweet Relief

The surgery went according to plan, and the change in Netty’s pain level was almost immediate.

Netty’s left front leg was placed in a cast to help keep the joint stable while the incision healed. He 10

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quite well, so we sent him home with Aimee to continue his rehab there,” Dr. Ortved said.

Netty transitioned to at-home care smoothly, and within two weeks, no longer needed bute or firocoxib to be comfortable. Radiographs were taken at three months and six months postop, and both Drs. Ortved and Daniels were very happy with the progress. Throughout his rehab, Netty remained an amenable patient, and returned to turnout with his pasture mate in March 2017.

Exceeding Expectations Already

Photos courtesy of New Bolton Center

across the front of the pastern to access the joint and remove the damaged cartilage. A specialized three-hole locking compression plate was then placed with three transarticular screws across the face of the joint to stabilize it and support healing of the soft tissue around it.

New Bolton Center’s surgeons now routinely use the locking compression plate for arthrodesis, a technology that has emerged within the last 15 years. Traditional non-locking bone plates use normal cortical bone screws that are placed through the plate into the bone, whereas locking compression plates use special screws with heads that secure into the plate itself.

“This creates a much sturdier and more stable fixation, with less potential for movement,” explained Dr. Ortved. “In particular, the shorter three-hole locking compression plate implant, with holes that are perfectly positioned to place across the pastern joint, has really helped fine-tune the pastern arthrodesis surgery.”

Sweet relief

stayed under New Bolton Center’s care for the next two weeks and continued to remain very comfortable on the limb.

Once the cast was removed, postoperative radiographs were taken, which confirmed excellent placement of the implant. “At that point he was still recovering

Netty continues to progress in soundness and is almost fully sound at the walk and trot today.

“He is not 100% sound all of the time quite yet, but he is so much more comfortable and can happily canter around the field when he wants. My vet said he has no reason to doubt that he will continue to improve over the next several months,” said Ms. Swenson.

“If he recovers to full soundness, I might get on him again, or I might not. My reason for doing this surgery was to do what was fair for him. With his pain level at the time, my only other option would have been to put him down.

That just didn’t feel like the right decision. Now he can hopefully live 10 more years comfortably and doing what he wants.”

MeV

Safety In Numbers Some dewormers claim just one dose of their product is the best way to deworm your horse, but that’s simply not true.

Demand Safety: You won’t find a laundry list of warnings and precautions on the PANACUR® (fenbendazole) POWERPAC label because fenbendazole has a unique mode of action that makes it safe for horses of all ages, sizes, and body conditions.

Demand Efficacy: PANACUR® POWERPAC is the only dewormer FDA approved to treat ALL STAGES of the encysted small strongyle.1 Other dewormers miss a critical stage, EL3, which can account for up to 75% of the encysted small strongyle burden. Plus, it’s the best choice for treating ascarids — which are not just a problem in young horses!

So when it comes to which dewormer to trust, don’t forget there’s safety in numbers.

Consult your veterinarian for assistance in the diagnosis, treatment and control of parasitism.

Do not use in horses intended for human consumption. When using PANACUR® (fenbendazole) Paste 10% concomitantly with trichlorfon, refer to the manufacturers labels for use and cautions for trichlorfon.

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PANACUR® (fenbendazole) POWERPAC Equine Dewormer product label.

The Science of Healthier Animals 2 Giralda Farms • Madison, NJ 07940 • merck-animal-health-usa.com • 800-521-5767 Copyright © 2017 Intervet Inc., d/b/a/ Merck Animal Health, a subsidiary of Merck & Co., Inc. All rights reserved. 3654 EG-PC-Adver

NUTRITION

Looking at

Laminitis

Early identification of which horses are at risk may be crucial in reducing the burden of disease

IN A NEW WAY

Shutterstock/ultimathule

What most equine veterinar-

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offered Dr. Coleman, assistant professor of large animal internal medicine at Texas A&M University. “Today [in human medicine] we are finding that what people eat and how much they exercise do not give all the answers. The same may be true in horses; the tendency of some horses to gain weight may not simply be a function of diet and exercise.”

Perhaps veterinarians should look at laminitis in a different way, suggested Dr. Coleman.

What makes a horse obese? And what if obesity is a symptom of a much bigger problem?

ians have suspected for decades is starting to pan out; veterinarians are finally strengthening the evidence that early identification of horses at risk for obesity and endocrinologic disease can be key in beating the odds of laminitis, explained Michelle Coleman, DVM, PhD, DACVIM, lead researcher of a four-year case-control study designed by the AAEP Foundation Laminitis Research Working Group.

“I venture to say that conventional wisdom of diet and exercise might not be the whole story,”

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“The initiating events of laminitis occur before the onset of clinical signs of disease, making it a challenging disease to study and a challenging disease to prevent,” she said.

An estimated incidence of up to 34% of horses and 13% of horse operations are annually affected, with a lifetime risk for laminitis estimated at 15%. Thus, there are significant clinical and economic effects associated with laminitis.

Old versus new

Laminitis research traditionally has centered on experimental induction of the disease. “These

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ain Because managing OA p . in a p re o m e s u a c ’t n ld u o sh ty profile.

with EQUIOXX delivers efficacy

an exceptional safe

arthritis pain and right choice for treating osteo the is XX UIO EQ d fin l u’l yo , When you do the research . inflammation for your clients X-1 AID for horses – spares CO

NS XX – the first and only coxib • First and Only – EQUIO 1 n phenylbutazone, including while inhibiting COX-2 * 2 ective or more effective tha eff as ed rat s wa XX UIO EQ dy, overall improvement scores and e enc fer um • More Effective – In a stu circ t join , 3,4 nipulation, range of motion improvement in pain on ma n any other NSAID; tha s die stu ety saf in ses n tested on more hor • Safety – EQUIOXX has bee ects most horses had no side eff compliance at the recommended dose, hours which can also aid in 24 to up n pai ls tro con e • Convenient – One dos been determined. *Clinical relevance has not

t to pasture. See how ou D AI NS d ol ur yo t pu to Time rence for your clients.

EQUIOXX can make a diffe

EQUIOXX.com

Available in three formulations to fit in and out of competition needs: Injection, Paste and Tablet.

IMPORTANT SAFETY INFORMATION: As with any prescription medication, prior to use, a veterinarian should perform a physical examination and review the horse’s medical history. A veterinarian should advise horse owners to observe for signs of potential drug toxicity. As a class, nonsteroidal anti-inflammatory drugs may be associated with gastrointestinal, hepatic and renal toxicity.

Use with other NSAIDs, corticosteroids or nephrotoxic medication should be avoided. EQUIOXX has not been tested in horses less than 1 year of age or in breeding horses, or pregnant or lactating mares. For additional information, please refer to the prescribing information or visit www.equioxx.com.

Data on file at Merial, Safety Study, PR&D 0144901.

Doucet MY, Bertone AL, et al. Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. J Am Vet Med Assoc. 2008;232(1):91-97.

3 EQUIOXX product labels and FOI summaries and supplements.

4 Data on file at Merial, Clinical Experience Report PHN 471, PR&D 0030701.

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Merial is now part of Boehringer Ingelheim. ®EQUIOXX is a registered trademark of Merial. ©2017 Merial, Inc., Duluth, GA. All rights reserved. EQUIEQX1607 (1/17)

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NUTRITION

Why Are Epidemiologic Studies Desirable?

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

Welfare Reasons – No new disease is induced Relevant Results – Findings are relevant to naturally occurring cases of disease Identify Risks – Risk factors for development of disease can (potentially) be identified Future Strategies – Based on risk factors, future management and prevention strategies can be determined Burden of Disease – Ultimately, the burden of disease can be reduced

EQUIOXX® (firocoxib) is indicated for the control of pain and inflammation associated with osteoarthritis in horses.

Firocoxib belongs to the coxib class of non-narcotic, nonsteroidal anti-inflammatory drugs (NSAID).

CONTRAINDICATIONS: Horses with hypersensitivity to firocoxib should not receive EQUIOXX. WARNINGS: EQUIOXX is for use in horses only. Do not use in horses intended for human consumption. Do not use in humans. Store EQUIOXX Tablets out of the reach of dogs, children, and other pets in a secured location in order to prevent accidental ingestion or overdose. Consult a physician in case of accidental human exposure.

Horses should undergo a thorough history and physical examination before initiation of NSAID therapy. Appropriate laboratory tests should be conducted to establish hematological and serum biochemical baseline data before and periodically during administration of any NSAID. NSAIDs may inhibit the prostaglandins that maintain normal homeostatic function. Such anti-prostaglandin effects may result in clinically significant disease in patients with underlying or pre-existing disease that has not been previously diagnosed.

Treatment with EQUIOXX should be terminated if signs such as inappetance, colic, abnormal feces, or lethargy are observed. As a class, cyclooxygenase inhibitory NSAIDs may be associated with gastrointestinal, renal, and hepatic toxicity. Sensitivity to drug-associated adverse events varies with the individual patient. Horses that have experienced adverse reactions from one NSAID may experience adverse reactions from another NSAID. Patients at greatest risk for adverse events are those that are dehydrated, on diuretic therapy, or those with existing renal, cardiovascular, and/ or hepatic dysfunction. The majority of patients with drug-related adverse reactions recover when the signs are recognized, drug administration is stopped, and veterinary care is initiated.

Concurrent administration of potentially nephrotoxic drugs should be carefully approached or avoided. Since many NSAIDs possess the potential to produce gastrointestinal ulcerations and/or gastrointestinal perforation, concomitant use of EQUIOXX with other anti-inflammatory drugs, such as NSAIDs or corticosteroids, should be avoided. The concomitant use of protein bound drugs with EQUIOXX has not been studied in horses. The influence of concomitant drugs that may inhibit the metabolism of EQUIOXX has not been evaluated. Drug compatibility should be monitored in patients requiring adjunctive therapy.

The safe use of EQUIOXX in horses less than one year of age, horses used for breeding, or in pregnant or lactating mares has not been evaluated. Consider appropriate washout times when switching from one NSAID to another NSAID or corticosteroid.

The Safety Data Sheet (SDS) contains more detailed occupational safety information. For technical assistance, to request an SDS, or to report suspected adverse events call 1-877-217-3543. For additional information about adverse event reporting for animal drugs, contact FDA at 1-888-FDA-VETS, or http://www.fda.gov/AnimalVeterinary.

Rev 10/2016

studies are valuable,” Dr. Coleman explained, “but experimental models may poorly replicate naturally occurring cases of the disease. Despite significant research, there is still no clear mechanistic pathway for how the disease occurs.”

In 2009, AAEP members identified laminitis as a top priority (63%) for research funding and investigation. With limited epidemiologic studies of laminitis, “we resolved to look at [it] from a different perspective.”

In 2011, the AAEP Foundation Laminitis Research Working Group launched a comprehensive four-year study in naturally occurring cases of laminitis by taking an epidemiologic approach. Epidemiologic studies are desirable for several reasons, said Dr. Coleman, including relevant study results from naturally occurring rather than experimentally induced cases of disease.

The research working group also decided to focus on the most common causes of laminitis seen in private practice: exposure to pasture, endocrinopathy and glucocorticoid administration.

“From there,” Dr. Coleman explained, “we designed a case-control study of pasture- and endocrinopathy-associated laminitis, which became known as PEAL.” This is the first reported observational study of veterinarian-diagnosed incident cases of PEAL in North America. But Dr. Coleman added, “we didn’t just identify risk factors, we identified modifiable risk factors for development of disease.”

The results are in

The study design reflected laminitis cases evaluated by AAEP veterinarians 14

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and followed backward in time to identify risk factors for development of disease. Cases were evaluated within four weeks of the onset of clinical signs. Two populations of controls were identified: healthy horses with no history of laminitis and horses lame in one front foot with no history of laminitis. Collected data included: • signalment • activity level • dietary history • pasture management • body morphometrics • hoof care and • steroid therapy.

In total, 7,100 veterinarians in North America were recruited and 625 agreed to participate, with 115 submitting data for the survey representing 32 US states and 3 Canadian provinces.

A total of 199 laminitic cases, 198 healthy controls and 153 lameness controls were included in the analysis.

Many variables were not associated with the development of disease, including gender, age and frequency of exercise.

Significant variables included dietary management, stable management and body morphometrics, along with historic diagnosis of endocrinopathic disease and recent administration of glucocorticoids.

Specifically, body morphometrics looked at body condition, generalized and regional adiposity, neck circumference, height and girth:height ratio.

Dr. Coleman stressed that all of these variables were significant with their model, with horses at increased odds of developing disease. The study confirmed that horses in obese body condition [BCS ≥7]

or with generalized and regional adiposity have increased odds of developing PEAL. In fact, Dr. Coleman added, fat accumulation in all adiposity sites put horses at increased odds of developing laminitis when comparing laminitic horses with healthy controls or lameness controls. Similarly, she said, the study looked at dietary management practices, including recent diet change. “We stratified the type of change into horses that had increased or decreased concentrate and found no difference. It appeared as though the change itself put these horses at risk of developing disease," said Dr. Coleman.

What the future holds

“How do we use this improved evidence and knowledge moving forward?” Dr. Coleman asked. Much of our past research has concentrated on looking at mechanistic pathways in answering why overweight or fat horses founder, she said. Using what we know today, how can we reduce the burden of laminitis by reducing the burden of obesity or adiposity?

Based on her clinical experience and the study’s findings, Dr. Coleman stressed the importance of early recognition of obese or overweight horses, as well as horses with endocrinopathic disease.

Likewise, client education is key to identifying at-risk horses earlier.

“Educating clients about the importance of obesity [in keeping their

horses healthy] is important,” Dr. Coleman explained, “since evidence has now established obesity as a key risk associated with laminitis.” But client education has traditionally been a giant uphill battle, she noted, adding that an overwhelming percentage of equine owners do not perceive weight gain as a health issue.

“We need to better engage our clients,” Dr. Coleman said, and offered a few tips, such as: • g iving clients easy-to-understand reasons why weight gain is so risky; • describing individualized feeding plans in detail; • implementing follow-up strategies so clients stay engaged; and • regularly monitoring each horse’s body weight.

Until now, equine veterinarians in North America had no supportive evidence to back what they all were thinking: that fat horses founder and endocrinopathic disease results in laminitis. “With this study,” Dr. Coleman said, “we now have [that] supportive evidence.”

Considering the extent of obesity being witnessed in horses today, Dr. Coleman emphasized it’s time to look at laminitis a new way by asking: What is a horse’s risk factor for obesity? The same approach applies to endocrinopathic disease, she added: “Identifying which horses are at high risk of developing endocrinopathic disease or becoming obese

Significant Findings Distribution by Breed – Thoroughbreds and warmbloods (including drafts) at decreased risk; miniatures and ponies at increased risk Stable Management & Feeding Practices – Lush pastures and recent stable change increased odds of developing disease; when this type of change was stratified, there were no apparent differences, only the fact that there was a stable change Dietary Management – Recent diet change increased risk for developing laminitis as compared with healthy controls; when type of change (increased versus decreased concentrate) was stratified, the change itself seemed to put the horses at risk Body Morphometrics – Body condition, generalized and/or regional adiposity, neck circumference, height, and girth:height ratio all affected risk for disease as compared with controls Endocrinopathic Disease – Pars pituitary intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) increased odds of developing disease as compared with both healthy and lameness controls Prior Administration of Glucocorticoids – Any glucocorticoid administered within 30 days of onset of clinical signs increased risk for disease may be key in reducing the burden of disease.”

There will be a whole new field for veterinarians to delve into, Dr. Coleman predicted.

MeV

For more information: Coleman M, Belknap J, Eades S, et al. Case-control study of pasture- and endocrinopathy-associated laminitis in horses. Proceedings of the AAEP 62nd Annual Convention. 2016;62.

McGowan TW, Pinchbeck G, Phillips CJC, Perkins N, Hodgson DR, McGowan CM. A survey of aged horses in Queensland, Australia. Part 2: clinical signs and owners' perceptions of health and welfare. Aust Vet J. 2010;88(12):465-471.

Moore RM, Bu MJ. Vision 20/20 – Conquer laminitis by 2020. J Equine Vet Sci. 2010;30(2):74-76.

USDA APHIS Veterinary Services. National Animal Health Monitoring System (NAHMS) Study: Lameness & Laminitis in U.S. Horses.

Fort Collins, CO: Center for Epidemiology and Animal Health, 2000.

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TECHNICIAN UPDATE

Case Study: End Stage Liver Failure Shana Lemmenes, CVT, VTS-EVN

Photos courtesy of Shana Lemmenes

A 13-year-old Quarter Horse gelding, presented to the University of Minnesota’s Equine Center during clinic hours on July 29, 2014. He was brought in for evaluation of liver disease and pastern dermatitis.

His pastern dermatitis had first appeared in early July and was treated with an antibiotic-anti-inflammatory topical ointment, leg wraps, of phenylbutazone once daily and rest for two weeks. His dermatitis healed well, and he was put back out to pasture 10 days prior to being admitted, but on July 22, his owners noticed that he had developed a stiff gait and had purulent crusting over the white skin on his legs (right front and both hind).

They also noticed dark, foul smelling urine and that he was lying down more frequently than normal.

On July 24, they noticed that his gait had become increasingly stiff, and that he had started dragging his feet when he walked. They called their primary veterinarian who performed a complete blood count and chemistry, which showed marked elevations in his liver enzymes (AST, GGT, and TBil). At that time

Standing in his stall on IV fluids (7/29/14)

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Hind leg dermatitis

he was started on a five-day course of sulfamethoxazole while awaiting a consult at the university.

He was inappetant for several days and refused to eat grain, which was highly abnormal for him. His owner reported that he usually had a ravenous appetite and minimal weight loss over the winter. However, this past winter had been particularly hard on him. He was down to 870 lbs, but gained some weight back in the spring. Despite the initial improvement in his weight, he had failed to put on much weight since May. In addition, he had five or six episodes of pastern dermatitis in the past, none of which were particularly severe. These episodes had usually involved the backs of his heels and had been completely resolved with treatment.

Depressed and unresponsive

On initial presentation, he was dull and depressed, but responsive. His mucus membranes were tacky, injected and icteric. His capillary refill time was greater than 2 seconds. A skin tent could be appreciated and Utah was estimated to be 7% dehydrated.

Although his vital signs (temperature, pulse and respiratory rate) were within normal limits, a clear nasal discharge was noted bilaterally. His eyes were clear with normal menace, palpebral and pupillary light reflexes. No murmurs or arrhythmias were noted on cardiac auscultation and his lung sounds were clear. Borborygmi (gut sounds) was normal in all four quadrants. His gait was very stiff, and he was dragging his hind feet. He had severe pastern dermatitis with crusting and purulent draining tracts.

The dermatitis was only present on the white areas of his legs. The affected areas were severely edematous and warm to the touch. He was especially sensitive about his left hind leg and would hold it up when touched. His coronary bands were soft and fluctuant. He had an acidic “ammonia-like� smell.

He urinated during the examination. His urine was brownish-red and smelled very foul. A urine specific gravity (USG) and dipstick were run. His USG was 1.024 and the dipstick showed a marked amount of bilirubin.

As the physical was performed and a full history was taken from the owner, the technicians drew blood for a packed cell volume (PCV) and total protein (TP), and CBC/chemistry, bile acids test and coagulation profile. Results from the blood work revealed that the PCV and TP and were increased at 49% and 8.0 g/dL respectively, indicating severe dehydration. The CBC

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TECHNICIAN UPDATE

Photos courtesy of Shana Lemmenes

showed that he had a mature neutrophilic leukocytosis with rare toxic change indicating inflammation and possibly infection. His fibrinogen was normal, which may have reflected an inappropriate response to systemic inflammation secondary to decreased production of fibrinogen by the liver.

He had increased red blood cells (RBCs) and hematocrit, most likely a relative polycythemia secondary to dehydration. His serum chemistry was a classic picture of liver dysfunction/failure: low BUN, low fibrinogen, hypoalbuminemia and hyperbilirubinemia. There was also severe hepatic cholestasis (increased bilirubin, ALP and GGT), severe hepatocellular damage (increased SDH and AST) and mild muscle damage (increased CK, likely due to trailering). His globulins were markedly increased, supporting the clinician’s suspicions of severe underlying inflammation and possibly infection.

There was evidence of a mild metabolic acidosis (decreased bicarbonate) that would need to be further evaluated via a blood gas. In addition to the

Liver as seen at necropsy

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CBC/chemistry we ran a bile acids test (which evaluates hepatobiliary function). Bile acids are excreted by the liver into the gastrointestinal tract and are increased in the serum when the liver is not functioning appropriately. His bile acids were markedly increased, further supporting the diagnosis of severe liver dysfunction.

A coagulation profile was also run at that time.

Since clotting factors are made in the liver, a coagulation profile can also be used to assess liver function.

Both his prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged, suggesting decreased production of clotting factors due to liver dysfunction. Based on the results of this test, extra precautions were taken when performing the liver biopsy, which was done next, guided by ultrasonography.

Biopsies

Three biopsies of his liver were taken with a 14-gauge True-cut biopsy instrument. Two of the biopsies were placed in formalin and submitted for histopathology.

The other biopsy was submitted for aerobic and anaerobic cultures. There was a small amount of bleeding between the body wall and peritoneal cavity noted following the biopsy; fortunately, his biopsy site clotted nicely and there was no evidence of deeper tissue hemorrhage.

The initial treatment plan included fluids to correct his dehydration. He was given a 10 L bolus of plasmalyte with 5% dextrose, followed by maintenance fluids at 1 L per hour (this was later increased to 2 L per hour when his PCV started to increase again). We also gave him flunixin meglumine to decrease inflammation and provide pain relief.

His legs were cold hosed every 12 hours for 20 minutes per leg, and he was fed a low-protein diet of free choice grass hay, and a mash of beat pulp, oats, bran and molasses (despite this palatable mash, his appetite declined again on July 30).

His condition worsened dramatically overnight on July 30. Despite the fact that his PCV initially decreased in response to fluid therapy, it began to rise again. He ate a small amount of food, but his mentation did not improve. The clinician increased his fluids to 2 L per hour and we continued monitoring him closely. This had no effect on his rising PCV and his mentation continued to decline.

At 11 p.m., he began circling compulsively. In addition he became increasingly ataxic and directionless in his pacing. The clinician was again contacted and asked to come take a look at him. The clinician arrived around 12 a.m., and we sedated him with IV xylazine.

After that, we continued to closely monitor him.

Teaching Points

At around 1:30 am, he began to stumble and showed signs of aggression (kicking violently whenever his hind legs touched the wall). Per the clinician’s instruction, I carefully sedated him with another dose of xylazine and detomidine (both intravenously and intramuscularly). This caused him to lie down, making it safer for us to work with him, and kept him from harming himself. The clinician called his owner and it was decided that he could not continue this way. His owners drove in, and with them present, he was euthanized around 3 a.m.

The results of the histopathology report showed chronic hepatocellular degeneration with necrosis and megalocytosis. This suggested a toxic hepatopathy. Possible sources of this include phytotoxins and mycotoxins.

Our senior clinician explained that his pastern dermatitis was likely caused by secondary photosensitization, which is associated with liver failure. After ingestion, chlorophyll is converted to a photodynamic agent called phylloerythrin, which is normally excreted from the body through the bile ducts in the liver. In an animal with a liver disease that disrupts this process, phylloerythrin is not properly excreted and accumulates in circulation. The compound is activated by UV light and thus causes severe inflammation in lighter pigmented skin (this is why the dermatitis only appeared on the white areas of the legs).

This is most commonly seen in the summer when sunlight is most intense and pastured horses are consuming green plants with high levels of chlorophyll.

Clover and alfalfa are the most common inciting feeds.

A diagnosis of photosensitization certainly fits the timeline of his clinical signs. He first developed severe pastern dermatitis when out on pasture in early July.

His clinical signs resolved with leg wrapping, topical

ointment and confinement to a round pen. One week after returning to pasture, he had another episode of pastern dermatitis and began showing signs of liver dysfunction. These signs ultimately progressed to hepatic encephalopathy. It is possible that his previous episodes of pastern dermatitis could have been related to underlying hepatic dysfunction that was not otherwise clinically apparent. This would suggest a chronic liver disease that progressed to full blown liver failure this summer, resulting in the clinical signs present. Differentials for liver disease include toxins (alslike clover, panicum grasses, pyrrolizidine alkaloids), cholangiohepatitis (bile duct inflammation or infection), Tyzzer’s disease (Clostridium piliforme), Theiler’s disease (serum hepatitis), chronic active hepatitis, hepatic or metastatic neoplasia, hepatic lipidosis, biliary stones and portal vein thrombosis.

Although we are certain that the diagnosis of endstage liver failure with hepatic encephalopathy is correct, and that this damage was likely caused by a toxin, it cannot be determined when or how long he was exposed to the hepatotoxin. The clinician recommended that the owners have their other horse’s liver enzymes tested; in addition, we recommended that they should regularly survey the pasture for toxic or unusual plants.

MeV Click here to read more about toxic plants.

Shutterstock/nelelena

Secondary photosensitization, which is associated with liver failure, can cause pastern dermatitis. After ingestion, chlorophyll is converted to a photodynamic agent called phylloerythrin, which is normally excreted from the body through the bile ducts in the liver. In an animal with a liver disease that disrupts this process, phylloerythrin is not properly excreted and accumulates in the body. The compound is activated by UV light and caused the dermatitis.

This is most commonly seen in the summer when sunlight is most intense and pastured horses are consuming green plants with high levels of chlorophyll. Clover and alfalfa are the most common inciting feeds.

It is possible that his previous episodes of pastern dermatitis could have been related to underlying hepatic dysfunction that was not otherwise clinically apparent. This would suggest a chronic liver disease that progressed to full blown liver failure, resulting in the clinical signs present.

In this case, the damage was most likely caused by a toxin. It is important for technicians to teach owners about toxic or unusual plants and caution them to regularly survey their pasture for them.

About the author

Shana Lemmenes, CVT, VTS-EVN, is a senior large-animal technician at the University of Minnesota. She is also a regional contact (Canada) for AAEVT and holds the Member at Large position with AEVNT. She enjoys spending time with her family, friends, dogs and horses.

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