Compendium Equine | October 2009

6 CE Contact Hours | CompendiumEquine.com | Peer Reviewed

Vol 4(8) October 2009

Therapeutics in Practice

Treating Cantharidin Toxicosis Acute Colitis

Re ca p

Clinical Snapshot

35 0

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October 2009 Vol 4(8)

CompendiumEquine.com | Peer Reviewed | Free CE

The AAEP’s Media Partnership Program is composed of an esteemed group of industry-leading media outlets dedicated to providing resources and education, through the AAEP, to veterinarians and horse owners to improve the health and welfare of horses.

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October 2009 Vol 4(8)

CompendiumEquine.com | Peer Reviewed | Free CE

EDITORIAL BOARD Michelle Henry Barton, DVM, PhD, DACVIM The University of Georgia Internal Medicine

EDITOR IN CHIEF James N. Moore, DVM, PhD Department of Large Animal Medicine College of Veterinary Medicine The University of Georgia Athens, GA 30602 706-542-3325 Fax 706-542-8833 jmoore@uga.edu

Gary M. Baxter, VMD, MS, DACVS Colorado State University Acupuncture, Surgery Jim Belknap, DVM, PhD, DACVS The Ohio State University Soft Tissue Surgery Bo Brock, DVM, DABVP (Equine) Brock Veterinary Clinic, Lamesa, Texas Surgery Noah D. Cohen, VMD, MPH, PhD, DACVIM (Internal Medicine) Texas A&M University Internal Medicine Norm G. Ducharme, DVM, MSc, DACVS Cornell University Large Animal

Compendium Equine is a refereed journal. Articles published herein have been reviewed by at least two academic experts on the respective topic and by the editor in chief.

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Compendium Equine

Raymond J. Geor, BVSc, MVSc, PhD, DACVIM Michigan State University Metabolism, Nutrition, Endocrine-Related Laminitis Katharina Lohmann, MedVet, PhD, DACVIM (Large Animal) University of Saskatchewan Large Animal Robert J. MacKay, BVSc, PhD, DACVIM (Large Animal) University of Florida Large Animal Rustin M. Moore, DVM, PhD, DACVS The Ohio State University Surgery Debra Deem Morris, DVM, MS, DACVIM East Hanover, New Jersey Internal Medicine P. O. Eric Mueller, DVM, PhD, DACVS The University of Georgia Soft Tissue and Orthopedic Surgery

Susan C. Eades, DVM, PhD, DACVIM (Large Animal) Louisiana State University Large Animal

Elizabeth M. Santschi, DVM, DACVS The Ohio State University Surgery

Earl M. Gaughan, DVM, DACVS Littleton Large Animal Clinic Littleton, Colorado Surgery

Nathaniel A. White II, DVM, MS, DACVS Virginia Polytechnic Institute and State University Surgery

Any statements, claims, or product endorsements made in Compendium Equine are solely the opinions of our authors and advertisers and do not necessarily reflect the views of the Publisher or Editorial Board.

B:8.25” T:8” S:7”

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Federal law restricts this drug to use by or on the order of a licensed veterinarian. For use in horses only. Do not use in horses intended for food.

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October 2009 Vol 4(8)

Features 353

❯❯ Todd C. Holbrook Equine practitioners should be familiar with the diagnosis and treatment of cantharidin toxicosis regardless of practice location. This article reviews the treatment goals: pain management, gastroprotection, correction of electrolyte and fluid imbalances, and prevention of further toxin absorption.

CompendiumEquine.com | Peer Reviewed | Free CE

CE

Each CE article is accredited for 3 contact hours by Auburn University College of Veterinary Medicine.

Therapeutics in Practice Treating Cantharidin Toxicosis

366 FREE

CE

❯❯ R. P. Atherton, H. C. McKenzie III, and M. O. Furr This article illustrates how disruption of normal gastrointestinal function in horses with acute colitis leads to common pathologic changes, regardless of the underlying etiology. The most common noninfectious etiologic agents are discussed to help you develop an appropriate treatment plan.

375 FREE

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Acute Colitis: Pathophysiology and Noninfectious Causes

Acute Colitis: Infectious Causes ❯❯ R. P. Atherton, H. C. McKenzie III, and M. O. Furr The key points regarding infectious etiologies of acute colitis in adult horses are highlighted to help you address each case appropriately, limit the risk of disease spread, and optimize the patient’s chance of survival.

Departments 342 CompendiumEquine.com 344 Editorial: How Did I Get Here?

350 Research Recap: Selected abstract from Veterinary Therapeutics

❯❯ Amy I. Bentz

3455

Cover image © 2009 Zuzule/Shutterstock.com

The AAEP’s Media Partnership Program is composed of an esteemed group of industry-leading media outlets dedicated to providing resources and education, through the AAEP, to veterinarians and horse owners to improve the health and welfare of horses.

340

Compendium Equine: Continuing Education for Veterinarians®

Calendar

Clinical Snapshot 346 A Severe Dermatologic Condition in a Paint Gelding ❯❯ Catherine Lamm, Melanie Breshears, Ronald D. Welsh, Grant Rezabek, and Lynn L. Rodgers

350 A Large Growth on a Quarter Horse Gelding

Reading Room 358 Natural Methods for Equine Health and Performance, 2nd ed.

360 Vault Guide to Veterinary and Animal Careers 381 Market Showcase 381 Classified Advertising 382 Product Forum

❯❯ Adam Stern

363 Weight Loss and Acute Colic in a Thoroughbred Gelding ❯❯ Holly Smith and Cyprianna Swiderski

383 The Final Diagnosis: The Grada Haus ❯❯ James N. Moore

384 Index to Advertisers

FIND THE SOLUTION TO YOUR HORSE’S NEEDS – DISCOVER YOUR PLATINUM! To find the right Platinum Performance™ nutritional solution, and to learn about the science behind the supplements call 1-800-553-2400, visit ThisIsMyPlatinum.com or speak with your equine veterinarian.

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Platinum Performance™ The Ultimate Equine Wellness and Performance Formula to support the total health of every horse

Supports • Joint function • Hoof health • Skin and coat health • Performance recovery • Digestive health • Bone and skeletal health • Healing

For preventive maintenance and to maintain soundness in horses that have suffered injuries, Dr. Beeman highly recommends a therapy program that always includes Platinum Performance Equine Wellness.

9/21/09 4:03:19 PM

WEB EXCLUSIVES

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NEWS BITS

❯❯ Dr. John Mitchell Named 2010 AAEP VP ❯❯ Australian Veterinarian Dies of Rare Virus From Horse ❯❯ Business Education, Specialty Lectures to Highlight AAEP 55th Annual Convention

❯❯ More videos to come

CONTACT US

❯❯ E-mail your questions, suggestions, comments, or letters to the editor: editor@CompendiumEquine.com

We’re for innovation.

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Only PreveNile® West Nile Virus vaccine utilizes chimera technology. Which is why PreveNile requires just one dose for primary(altrenogest) immunization – making it the perfect choice for foals and horses with unknown vaccination history as well as horses previously vaccinated with other West Nile vaccines.

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Editorial ❯❯ Amy I. Bentz, VMD, DACVIM | Veterinary Learning Systems | Yardley, Pennsylvania

How Did I Get Here?

H

ave you ever wondered, How did I get here?

The first 16 years of school seemed to pass in a blur—a rapid succession of tests, advancement through grades, graduation, and parties. Then the brakes slammed on our ascent when we entered veterinary school. The next few years were another blur of tests, clinical rotations, and externships, followed by graduation. We found our first jobs or internships, quickly realizing, when we began to see patients, that we hadn’t retained everything we needed to learn in veterinary school. But our skills improved rapidly, and we gained confidence, It can be difficult to find a learning to diagnose few minutes every day to certain diseases immeenjoying interconsider where you’ve been diately, actions with clients, and becoming an integral and where you’re headed, part of our local combut it’s worth the effort. munities. Then, suddenly, we realized that years had passed, causing us to wonder, How did I get here? What did I give up to get here?

Do you let the days go by, as in the Talking Heads song “Once in a Lifetime,” or do you take time to think about the past, present, and future?

It can be difficult to find a few minutes every day to consider where you’ve been and where you’re headed, but it’s worth the effort. The present, a

344

well-named gift, offers a daily chance to improve or change something that is nagging you because you left it behind in your effort to achieve your dream job. The present can be an opportunity to spend more time with family or friends (two or four legged), rediscover the benefits of sports and exercise, play a musical instrument, or learn a foreign language. Maybe you regret that you no longer travel, watch movies, or read for pleasure (because your books are buried under a mound of veterinary journals). Perhaps you aren’t reaching your goal of running a marathon, vacationing annually, or painting landscapes.

My grandmother used to say, “We are all given 24 hours in a day, and we decide how to spend them.” Being pulled in many directions every day can be exhausting, so we need to decide what is most important to us. My grandmother chose to spend her time caring for her family. She especially loved to iron my grandfather’s clothes (even his socks!). While I have discovered the joys of the dryer’s wrinkle-prevent cycle, I wouldn’t give up what I consider important.

Now is the time to renew yourself, rediscover some lost treasure, or begin on a new path. If possible, spend some time with children or pets to refresh your spirit. (It’s amazing how quickly they’ll play after their basic needs are met!) Their boundless energy and enthusiasm can be a tonic to weary adults who may wonder, How did I get here?

Compendium Equine: Continuing Education for Veterinarians® | October 2009 | CompendiumEquine.com

CE Calendar November 4–6 Diagnosis & Treatment of Lameness in the Horse Colorado State University Fort Collins, Colorado Phone 970-297-1273 Web www.cvmbs.colostate.edu/clinsci/ce

November 5–8 Reproductive Management and Artificial Insemination Colorado State University Equine Reproduction Lab Fort Collins, Colorado Web www.csuequine.com

November 6–8 FEEVA European Equine Meeting Royal Marine Hotel Dun Laoghaire, Co. Dublin, Ireland Phone 353 14577976 Email hq@vetireland.ie Web www.veterinaryireland.ie

Only Adequan® i.m.

November 13 Reproductive Ultrasonography in the Mare

(polysulfated glycosaminoglycan)

stimulates cartilage repair and reverses traumatic joint dysfunction

Equine Reproduction Concepts, LLC Amissville, Virginia Phone 540-937-9832 Email info@equinereproduction.com Web www.equinereproduction.com

Within 48 hours

November 13–15 FVMA 47th Annual Ocala Equine Conference

the hyaluronic acid (HA) in the synovial fluid nearly doubles after a single injection.* Recommended dose: 5 mL every 4 days for 7 treatments intramuscularly.

Ocala Hilton Ocala, Florida Phone 800-992-3862 Web www.fvma.com

November 15–17 Hagyard Equine Bluegrass Symposium

To learn about the wear-and-repair of joints go to www.adequan.com.

Or call 800-974-9247 for a free video.

Hagyard Equine Medical Institute Lexington, Kentucky Phone 859-685-3709 Email ntomlinson@hagyard.com Web www.hagyard.com

November 16 Embryo Recovery and Transfer in the Mare

Keep joints in healthy balance

Equine Reproduction Concepts, LLC Amissville, Virginia Phone 540-937-9832 Email info@equinereproduction.com Web www.equinereproduction.com

There are no known contraindications to the use of intramuscular PSGAG in horses. Studies have not been conducted to establish safety in breeding horses. WARNING: Do not use in horses intended for human consumption. Adequan® i.m. brand Polysulfated Glycosaminoglycan (PSGAG). Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Each 5 mL contains 500 mg Polysulfated Glycosaminoglycan. Brief Summary Indications: For the intramuscular treatment of non-infectious degenerative and/or traumatic joint dysfunction and associated lameness of the carpal and hock joints in horses.

LUITPOLD PHARMACEUTICALS, INC. Animal Health Division, Shirley, NY 11967.

See product package insert for full prescribing information. *Burba DJ, Collier MA, Default LE, Hanson-Painton O, Thompson HC, Holder CL: IN VIVO KINETIC STUDY ON UPTAKE AND DISTRIBUTION OF INTRAMUSCULAR POLYSULFATED GLYCOSAMINOGLYCAN IN EQUINE BODY FLUID Compiled

by Benjamin Hollis; send TRITIUM-LABELED listings COMPARTMENTS AND ARTICULAR CARTILAGE IN AN OSTEOCHONDRAL DEFECT MODEL. The Journal of Equine Veterinary Science to bhollis@vetlearn.com.

1993; 696-703. Concentrations of Adequan i.m. in the synovial fluid begin to decline after peak levels are reached at 2 hours; then remain constant from 24 hours post injection through 96 hours. © 2008 Luitpold Animal Health. Adequan® is a registered trademark of Luitpold Pharmaceuticals, Inc. AHD 85201, Iss. 2/08 CE

Compiled by Benjamin Hollis; send listings to bhollis@vetlearn.com.

Compendium Equine | October 2009

345

Clinical Snapshot Particularly intriguing or difficult cases

Oral Paste for Horses and Foals NADA 141-123, Approved by FDA Caution Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Description Chemical name: 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl) methyl]sulfinyl]-1H-benzimidazole.

Empirical formula: C17H19N3O3S. Molecular weight: 345.42. Structural formula:

Case Presentation #1 ❯❯ Catherine Lamm, DVM, DACVP* ❯❯ Melanie Breshears, DVM, DACVP ❯❯ Ronald D. Welsh, DVM ❯❯ Grant Rezabek, DVM ❯❯ Lynn L. Rodgers, DVM

H 3C

CH3 O

OCH3 H

Oklahoma State University

An 18-month-old, 340-kg (750-lb) Paint gelding presented with a chronic, severe dermatologic condition. Physical examination revealed a generalized pattern of exudative dermatitis on the dorsum, gluteal area, and shoulders (A). On closer examination, the hair was matted together in a “paint brush” or “fissured” appearance (B). Other abnormalities on physical examination included poor body condition despite an adequate appetite. The horse was depressed but responsive.

The horse was turned out in a pasture with four other horses and a mule and wore a blanket as needed. Examination of the other equids revealed that three of the other horses and the mule had similar lesions, but they were less severe and more localized on the dorsum and withers.

A

B

1. What is the differential diagnosis?

2. What diagnostic tests would you perform?

3. What are your treatment options?

SEE PAGE 348 FOR ANSWERS AND EXPLANATIONS.

*Dr. Lamm discloses that she has received an honorarium from Elsevier and research support from Intervet/Schering-Plough Animal Health.

346

OCH3

Compendium Equine: Continuing Education for Veterinarians® | October 2009

How Supplied GASTROGARD® (omeprazole) Paste for horses contains 37% w/w omeprazole and is available in an adjustable-dose syringe. Each syringe contains 2.28 g of omeprazole. Syringes are calibrated according to body weight and are available in boxes of 7 units or 72 units.

Storage Conditions Store at 68°F – 77°F (20-25°C). Excursions between 59°F – 86°F (15-30°C) are permitted.

Indications For treatment and prevention of recurrence of gastric ulcers in horses and foals 4 weeks of age and older.

Dosage Regimen For treatment of gastric ulcers, GASTROGARD Paste should be administered orally once-a-day for 4 weeks at the recommended dosage of 1.8 mg omeprazole/lb body weight (4 mg/kg). For the prevention of recurrence of gastric ulcers, continue treatment for at least an additional 4 weeks by administering GASTROGARD Paste at the recommended daily maintenance dose of 0.9 mg/lb (2 mg/kg).

Directions For Use • GASTROGARD Paste for horses is recommended for use in horses and foals 4 weeks of age and older. The contents of one syringe will dose a 1250 lb (568 kg) horse at the rate of 1.8 mg omeprazole/lb body weight (4 mg/kg). For treatment of gastric ulcers, each weight marking on the syringe plunger will deliver sufficient omeprazole to treat 250 lb (114 kg) body weight. For prevention of recurrence of gastric ulcers, each weight marking will deliver sufficient omeprazole to dose 500 lb (227 kg) body weight.

• To deliver GASTROGARD Paste at the treatment dose rate of 1.8 mg omeprazole/lb body weight (4 mg/kg), set the syringe plunger to the appropriate weight marking according to the horse’s weight in pounds.

• To deliver GASTROGARD Paste at the dose rate of 0.9 mg/lb (2 mg/kg) to prevent recurrence of ulcers, set the syringe plunger to the weight marking corresponding to half of the horse’s weight in pounds.

• To set the syringe plunger, unlock the knurled ring by rotating it 1/4 turn. Slide the knurled ring along the plunger shaft so that the side nearest the barrel is at the appropriate notch. Rotate the plunger ring 1/4 turn to lock it in place and ensure it is locked. Make sure the horse’s mouth contains no feed. Remove the cover from the tip of the syringe, and insert the syringe into the horse’s mouth at the interdental space. Depress the plunger until stopped by the knurled ring. The dose should be deposited on the back of the tongue or deep into the cheek pouch. Care should be taken to ensure that the horse consumes the complete dose. Treated animals should be observed briefly after administration to ensure that part of the dose is not lost or rejected. If any of the dose is lost, redosing is recommended.

• If, after dosing, the syringe is not completely empty, it may be reused on following days until emptied.

Replace the cap after each use.

Warning Do not use in horses intended for human consumption. Keep this and all drugs out of the reach of children. In case of ingestion, contact a physician. Physicians may contact a poison control center for advice concerning accidental ingestion.

Adverse Reactions In efficacy trials, when the drug was administered at 1.8 mg omeprazole/lb (4 mg/kg) body weight daily for 28 days and 0.9 mg omeprazole/lb (2 mg/kg) body weight daily for 30 additional days, no adverse reactions were observed.

Precautions The safety of GASTROGARD Paste has not been determined in pregnant or lactating mares.

Clinical Pharmacology Mechanism of Action: Omeprazole is a gastric acid pump inhibitor that regulates the final step in hydrogen ion production and blocks gastric acid secretion regardless of the stimulus. Omeprazole irreversibly binds to the gastric parietal cell’s H+, K+ ATPase enzyme which pumps hydrogen ions into the lumen of the stomach in exchange for potassium ions. Since omeprazole accumulates in the cell canaliculi and is irreversibly bound to the effect site, the plasma concentration at steady state is not directly related to the amount that is bound to the enzyme. The relationship between omeprazole action and plasma concentration is a function of the rate-limiting process of H+, K+ ATPase activity/turnover. Once all of the enzyme becomes bound, acid secretion resumes only after new H+, K+ ATPase is synthesized in the parietal cell (i.e., the rate of new enzyme synthesis exceeds the rate of inhibition).

Pharmacodynamics: In a study of pharmacodynamic effects using horses with gastric cannulae, secretion of gastric acid was inhibited in horses given 4 mg omeprazole/kg/day. After the expected maximum suppression of gastric acid secretion was reached (5 days), the actual secretion of gastric acid was reduced by 99%, 95% and 90% at 8, 16, and 24 hours, respectively.

Pharmacokinetics: In a pharmacokinetic study involving thirteen healthy, mixed breed horses (8 female, 5 male) receiving multiple doses of omeprazole paste (1.8 mg/lb once daily for fifteen days) in either a fed or fasted state, there was no evidence of drug accumulation in the plasma when comparing the extent of systemic exposure (AUC0-∞). When comparing the individual bioavailability data (AUC0-∞, Cmax, and Tmax measurements) across the study days, there was great inter- and intrasubject variability in the rate and extent of product absorption. Also, the extent of omeprazole absorption in horses was reduced by approximately 67% in the presence of food. This is evidenced by the observation that the mean AUC0-∞ values measured during the fifth day of omeprazole therapy when the animals were fasted for 24 hours was approximately three times greater than the AUC estimated after the first and fifteenth doses when the horses were fed hay ad libitum and sweet feed (grain) twice daily. Prandial status did not affect the rate of drug elimination. The terminal half-life estimates (N=38) ranged from approximately one-half to eight hours.

Efficacy Dose Confirmation: GASTROGARD® (omeprazole) Paste, administered to provide omeprazole at 1.8 mg/lb (4 mg/kg) daily for 28 days, effectively healed or reduced the severity of gastric ulcers in 92% of omeprazole-treated horses. In comparison, 32% of controls exhibited healed or less severe ulcers. Horses enrolled in this study were healthy animals confirmed to have gastric ulcers by gastroscopy. Subsequent daily administration of GASTROGARD Paste to provide omeprazole at 0.9 mg/lb (2 mg/kg) for 30 days prevented recurrence of gastric ulcers in 84% of treated horses, whereas ulcers recurred or became more severe in horses removed from omeprazole treatment.

Clinical Field Trials: GASTROGARD Paste administered at 1.8 mg/lb (4 mg/kg) daily for 28 days healed or reduced the severity of gastric ulcers in 99% of omeprazoletreated horses. In comparison, 32.4% of control horses had healed ulcers or ulcers which were reduced in severity. These trials included horses of various breeds and under different management conditions, and included horses in race or show training, pleasure horses, and foals as young as one month. Horses enrolled in the efficacy trials were healthy animals confirmed to have gastric ulcers by gastroscopy. In these field trials, horses readily accepted GASTROGARD Paste. There were no drug related adverse reactions. In the clinical trials, GASTROGARD Paste was used concomitantly with other therapies, which included: anthelmintics, antibiotics, non-steroidal and steroidal anti-inflammatory agents, diuretics, tranquilizers and vaccines.

Diagnostic and Management Considerations: The following clinical signs may be associated with gastric ulceration in adult horses: inappetence or decreased appetite, recurrent colic, intermittent loose stools or chronic diarrhea, poor hair coat, poor body condition, or poor performance.

Clinical signs in foals may include: bruxism (grinding of teeth), excessive salivation, colic, cranial abdominal tenderness, anorexia, diarrhea, sternal recumbency or weakness. A more accurate diagnosis of gastric ulceration in horses and foals may be made if ulcers are visualized directly by endoscopic examination of the gastric mucosa.

Gastric ulcers may recur in horses if therapy to prevent recurrence is not administered after the initial treatment is completed. Use GASTROGARD Paste at 0.9 mg omeprazole/lb body weight (2 mg/kg) for control of gastric ulcers following treatment. The safety of administration of GASTROGARD Paste for longer than 91 days has not been determined.

Maximal acid suppression occurs after three to five days of treatment with omeprazole.

Safety • GASTROGARD Paste was well tolerated in the following controlled efficacy and safety studies.

• In field trials involving 139 horses, including foals as young as one month of age, no adverse reactions attributable to omeprazole treatment were noted.

• In a placebo controlled adult horse safety study, horses received 20 mg/kg/day omeprazole (5x the recommended dose) for 90 days. No treatment related adverse effects were observed.

• In a placebo controlled tolerance study, adult horses were treated with GASTROGARD Paste at a dosage of 40 mg/kg/day (10x the recommended dose) for 21 days. No treatment related adverse effects were observed.

• A placebo controlled foal safety study evaluated the safety of omeprazole at doses of 4, 12 or 20 mg/kg (1, 3 or 5x) once daily for 91 days. Foals ranged in age from 66 to 110 days at study initiation. Gamma glutamyltransferase (GGT) levels were significantly elevated in horses treated at exaggerated doses of 20 mg/kg (5x the recommended dose). Mean stomach to body weight ratio was higher for foals in the 3x and 5x groups than for controls; however, no abnormalities of the stomach were evident on histological examination.

Reproductive Safety In a male reproductive safety study, 10 stallions received GastroGard Paste at 12 mg/kg/day (3x the recommended dose) for 70 days. No treatment related adverse effects on semen quality or breeding behavior were observed. A safety study in breeding mares has not been conducted.

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CAUTION: UTION: Federal llaw aw restricts restric icts this th drug to u use by or on the order of a licensed veterinarian. GASTROGARD is indicated for the treatment prevention recurrence of g tment and prev vention o of rec gastric ulcers in horses and foals 4 weeks and older. In efficacy trials, no adverse reactions in pregnantt or lactating mares has not been determined. DO NOT USE IN HORSES INTENDED tions were observed. obseerved. Safety Sa FOR HUMAN CONS CONSUMPTION. SUMPTI TI . KEEP THIS AND TION. AN ND ALL DRUGS OUT OF THE REACH OF CHILDREN. Mitchell RD. Prevalence of gastric ulcers in hunter/jumper and dressage horses evaluated for poor performance. Association for Equine Sports Medicine. September 2001.

Murray MJ. Endoscopic appearance of gastric lesions in foals: 94 cases (1987-1988). J Am Vet Med Assoc 1989;195(8):1135-1141.

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Clinical Snapshot Answers and Explanations Case Presentation #1

A

SEE PAGE 346 FOR CASE PRESENTATION.

1. The differential diagnosis for crusting dermatitis includes dermato-

philosis, Staphylococcus infection, ectoparasites, photosensitization, and pemphigus foliaceus.

2. Samples of scabs were removed for bacterial and fungal culture, and skin biopsy samples were obtained for histologic analysis. On histologic examination, there was mild, diffuse epidermal hyperplasia with minimal hyperkeratosis. Within the superficial dermis, there was a mild, multifocal perivascular infiltrate of lymphocytes and plasma cells. The histopathologic diagnosis was exudative dermatitis with epidermal hyperplasia. These changes were nonspecific, and an etiologic diagnosis could not be made on histologic examination.

On microscopic examination of impression smears of scabs, many branching filaments divided transversely and longitudinally in a “railroad-track” pattern (C; Diff-Quik stain; magnification, 600×).

Ectoparasites and fungal spores were not observed. The scabs were then processed, plated on blood agar, and incubated at 37°C (98.6°F) in 5% carbon dioxide. After 5 days, the colony morphology, microscopic appearance, and biochemical pattern were all typical of Dermatophilus congolensis (rain scald). No other bacteria were isolated from the fresh scabs, and mycotic cultures tested negative for dermatophytes.

3. The horse was treated with procaine penicillin IM for 7 days and reexamined 30 days later. Topical treatments were not used. There was noticeable improvement in the overall haircoat quality, with new hair growth in the fissures and areas that were previously exudative. Information on the treatments used for, and the status of, the other horses in the herd was not available. * * * The presence of a similar dermatitis on other equids from the facility suggests a possible infectious agent and concomitant management problems. D. congolensis can have various clinical presentations in horses, ranging from mild alopecia to marked crusting with underlying purulent reactions, as in this case.1,2 The organism can affect horses in winter and summer. Dermatophilosis can have a regional or diffuse anatomic distribution, with lesions on the head and the distal limbs more common in summer outbreaks.1,2 In this case, the dorsum and wither involvement suggested that bacterial or fungal dermatitis was most likely. Light microscopy of cytology or squash preparations is the most valuable diagnostic tool in the field. Observing the characteristic railroad-track morphology of the organisms on direct examination of crusts allows rapid diagnosis, as in this case.3 If full-thickness skin biopsies are attempted, it is important to include the surface crust (or submit crusts as an additional specimen) to identify the organisms in surface areas. This condition can occasionally be missed on histopathology if the surface crust is not included.

Dermatophilosis has been reported to produce significant morbidity, including weight loss and lethargy, as in this patient.1,2 Retention of moisture near the skin as a result of blanketing may have contributed

348

B

C

to the severity of skin disease in this case. One therapeutic option involves clipping (to open all matted crusts and allow complete drying of the underlying skin) and daily bathing of affected areas with povidone–iodine scrub (and then drying the areas well).1,2 Severe disease is generally associated with very moist environmental conditions and poor hygiene.

References 1. Pascoe RR, Knottenbelt DC. Bacterial diseases. In: Manual of Equine Dermatology. Philadelphia: Saunders; 1999:102-106.

2. Scott DW, Miller BH. Bacterial skin diseases. In: Equine Dermatology. Philadelphia: Saunders; 2003:234-242.

3. Biberstein EL. The skin as a microbial habitat: bacterial skin infections. In: Hirsh DC, Zee YC, eds. Veterinary Microbiology. Oxford, UK: Blackwell Science; 1999:211-212.

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Clinical Snapshot Particularly intriguing or difficult cases

A

Case Presentation #2 ❯❯ Adam Stern, DVM Oklahoma State University

A 3-year-old Quarter horse gelding with a large growth on its prepuce presented to the referral veterinarian. The ulcerated, alopecic mass had been present for an unknown duration and measured 8 × 5 × 5 cm. No other clinical abnormalities were noted on examination. The mass was debulked, and sections were submitted for histopathologic examination (A; hematoxylin–eosin stain; magnification: 20×).

1. What is your diagnosis?

2. In which areas of the body does this lesion commonly arise?

SEE PAGE 352 FOR ANSWERS AND EXPLANATIONS.

Research Recap Selected abstract from Veterinary Therapeutics

Effects of Top-Dress Formulations of Suxibuzone and Phenylbutazone on Development of Gastric Ulcers in Horses* Andrews FM, Reinemeyer CR, Longhofer SL. Vet Ther 2009;10(3):113-120.

Eighteen mature, healthy horses were divided into three groups (six per group), which received no treatment, 15 consecutive days of phenylbutazone (PBZ), or 15 consecutive days of suxibuzone (SBZ) at recommended label doses. Horses underwent endoscopy before and after the treatment period and were assigned gastric ulcer scores. Gastric ulcer number and severity scores were similar across treatment groups. These findings suggest that when administered at the recommended label dose for 15 days, neither PBZ

TO LEARN MORE

nor SBZ causes an increase in the number or severity of gastric ulcers over what would be expected with traditional stabling and intermittent feeding patterns. Also, PBZ-treated horses did not have more severe gastric ulcers than SBZ-treated horses, indicating that SBZ does not appear to offer an advantage over PBZ in preventing gastric ulcers when used at recommended label doses. However, ulcers in other regions of the gastrointestinal tract (e.g., right dorsal colon, duodenum) were not evaluated in horses in this study.

From th the he Fall 2009 issue For more Veterinary Therapeutics abstracts, visit the archives at

VeterinaryTherapeutics.com 350

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*Funding for this research was provided by Dechra Pharmaceuticals PLC, Shrewsbury, Shropshire, UK.

vetlearn_AD_1pg_PVEspecific.qxp:www_teaser_RD5

9/28/09

9:14 AM

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Clinical Snapshot Answers and Explanations Case Presentation #2 SEE PAGE 350 FOR CASE PRESENTATION.

1. Based on clinical examination and histopatho-

logic evaluation of the skin, a diagnosis of sarcoid was made. Histopathologic examination of the lesion revealed characteristic epidermal hyperplasia with prominent long rete ridges (A; arrows) and perpendicular orientation (“picketfence” appearance) of neoplastic fibroblasts at the dermoepidermal junction (B; hematoxylin– eosin stain; magnification: 100×; arrows). A definitive diagnosis cannot be made if the dermoepidermal junction is not evaluated.

The differential diagnosis of equine sarcoid includes squamous cell carcinoma, exuberant granulation tissue, habronemiasis, fibropapilloma,1 and granulomatous inflammation. The most common penile and preputial tumor is reported to be squamous cell carcinoma.2 Sarcoids are common, locally aggressive, fibroblastic cutaneous neoplasms in horses. Equine sarcoids are induced by bovine papillomavirus.3 2. Equine sarcoids are most common on the head (especially around the eyes), neck, legs, and ventral abdomen, including the prepuce. Some studies suggest that Arabians, Appaloosas, and Quarter horses are at increased risk for this neoplasm and that Standardbreds are at decreased risk.4 Reported treatments for sarcoids include surgical excision/debulking, cryotherapy, radiofrequency hyperthermia, use of intralesional cisplatin, and immunotherapy (autogenous vaccines). Recurrence rates vary depending on the treatment used; however, the prognosis for survival is good in horses with a single sarcoid.

A

B

References 1. Gardiner DW, Teifke JP, Podell BK, Kamstock DA. Fibropapilloma of the glans penis in a horse. J Vet Diagn Invest 2008;20:816-819.

2. Brinsko SP. Neoplasia of the male reproductive tract. Vet Clin North Am Equine Pract 1998;14:517-533.

3. Bogaert L, Van Poucke M, De Baere C, et al. Bovine papillomavirus load and mRNA expression, cell proliferation and p53 expression in four clinical types of equine sarcoid. J Gen Virol 2007;88:2155-2161.

4. Scott DW, Miller WH. Equine dermatology. Immune-Mediated Disorders. St. Louis: Saunders; 2003:720-731.

SHARE YOUR PICTUREPERFECT CASES IN CLINICAL SNAPSHOT

Challenge your colleagues with a particularly intriguing or difficult case in Clinical Snapshot. Submit your photo(s) along with a brief case description, at least one test question, and detailed answers to each question posed. Each published submission entitles you to an honorarium of $100.

For more details, call 800-426-9119, extension 52434, or e-mail editor@CompendiumEquine.com

352

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Therapeutics in Practice Current medical protocols for treating a variety of conditions in horses

Treating Cantharidin Toxicosis ❯❯ Todd C. Holbrook, DVM, DACVIM (Large Animal) Oklahoma State University

At a Glance Differential Diagnosis Page 353

Clinical Pathology Page 354

Common Clinical Signs Associated With Cantharidin Toxicosis Page 354

Treatment

C

antharidin toxicosis in horses is most common in the southwestern United States and is associated with the ingestion of alfalfa hay contaminated with blister beetles. While 67 species of blister beetles have been identified in Oklahoma alone, the most common species associated with toxicosis in horses are the threestriped blister beetles (Epicauta temexa and Epicauta occidentalis)1,2 (FIGURE 1). Because the geographic range of blister beetles is extensive and importation of alfalfa hay harvested from high-risk regions is possible, equine veterinarians should be familiar with the diagnosis and treatment of cantharidin toxicosis regardless of practice location. Gas chromatography and mass spectrometry of urine or gastric contents can be used to confirm the diagnosis.1

Page 354

Differential Diagnosis

Series Editor ❯❯ Debra Deem Morris, DVM, MS, DACVIM 190 State Route 10 East Hanover, NJ 07936 phone 973-599-1191 fax 973-599-1193 e-mail stretchdeem@yahoo.com

The clinical presentation of cantharidin toxicosis can vary greatly but is generally a consequence of the toxin’s (1) irritation of the gastrointestinal (GI) and renal systems and (2) action at specific molecular receptors (BOX 1). Patient variation and the dose of toxin ingested influence the clinical presentation. Multiple horses on the farm may be affected. Monensin, arsenic, and blue-green algae toxicoses may also cause sudden death in multiple horses and are plausible diagnostic possibilities.3 When clinical signs of colic predominate, the differential diagnosis will likely be influenced by the horse’s severity of pain and the presence or absence of other clinical signs, including fever and diarrhea. Because fever is very common in equine patients with can-

tharidin toxicosis, differentials such as colitis, proximal enteritis, and peritonitis are important to consider. Although general causes of colic are extensive, clinicians should primarily focus on those representative of all the clinical signs.

Horses with minimal toxin ingestion may present with mild lethargy and anorexia, while ingestion of higher doses of cantharidin can culminate in signs of hypovolemic shock and in death. Other conditions to consider in horses displaying signs of endotoxic shock include GI rupture, colitis, proximal enteritis, NSAID toxicosis, and prolonged strangulating obstructions.

Occasionally, cantharidin-intoxicated horses exhibit extreme pain that is difficult to control with analgesics and mimics a surgical intestinal lesion.

Early in the clinical course of sublethal toxicosis, horses often display ptyalism and submerge their muzzles in their water buckets to agitate the water. Frequently, this “water playing” behavior is violent, which complicates monitoring water consumption. Oral ulcerations may be present FIGURE 1

Three-striped blister beetle.

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Therapeutics in Practice Common Clinical Signs Associated With Cantharidin Toxicosis BOX 1

Physical examination findings Tachycardia Colic Fever Dysuria Lethargy and anorexia in mild cases Hypovolemic shock or death in severe cases Ptyalism and playing in water bucket Diarrhea Laboratory abnormalities Hyposthenuria (urine specific gravity: 1.004–1.007) Microscopic hematuria Hypocalcemia Hyperglycemia Hypomagnesemia

CriticalPo nt Pyrexia, dysuria, and colic are common clinical signs of cantharidin toxicosis. However, some horses may present with pyrexia, lethargy, and anorexia without signs of abdominal pain.

but, in my experience, are uncommon. Some horses display bruxism, which may be due to oral or, more likely, gastric pain because squamous epithelial ulceration is common.

During renal excretion, cantharidin induces urinary tract irritation and hemorrhage, resulting in signs of dysuria. Clinical signs can vary from pollakiuria to polyuria. Frequently, the urine is clear and dilute before fluid therapy is instituted. Hyposthenuria (urine specific gravity: 1.004 to 1.007) associated with cantharidin toxicosis is common, regardless of hydration status; in equine patients with renal failure, an isosthenuric urine specific gravity (1.008 to 1.014) is common. Hyposthenuria associated with cantharidin toxicosis is most likely due to inhibitory action of the toxin on protein phosphatase 2A receptors in the renal cortical collecting duct.

In experimental rodent models, phosphatase 2A inhibition interfered with the action of vasopressin and thus water and sodium reabsorption in the kidneys.4 Microscopic hematuria is common due to the irritant effects of cantharidin on the urinary epithelium. Geldings and stallions may exhibit paraphimosis or priapism.

Clinical Pathology The most consistent laboratory finding in equine patients with cantharidin toxicosis is hypocalce-

354

mia; however, the absence of it does not preclude this diagnosis (BOX 1). Concurrent clinical signs may include muscle fasciculations, synchronous diaphragmatic flutter, abnormal facial expression, weakness, ataxia, or a stilted gait. Other common clinicopathologic findings include hyperglycemia, hypomagnesemia, or an increased serum creatine kinase level. Rarely, cantharidin toxicosis may present with clinical and laboratory evidence of significant myopathy (creatine kinase: >200,000 IU); other causes of rhabdomyolysis should be considered in these cases. Myocardial necrosis has been documented at necropsy in some horses with fatal cantharidin toxicosis.5 While biochemical evidence of myocardial injury is common in horses with cantharidin toxicosis, myocardial dysfunction of clinical significance appears to be rare.6 Characteristic abnormalities on urinalysis include microscopic hematuria and hyposthenuria. Cytology of an abdominocentesis sample may reveal an increased total protein level and leukocyte count.7 Neutrophilic leukocytosis is common, although equine patients occasionally display neutropenia and/or left shift as well as lymphopenia. Although metabolic acidosis can occur, mixed acid–base responses are more common.

Treatment General treatment goals include elimination of toxin exposure, reduction of toxin absorption, pain management, correction of fluid and electrolyte deficits, and GI mucosal protection.

In addition, prophylactic therapy for potential complications is often warranted.

Oral Adsorbents Activated charcoal (1 to 3 g/kg) can be administered via nasogastric tube to promote GI toxin elimination. Depending on the estimated time of toxin ingestion, an oral adsorbent may be administered every 12 hours for two or three treatments. Cantharidin is lipid soluble; thus, dietary sources of oil could increase cantharidin absorption, potentiating toxicosis. Therefore, grain sources and nutritional supplements containing fat should be discontinued. Because mineral oil is poorly absorbed, some have suggested it may be useful to potentiate toxin removal.7 However, studies at my laboratory comparing the cantharidin adsorptive activity of mineral oil, activated charcoal, and di-

Compendium Equine: Continuing Education for Veterinarians® | October 2009 | CompendiumEquine.com

Treating Cantharidin Toxicosis tri-octahedral smectite suggest mineral oil is a poor choice for toxin adsorption when activated charcoal is available. If the clinician decides to administer mineral oil with other adsorbents, they should not be administered concurrently in order to avoid potential interaction. While activated charcoal was most effective at cantharidin adsorption in my laboratory’s in vitro studies, di-tri-octahedral smectite is a valid alternative if activated charcoal is not available.

Pain Management Analgesic options to treat abdominal pain associated with toxicosis include NSAIDs, α2-agonists, and narcotics. Pain control may be achieved with flunixin meglumine (1.1 mg/kg IV), but additional analgesics may be necessary. The dose and frequency of NSAIDs used should be minimized because GI mucosal lesions and hypovolemia are common with cantharidin toxicosis. Xylazine (0.3 to 0.5 mg/kg IV) and detomidine (0.01 to 0.02 mg/kg IV) are also useful for short-term analgesia. Clinically, I find butorphanol to be more useful than α2-agonists for managing severe or recurrent pain associated with cantharidin toxicosis. A loading dose of 20 μg/kg IV followed by a constant-rate infusion of 13 μg/kg/ hr IV diluted in lactated Ringer’s solution is commonly used for managing affected equine patients in my hospital. While the effects of cantharidin on nociception in horses are unknown, it was recently demonstrated that cantharidin interferes with the analgesic properties of α2-agonists in rats but has no effect on narcotic κ-agonists such as butorphanol.8

Fluid Therapy Fluid therapy is indicated to correct hypovolemia as well as electrolyte and acid–base derangements. In addition, promotion of diuresis may increase renal toxin excretion.

Appropriate fluid administration rates are initially dictated by the severity of hypovolemia and shock, if present. Monitoring the response to fluid therapy can be particularly challenging in these patients. Preexisting hyposthenuria and polyuria negate the usefulness of monitoring urine output and urine specific gravity to guide fluid administration rates. Furthermore, ptyalism and water-playing behavior can alter interpretation of mucous membrane hydration. Therefore, the clinician should critically

evaluate other clinical signs of tissue perfusion (e.g., mentation, heart rate, pulse quality, distal limb temperature, blood pressure, blood test results such as blood gas values) when estimating fluid administration rates. In severely affected equine patients, large-bore (10- to 12-gauge) catheters allow more rapid delivery of balanced electrolytes. Because ionized and total serum calcium concentrations are often low and blood pH can influence ionization, these parameters should be assessed.

Frequently, the severity of hypocalcemia in these patients requires administration of large quantities of intravenous calcium for 2 to 5 days. While the calcium deficit can be estimated mathematically, ongoing losses are common in severely affected equine patients, so it may be more practical to supplement calcium at a moderate rate and reassess serum biochemistry. To avoid cardiac toxicity, it is safer to administer calcium diluted in non–bicarbonate-containing isotonic fluids through a separate catheter at a slower rate than fluids for shock support.

Depending on the severity of hypocalcemia, I typically add 250 to 500 mL of 23% calcium borogluconate per 5-L bag of isotonic fluids administered at a maintenance rate in managing severe cantharidin toxicosis. To maintain appropriate therapy, it is often necessary to repeat serum chemistry analysis two or three times daily.

Because many of these patients are also hypomagnesemic, polyionic-concentrated solutions containing calcium and magnesium are also used. However, when serum chemistry reveals significant hypomagnesemia, supplementation with concentrated magnesium products is usually necessary. It is important to restore a normal serum magnesium concentration because parathyroid hormone secretion in response to hypocalcemia may be impeded by hypomagnesemia. I recently documented inappropriately low parathyroid hormone concentrations in a number of hypocalcemic horses with cantharidin toxicosis. In vitro studies using bovine parathyroid cell systems indicate that pharmacologic inhibition of protein phosphatase receptors impedes parathyroid hormone secretion.9

CriticalPo nt The common clinicopathologic findings of cantharidin toxicosis are hypocalcemia, hypomagnesemia, an increased creatine kinase level, and hyposthenuria.

Gastrointestinal Protectants Toxic effects of cantharidin on GI mucosa include gastric squamous epithelial ulceration, glandular mucosal irritation, and small intestinal

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355

Therapeutics in Practice FIGURE 2

Gastroscopy images.

A

B

(0.25 mg/kg IV q8h), polymyxin B (6000 U/ kg IV q8–12h) can be used for its endotoxinbinding properties during the initial treatment period (typically 1 to 3 days). When azotemia is present, the frequency of polymyxin B administration and the dose and frequency of NSAID administration should be minimized. While profound neutropenia is rarely associated with cantharidin toxicosis, systemic antimicrobial therapy is occasionally indicated in select cases with increased risk of secondary infection.

Laminitis Sheets of nonadherent desquamated epithelium adjacent to superficial ulcerations (ellipse) in the nonglandular stomach.

CriticalPo nt The treatment goals for cantharidin toxicosis are pain management, gastroprotection, correction of electrolyte and fluid imbalances, and prevention of further toxin absorption.

Raised, fluid-filled squamous epithelial “blisters” (arrows) in the nonglandular stomach.

and colonic inflammation.5 Gastroscopic findings likely depend on the time elapsed since toxin ingestion. Evidence of recent exposure includes fluid-filled squamous epithelial blisters and pale sheets of nonadherent desquamated squamous epithelium in the nonglandular portion of the stomach (FIGURE 2). After complete desquamation, coalescing bands of superficial ulceration are common in the nonglandular stomach above the margo plicatus concurrent with glandular mucosal hyperemia. I often administer sucralfate (22 mg/kg PO q6h) for GI protection. In addition, omeprazole dosed at 4 mg/kg PO q24h may be administered to reduce gastric acidity and promote healing of gastric ulcers. Long-term (>7 to 14 days) omeprazole therapy may not be indicated because clinical experience indicates that resolution of squamous epithelial superficial erosions is fairly rapid.

Goal-Specific Therapy Endotoxemia Considering the histologic severity of GI mucosal damage documented on postmortem examination, coupled with common clinical signs (i.e., mucous membrane congestion, tachycardia, tachypnea, other signs of circulatory shock) in equine patients with documented cantharidin toxicosis, endotoxemia is likely integrally involved in the pathophysiology. Therefore, rational therapy also addresses the systemic effects of endotoxin absorption.

In addition to fluid resuscitation and administration of low doses of flunixin meglumine

356

Acute laminitis is a significant complication in approximately 10% of cantharidin toxicosis cases in my hospital. Currently, there is a paucity of scientific data addressing prophylactic therapy for acute laminitis. In my hospital, deep sand bedding is commonly provided for equine patients at high risk for developing laminitis.

Aspirin therapy (20 mg/kg PO every other day) aimed at altering platelet function to prevent vascular occlusion associated with acute laminitis is often administered. When equine patients that develop acute laminitis and dorsal capsular rotation (i.e., third-phalanx rotation without distal displacement; “sinking”) are treated, biomechanical forces should be addressed by using corrective shoeing methods to control pain and stabilize the third phalanx. The most effective methods I use incorporate three basic principles: heel elevation, improved breakover, and viscoelastic weight support of the caudal sole and heel region. Analgesic options include several NSAIDs: phenylbutazone, flunixin meglumine, ketoprofen, and firocoxib. In addition, combination analgesic protocols using constant-rate infusions of intravenous lidocaine (2 mg/kg bolus followed by 50 μg/kg/min) and butorphanol have been successfully used in select cases to minimize NSAID doses.

Managing Pregnant Mares While little is known regarding the transplacental absorption of cantharidin, therapy to maintain fetal viability is an important goal in pregnant mares. In rats, cantharidin inhibits steroidogenesis; thus, it is plausible that similar effects could alter progesterone synthesis in pregnant mares with cantharidin toxicosis.10 In addition, the risk of concurrent endotoxemia is substantial. Because endotoxemia alone can lower endogenous progesterone production in

Compendium Equine: Continuing Education for Veterinarians® | October 2009 | CompendiumEquine.com

Treating Cantharidin Toxicosis early pregnancy in mares, I recommend administering altrenogest (0.044 mg/kg PO q24h).11

SHARE YOUR COMMENTS Have something to say about this topic?

Let us know:

Conclusion With early recognition and appropriate aggressive therapy, clinical experience suggests that most equine patients with cantharidin toxicosis recover.

E-MAIL editor@CompendiumEquine.com FAX 800-556-3288

References 1. Ray AC, Kyle AL, Murphy MJ, Reagor JC. Etiologic agents, incidence, and improved diagnostic methods of cantharidin toxicosis in horses. Am J Vet Res 1989;50(2):187-191.

2. Edwards WC, Edwards RM, Ogden L, Whaley M. Cantharidin content of two species of Oklahoma blister beetles associated with toxicosis in horses. Vet Hum Toxicol 1989;31(5):442-444.

3. Casteel S, Turk J. Collapse/sudden death. In: Smith BP, ed. Large Animal Internal Medicine. 3rd ed. St. Louis: Mosby; 2002:246-253.

4. Blot-Chabaud M, Coutry N, Laplace M, et al. Role of protein phosphatase in the regulation of Na-K-ATPase by vasopressin in the cortical collecting duct. J Membrane Biol 1996;153:233-239.

5 Schoeb TR, Panciera RJ. Pathology of blister beetle (Epicauta) poisoning in horses. Vet Pathol 1979;16:18-31.

6. Holbrook TC, Panciera RJ. Biochemical evidence of cardiac injury in horses with cantharidin toxicosis [abstract]. Louisville, KY: 24th Annual ACVIM Forum; 2006.

PHARM

7. Schmitz DG. Cantharidin toxicosis in horses. J Vet Intern Med 1989;3(4):208-215.

8. Moncada A, Cendan CM, Baeyens JM, Del Pozo E. Inhibitors of serine/threonine protein phosphatases antagonize the antinociception induced by agonists of alpha 2 adrenoceptors and GABAB but not kappa-opioid receptors in the tail ick test in mice. Pain 2005;114(1-2):212-220.

9. Matovcik LM, Rhee SS, Schaefer JF, et al. Inhibition of protein phosphatase 1 decreases PTH secretion from isolated dispersed parathyroid cells. Mol Cell Endocrinol 1999;154(1-2):171-177.

10. Yu CC, Chen WY, Li PS. Protein phosphatase inhibitor cantharidin inhibits steroidogenesis and steroidogenic acute regulatory protein expression in cultured rat preovulatory follicles. Life Sci 2001;70(1):57-72.

11. Daels PF, Stabenfeldt GH, Hughes JP, et al. Evaluation of progesterone deďŹ ciency as a cause of fetal death in mares with experimentally induced endotoxemia. Am J Vet Res 1991;52(2):282-288.

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Reading Room ❯❯ Reviewed by Narda G. Robinson, DO, DVM, MS, FAAMA, Colorado State University

T

wo words surfaced after I read Mary Bromiley’s second edition of her book Natural Methods for Equine Health and Performance; they were “if only.”

If only this book had stayed true to the fundamental ideals that good food, good husbandry, and good ethics produce good horses, it might have made a more meaningful difference by giving readers rock-solid information.

Title: Natural Methods for Equine Health and Performance, 2nd edition Author: Mary Bromiley, FCSP Publisher: Wiley-Blackwell Year: 2009 Pages: 238 ISBN: 978-1-4051-7929-4

TO LEARN MORE For further information about this book or to order a copy, visit

www.wiley.com/wiley-blackwell

358

If only this noted equine physiotherapist had more thoroughly researched the holistic methods she advocates before promoting them, then the section on alternative therapies might have reached the level of the physiotherapy chapters, which contain delightful and straightforward instruction integrating anatomy, biomechanics, and training considerations. If only Bromiley had done her homework, readers might have escaped the myths that plague holistic medicine, and the legitimacy of this work would have emerged untarnished. If only that were the case, but it is not.

The disclaimer at the front of the book maintains that this book should serve not as a manual but as a “background reference text.”

However, the fact that the targeted readership will likely put the book’s treatments into practice makes the situation serious when it comes to unproven or downright dangerous recommendations. Unless readers have experience sorting facts from fluff when it comes to alternative treatments, the distinction between the two becomes blurry because Bromiley offers both.

For example, the chapter titled “Feeding” begins with an insightful description of the biomechanical benefits afforded by allowing horses to consume a variety of plant matter in a head-down position. The chapter proceeds into a discussion on the science of feeding and the functions of nutrients such as water, protein, carbohydrates, fats, vitamins, and minerals.

Then the party ends. For exam-

ple, comfrey is listed nine times as a botanical (and therefore supposedly preferable) source of vitamins and minerals. Planting comfrey to provide vitamins A, C, and E, as well as calcium, copper, molybdenum, iron, phosphorus, sulfur, and zinc, may allow “natural” supplementation of these compounds in horses, but natural does not mean safe.

Bromiley overlooks the fact that comfrey most importantly contains toxic and potentially carcinogenic pyrrolizidine alkaloids.1 In 2002, the Association of American Feed Control Officials (AAFCO) cited comfrey as a “health and safety concern for animals and humans, prompting regulatory action by the United States, Canada and Germany.”

AAFCO continued, saying, “Comfrey does not meet any of the recognized criteria for use as an animal feed ingredient or animal feed.”2 More misinformation fills the acupuncture chapter. Bromiley admonishes, “In the West, you cannot practise medicine without sufficient knowledge of anatomy and disease to enable a diagnosis to be made. In the same way, no one should practise acupuncture unless they understand the basic principles of the philosophy of Chinese traditional medicine, and this includes the making of a diagnosis, mental or physical.” With this assertion, Bromiley exposes her unfamiliarity with the history of acupuncture. Bromiley fails to recognize that traditional Chinese medicine (TCM) was invented in the 1950s by Mao Tse-tung to support the Chinese Communist Revolution.3 Her lack of understanding about why and when

Compendium Equine: Continuing Education for Veterinarians® | October 2009 | CompendiumEquine.com

Reading Room TCM came about causes her to place far more faith in the primitive and folkloric methods of TCM pulse and tongue diagnoses than these arcane methods deserve. Bromiley perpetuates the illusion that TCM diagnoses offer reliable insights into the inner workings of patients, despite convincing evidence showing how widely TCM diagnoses vary between practitioners, even for the same patient. Such low reliability has led some to perhaps justifiably refer to TCM diagnoses as “worthless.”4 Furthermore, diagnosing organ dysfunction based on the look of the tongue or the feel of the pulse along specific, small sections of the carotid artery has never been validated in horses. Finally, by asserting that acupuncture involves moving invisible energy down invisible pathways, despite decades of research pointing to the neurophysiologic basis of acupuncture, Bromiley misleads her readers once again.

In summary, if only this book had stayed true to the fundamental ideals that good food,

good husbandry, and good ethics produce good horses, it might have made a more meaningful difference by giving readers rock-solid information. Instead, the audience will need to tiptoe through the patchwork of the factual and fictitious.

References 1. Hirono I, Mori H, Haga M. Carcinogenic activity of Symphytum officinale. J Natl Cancer Inst 1978;61:865. Cited in Garrett MB, Cheeke PR, Miranda CL, et al. Consumption of poisonous plants (Senecio jacobaea, Symphytum officinale, Pteridium aquilinum, Hypericum perforatum) by rats: chronic toxicity, mineral metabolism, and hepatic drug-metabolizing enzymes. Toxicol Lett 1982;10:183-188.

2. Association of American Feed Control Officials. Target ingredient announcement, AAFCO recommended enforcement event, Enforcement Strategy for Marketed Ingredients (ESMI) working group. Accessed May 2009 at www.aafco.org/Portals/0/Public/ comfrey1.pdf.

3. Taylor K. Chinese Medicine in Early Communist China, 1945-1963: A Medicine of Revolution. New York: Routledge Curzon; 2005.

4. Barrett S. Why TCM diagnosis is worthless. Accessed May 2009 at www.acuwatch.org/reports/diagnosis.shtml.

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Reading Room*

T This guide should provide a good start for both young adults making a career choice and people considering a career change.

Title: Vault Guide to Veterinary and Animal Careers Authors: Liz Stewart and the staff of Vault Publisher: Vault.com Year: 2008 Pages: 141 ISBN: 978-1-58131-548-6

*Written by Patricia L. Van Horn, a freelance writer in Long Branch, New Jersey. Reprinted from Compend Contin Educ Vet 2009;31(7):306.

TO LEARN MORE For further information about this book or to order a copy, visit vault.com.

360

HE WEB-BASED VAULT CAREER GUIDES have won high praise from a number of prominent magazines and newspapers, including The New York Times, The Washington Post, Money, Fortune, and Forbes. Designed to answer some basic questions (e.g., “What are the career opportunities in working with animals?” “Is this the right job for you?”), this guide covers everything “from soup to nuts”—what jobs are available, how to get each one, and what each will be like.

Although the emphasis is firmly along with nuggets of advice. on the practical, the book begins by The book concludes with a chapproviding a brief background about ter on “alternative job opportunities” animals in society. It then moves on related to animals, such as educato industry trends, from zoos to eco- tion, sales, advocacy, law, and media. tourism and from scientific research A useful appendix lists professional to farming. organizations, schools, and helpful The core of the book features Web sites. sections on the wide range of jobs This guide should provide a good available to those who wish to make start for both young adults making a a career of working with animals, career choice and people considering including veterinary medicine (doc- a career change. The approach takes tors, technicians, and assistants), a lighter tone—for example, listing breeding, farming/ranching, animal “uppers” and “downers” for each job— control, zoo and wildlife management, but never diverges from the pragmatic. research, service industries, and cor- The language is clear and intelligent porate and government positions. Follow ing this is a SHARE YOUR COMMENTS chapter on employers for Have a question or comment about this each of these categories. book review? Let us know: The discussion then shifts E-MAIL editor@CompendiumEquine.com to how to get the job in question—education and FAX 800-556-3288 train ing, breaking into WEB CompendiumEquine.com the field at various levels (including starting a business), constructing a resume, and does not “dumb down” the suband interviewing. The next chap- ject matter. And as befits the pubter takes the reader on the job, lisher’s strong Web connections, the addressing lifestyle and financial book recognizes the role today’s issues and providing “career snap- information technology plays in the shots” comprising interviews of job market. For those who love anipeople who hold the job in ques- mals, this book should help to detertion. Interviewees offer details on mine whether their passion might duties, hours, and pros and cons, translate into practical work.

Compendium Equine: Continuing Education for Veterinarians® | October 2009 | CompendiumEquine.com

STATEMENT OF OWNERSHIP, MANAGEMENT AND CIRCULATION (Required by 39 U.S.C. 3685) 1. Title of Publication: Compendium Equine: Continuing Education for Veterinarians, 2. Publication Number: 1559-5811, 3. Date of Filing: October 1, 2009, 4. Frequency of Issue: Monthly except February, August, and December, 5. Number of Issues Published Annually: 9, 6. Annual Subscription Price: $79, 7. Complete Mailing Address of Known Office of Publication: Veterinary Learning Systems, 780 Township Line Road, Yardley, Bucks County, PA 19067, Contact Person: Christine Polcino, Telephone: 267-685-2419, 8. Complete Mailing Address of Headquarters or General Business Office of the Publisher: Veterinary Learning Systems, 780 Township Line Road, Yardley, PA 19067, 9. Full Names and Complete Mailing Addresses of Publisher, Editor, and Managing Editor—Publisher: Derrick Kraemer, Veterinary Learning Systems, 780 Township Line Road, Yardley, PA 19067; Editor: Tracey Giannouris, 780 Township Line Road, Yardley, PA 19067; Managing Editor: Kirk McKay, 780 Township Line Road, Yardley, PA 19067, 10. Owner: Veterinary Learning Systems/MediMedia USA, 780 Township Line Road, Yardley, PA 19067, 11.

Known Bondholders, Mortgagees, and Other Security Holders Owning or Holding 1 Percent or More of Total Amount of Bonds, Mortgages or Other Securities: None, 12. Tax Status: Has Not Changed During Preceding 12 Months, 13. Publication Title: Compendium Equine: Continuing Education for Veterinarians, 14. Issue Date for Circulation Data Below: July/August 2009, 15. Extent and Nature of Circulation— 15a.Total Number of Copies (Net Press Run) - Average Number Copies Each Issue During Preceding 12 Months: 17,820, Actual Number Copies of Single Issue Published Nearest to Filing Date: 17,930, 15b(1). Paid/Requested Outside-County Mail Subscriptions Stated on Form 3541 - Average Number Copies Each Issue During Preceding 12 Months: 78, Actual Number Copies of Single Issue Published Near-

est to Filing Date: 78, 15b(3). Sales Through Dealers and Carriers, Street Vendors, Counter Sales, and other Non-USPS Paid Distribution - Average No. Copies Each Issue During Preceding 12 Months: 0, Actual No. Copies of Single Issue Published Nearest to Filing Date: 0, 15c. Total Paid and/or Requested Circulation - Average No. Copies Each Issue During Preceding 12 Months: 78, Actual No. Copies of Single Issue Published Nearest to Filing Date: 78, 15d(1). Free Distribution by Mail (Samples, Complimentary, and Other Free): Outside-County as Stated on Form 3541 - Average No. Copies Each Issue During Preceding 12 Months: 16,160, Actual No. Copies of Single Issue Published Nearest to Filing Date: 16,600, 15d(4). Free or Nominal Rate Distribution Outside the Mail - Average No. Copies Each Issue During Preceding 12 Months: 0, Actual No, Copies of Single Issue Published Nearest To Filing Date: 0, 15e. Total Free Distribution Outside the Mail - Average No. Copies Each Issue During Preceding 12 Months: 16,160, Actual No. Copies of Single Issue Published Nearest to Filing Date: 16,600, 15f. Total Distribution - Average No. Copies Each Issue During Preceding 12 Months: 16,238, Actual No. Copies of Single Issue Published Nearest to Filing Date: 16,678, 15g. Copies not Distributed - Average No. Copies Each Issue During Preceding 12 Months: 1,582, Actual No. Copies of Single Issue Published Nearest to Filing Date: 1,252, 15h. Total - Average No. Copies Each Issue During Preceding 12 Months: 17,820, Actual No. Copies of Single Issue Published Nearest to Filing Date: 17,930, 15i. Percent Paid - Average No. Copies Each Issue During Preceding 12 Months: 1%, Actual No. Copies of Single Issue Published Nearest to Filing Date: 1%, 16. This Statement of Ownership will be printed in the October 2009 issue of this publication. 17. I certify that the statements made by me above are correct and complete: Derrick Kraemer, Publisher.

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Clinical Snapshot Particularly intriguing or difficult cases

Case Presentation #3 ❯❯ Holly Smith, DVM, JD Interstate Equine Services Goldsby, Oklahoma

❯❯ Cyprianna Swiderski, DVM, MS, DACVIM College of Veterinary Medicine, Mississippi State University

An 11-year-old Thoroughbred gelding with a history of chronic weight loss had acute colic for several hours and was referred to an equine hospital. The gelding had no history of colic, and its behavior included rolling, followed by periods of depression. On physical examination, the patient was tachycardic (68 bpm) and tachypneic (48 breaths/min). A nasogastric tube was inserted, and 12 L of reflux was obtained. Several minutes later, the reflux fluid became dark red, indicating frank hemorrhage. The horse’s oral mucous membranes became pale, and its packed cell volume dropped from 33% to 22% over a period of 30 minutes; therefore, a whole blood transfusion was performed using a compatible donor. Gastroscopy revealed two round, dark masses in the glandular portion of the stomach near the margo plicatus (A and B).

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www.equinehyperbarics.com 363

Clinical Snapshot Answers and Explanations Case Presentation #3 SEE PAGE 363 FOR CASE PRESENTATION.

1. Equine gastric ulcer syndrome (EGUS)

with hemorrhage is the most likely diagnosis. Other possibilities include trauma and neoplasia. The clinical picture of this horse was not severe enough to consider complete gastric perforation. However, the possibility of incomplete gastric perforation, in which the serosal layer of the stomach remains intact, was considered.

Trauma to the esophagus or stomach, perhaps due to esophageal or gastric stricture that could restrict passage of a nasogastric tube, was considered unlikely because of the ease with which the tube was inserted into the stomach. This finding, coupled with the history of weight loss, raised the suspicion of trauma to a preexisting gastric ulcer. Biopsies of the lesion margin were indicated in the diagnostic workup of this case and performed to rule out neoplasia. Biopsy results obtained 24 hours after admission revealed intercellular edema and mild neutrophilic infiltrates consistent with deep gastric ulceration and acute trauma. Follow-up gastroscopy is warranted 2 to 3 weeks after initiation of gastric ulcer treatment; failure to respond to therapy should prompt further diagnostics.

2. EGUS occurs in the glandular and squamous (nonglandular) parts of the stomach when the protective mechanisms of each region are overwhelmed by gastric acid exposure; however, lesions are more common in the squamous stomach. Numerous peptides, including gastrin, histamine, and acetylcholine, affect acid secretion by parietal cells. Risk factors leading to an increase in gastric pH and, therefore, to potential ulcer formation include feed deprivation, training, stress, and a high-carbohydrate diet.

The squamous epithelium has few protective mechanisms, mak-

364

A

B

ing ulceration more common in this region than in the glandular portion of the stomach. In the squamous portion of the stomach, intercellular tight junctions and secreted bicarbonate ions protect the epithelium from acid damage.

Epidermal growth factor may play a protective role in the squamous mucosa by inhibiting gastric acid secretion and stimulating mucosal regeneration.1 A surface barrier composed of mucins and/or an osmiophilic phospholipid layer has been identified on the squamous mucosa; this surface barrier is thought to act as a physical barrier to acid.1 High mucosal blood flow is considered an important protective factor in the glandular stomach because it allows rapid turnover of epithelial cells and maximizes bicarbonate buffering and mucus secretion.

Mucosal prostaglandin E2, which promotes mucosal blood flow, potentiates these effects, preserves the structural integrity of tight junctions, and suppresses gastric acid secretion. As in the nonglandular stomach, epidermal growth factor from saliva also has a protective effect on glandular mucosa by facilitating proliferation of gastric mucosa cells.

3. Once a diagnosis of gastric ulceration is confirmed, the major treatment goals are to facilitate healing by

reducing acid production, providing mechanical protection, and increasing epithelialization. Pain associated with gastric ulceration makes inappetence a major concern. Reluctance to eat worsens ulcers by reducing the buffering capacity provided by ingesta. This is especially problematic in horses because gastric acid secretion is continuous, even during periods of anorexia.

Medications commonly used in treating equine gastric ulcers include H2-receptor antagonists, antacids, mucosal protectants, proton pump inhibitors, and prostaglandin analogues. Of these agents, only the proton pump inhibitor omeprazole (Gastrogard, Merial) is approved by the FDA for treating EGUS. Ranitidine (6.6 mg/kg PO q8h), an H2-receptor antagonist, may also be used in horses to improve discomfort by suppressing gastric acid secretion. H2-receptor antagonists reduce gastric acid secretion by inhibiting H2-receptor–mediated acid secretion by gastric parietal cells. Several H2receptor antagonists, including ranitidine (1.5 mg/kg IV q8h), can be administered intravenously in patients that cannot tolerate oral medications.

Clinical signs may be temporarily relieved by administering an antacid or mucosal protectant such as a magnesium hydroxide/aluminum

Compendium Equine: Continuing Education for Veterinarians® | October 2009 | CompendiumEquine.com

Clinical Snapshot

hydroxide combination product. Single doses of 30 g of aluminum hydroxide with 15 g of magnesium hydroxide (400 mL of Maalox Extra Strength [Novartis]) administered via a nasogastric tube can increase gastric pH to >4.0 (a critical threshold for ulcer healing) for at least 2 hours.2 Accordingly, amelioration of pain by this antacid therapy should increase the index of suspicion for gastric ulceration. Although antacids provide symptomatic relief, the need to administer them every 2 hours minimizes their practical usefulness.

Sucralfate (10 to 25 mg/kg PO q8h), a sulfated polysaccharide complexed with aluminum hydroxide ions, is commonly administered as an adjunctive therapy for managing gastric ulcers and often temporarily relieves clinical signs. In an acidic environment, sucralfate becomes viscous and partially dissociates into sucrose octasulfate and aluminum hydroxide. Although aluminum hydroxide provides some buffering capacity, the cytoprotective mechanisms of sucralfate are multifactorial. In the stomach, sucralfate binds to the surface of an ulcer, forming an insoluble barrier that protects the ulcer and prevents further tissue disruption by acid, bile, or pepsin. Sucralfate also limits pepsin activation and increases prostaglandin synthesis, leading to improved mucosal integrity and enhanced epithelial regeneration. In addition, sucralfate appears to have trophic effects on the ulcerated mucosa, possibly by binding growth factors and concentrating them at the ulcer site.

Misoprostol is a prostaglandin E1 analogue that inhibits acid secretion by decreasing cAMP generation triggered by histamine stimulation

of parietal cells. In addition, misoprostol protects the gastric mucosa by increasing production of gastric mucus and bicarbonate. As a prostaglandin analogue, misoprostol can cause abdominal pain and diarrhea and is therefore commonly limited to treatment of severe gastric ulceration or ulceration of the right dorsal colon in horses.

Misoprostol can induce abortion in mares and in women handling the drug. Therefore, misoprostol is contraindicated in pregnant mares, and owners administering misoprostol should wear gloves and be cautioned regarding its adverse effects.

Omeprazole is an FDA-approved therapeutic agent for treating EGUS. The drug reduces basal and stimulated gastric acid secretion by inhibiting parietal cell H+,K+-ATPase.3,4 Administered at 4 mg/kg PO q24h, omeprazole increases gastric pH to >4 for 21 to 24 hours, which has been shown to be necessary for optimal healing of equine gastric ulcers.4 Moderation of gastric pH may require 2 to 4 days of therapy, during which the patient may remain painful. Therefore, ranitidine and/or sucralfate is sometimes coadministered with omeprazole for 3 days.

4. NSAIDs such as flunixin meglumine and phenylbutazone are commonly used for managing pain and in flammation in horses. Adverse effects of NSAIDs, including right dorsal colitis, and renal toxicosis, are well characterized in horses.

NSAID use should be judicious to avoid complications.

Stress and high-concentrate diets are considered to be important predisposing factors for EGUS, accounting for its high prevalence in racehorses and other performance horses fed high-concentrate diets. The find-

ing that gastric ulcers can be induced by withholding feed illustrates the importance of a horse’s need for continuous access to roughage for its ability to buffer excess stomach acid and prevent the formation or progression of ulcers.

In addition to a blood transfusion and volume expansion with intravenous crystalloid fluid therapy at presentation, the horse in this case received oral omeprazole (4 mg/ kg q24h), ranitidine (7 mg/kg q8h), sucralfate (25 mg/kg q8h), and misoprostol (4 μg/kg q12h) for 30 days.

Management changes to minimize prolonged periods of extreme gastric acidity, including free-choice forage and frequent (four times per day) small meals of an extruded concentrate, were recommended and were instituted by the owner.

The owner also increased the duration of daily turnout and removed the gelding from training during convalescence. Reexamination of the ulcers by gastroscopy after 30 days of ulcer therapy showed that severe glandular ulcerations had resolved but mild hyperkeratosis remained along the margo plicatus in the region of the lesser curvature.

To prevent recurrence of the condition, a treatment regimen of a maintenance dose of omeprazole (2 mg/ kg q24h) along with the previously described feeding changes was recommended to the owner.

References 1. Bell RJW, Mogg TD, Kingston JK. Equine gastric ulcer syndrome in adult horses: a review. N Z Vet J 2007;55(1):1-12.

2. Clark CK, Merritt AM, Burrow JA, Steible CK. Effect of aluminum hydroxide/magnesium hydroxide antacid and bismuth subsalicylate on gastric pH in horses.

JAVMA 1996;208(10):1687-1691.

3. Wallmark B. Omeprazole: mode of action and effect on acid secretion in animals. Scand J Gastroenterol Suppl 1989;166:12-18.

4. Daurio CP, Holste JE, Andrews FM, et al. Effect of omeprazole paste on gastric acid secretion in horses.

Equine Vet J Suppl 1999;29:59-62.

CompendiumEquine.com | October 2009 | Compendium Equine: Continuing Education for Veterinarians®

365

3 CE CREDITS

CE Article 1

Acute Colitis: Pathophysiology and Noninfectious Causes* ❯❯ R. P. Atherton, BVSc, MSc, DACVIM, MRCVS Lingfield Equine Vets, Chester Lodge, Felbridge, Surrey, United Kingdom

❯❯ H. C. McKenzie III, DVM, MS, DACVIM ❯❯ M. O. Furr, DVM, PhD, DACVIM Marion duPont Scott Equine Medical Center, VirginiaMaryland Regional College of Veterinary Medicine

At a Glance Normal Physiology Page 367

Pathophysiology Page 369

Parasite-Associated Colitis Page 370

Antimicrobial-Associated Colitis Page 371

NSAID Toxicosis Page 371

Cantharidin Toxicosis Page 371

Plant Toxicosis Page 372

Carbohydrate Overload Page 372

*A companion article on infectious causes begins on page 375.

366

Abstract: Acute colitis is a common and potentially devastating condition in adult horses. While supportive care is critical in treating acute colitis, timely provision of appropriate therapies can maximize the chance for recovery. This article reviews the normal physiology of the equine large intestine and illustrates how disruption of normal gastrointestinal function in acute colitis leads to common pathologic changes, regardless of the underlying etiology. The most common noninfectious etiologic agents of acute colitis in horses are discussed to permit development of an appropriate treatment plan.

A

cute colitis is a debilitating condition that can affect horses and ponies of any breed, age, or sex.1 By definition, colitis is associated with inflammation of the colonic mucosa that invariably leads to development of diarrhea; however, diarrhea may not be present on initial examination. The degree of colonic inflammation can be profound, leading to severe losses of fluid and electrolytes and possible permanent intestinal injury. Despite aggressive treatment, the clinical status of an affected equine patient can deteriorate rapidly, and the mortality rate can be high.2 While the literature regarding the fatality rate of acute colitis in horses is limited, fatality rates of 32% to 60% for salmonellosis and 15% to 35% for Potomac horse fever have been reported.3,4 Determining the underlying etiology of acute colitis can be challenging. Few causes of acute colitis in adult horses have been documented compared with causes in other animals and humans. In one report, a definitive diagnosis was reached in only approximately 35% of cases of acute equine

colitis.5 In addition, identification of a specific etiologic diagnosis may be complicated by multiple potential pathogens. Regardless of the cause, similar clinical signs (i.e., diarrhea, abdominal pain, pyrexia, cardio-

TO LEARN MORE

Consultant’s l ’ C Corner: H How D Do I Diagnose and Manage Right Dorsal Colitis? (Winter 2006) Related content on

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FREE

Acute Colitis: Pathophysiology and Noninfectious Causes CE vascular failure) or even sudden death may be seen, representing derangement in the normal physiologic process of the large intestine (e.g., the colon and cecum). This article describes the normal physiology of the equine large intestine and the fundamental pathophysiology associated with acute colitis. It also reviews the common noninfectious etiologic agents of acute equine colitis (TABLE 1).

Most Common Noninfectious and Parasitic Diagnostic Differentials for Acute Colitis in Adult Horses TABLE 1

Category Parasitic Toxic

Normal Physiology The equine large intestine includes the cecum, large colon, transverse colon, small colon, and rectum. The cecum has an average length of 1 m and a fluid capacity of 33 L, while the large colon is 3 to 4 m in length and has a capacity of as much as 130 L. The small colon is narrow and has a small total capacity, but it can be up to 4 m in length.6 The large intestine is the principal site of digestion and water balance in horses; on a normal daily basis, it secretes and recovers a volume of fluid approximately equal to the total extracellular fluid volume of the horse—approximately 100 L/day.7 Up to 75% of the energy requirement of horses is obtained through carbohydrate metabolism by microbial fermentation in the cecum and colon; specifically, the most important products are volatile fatty acids (VFAs; e.g., acetic, propionic, and butyric acids). A stable luminal environment is required for efficient functioning of the cecum and colon; therefore, luminal pH should be tightly maintained between 6.8 and 7.2, and colonic and cecal luminal osmolality should be kept at approximately 300 mOsm.8 Passage of fluid and digesta through the cecum and large colon is relatively slow to allow adequate time for microbial digestion, fermentation, and absorption of the products of digestion. Fluid can take up to 50 hours to move through the large colon, and digesta can take 2 to 3 days, with times varying according to the type of digesta.9 The cecum and colon have three phases of motor activity: mixing, retention, and retropulsion of ingesta.10 Motility in the cecum consists of mixing contractions in which the haustra alternately contract and relax. In addition, every few minutes, a strong, mass movement–type contraction forces some of the cecal contents through the cecocolic orifice into the colon.11 Within the colon, mixing and haustral contractions efficiently blend the ingesta and expose it to the mucosal surface

Miscellaneous

Differential

Etiologic Factor

Strongylosis

Strongylus vulgaris

Cyathostomiasis

Small strongyles

NSAID use

Excessive dose or prolonged therapy

Antimicrobial use

Increased risk with oral antimicrobials and β lactams

Cantharidin

Blister beetle ingestion

Plants

Different toxic agents of variable potency

Carbohydrate overload

Excessive consumption of soluble carbohydrates

for absorption of water, electrolytes, and VFAs produced by bacterial fermentation.9 Under normal physiologic conditions, water moves into or out of the intestine until the osmotic pressure of the intestinal contents equals that of plasma.9 The absorption of water depends on absorption of nutrients (e.g., sugars, amino acids) and ions. Absorption is mostly transcellular because tight junctions form intercellular contacts that regulate solute movement through the paracellular pathway (FIGURE 1).

The ion shifts of primary importance in the equine colon include net absorption of sodium FIGURE 1

Epithelial cells

Apical side Protein complex/tight junction

Web of transmembrane tight junctions

Paracellular space

Basolateral side Tight junctions seal the spaces between adjacent epithelial cells, preventing free movement of water and electrolytes between the GI lumen and the interstitium.

CompendiumEquine.com | October 2009 | Compendium Equine: Continuing Education for Veterinarians®

367

FREE CE Acute Colitis: Pathophysiology and Noninfectious Causes

FIGURE 2

3Na+ Active transport ATP +35 mV

Blood

2K+ Epithelial cells

1

CO2

2

H2CO3– Na+

GI lumen

+O– +H

Cl–

H+

HCO3–

HCO3– CO2

H+ VFAs

Transport mechanisms in the equine colon. (1) The Na+-K+-ATPase pump uses ATP; by its action, Na+ is pumped out of GI cells via primary active transport.

The Na+-H+ and Cl–-HCO3– pumps use energy from other sources and are examples of secondary active transport. Tight junctions between the cells and the electrochemical gradient prevent free paracellular movement of ions. (2) After ingestion of feed by the horse, the volatile fatty acid (VFA) concentration increases in the colonic lumen. CO2 is absorbed across the cells, hydrates to form carbonic acid, and then dissociates into bicarbonate and hydrogen ions in the colonic lumen.

Concurrently, Na+-H+ exchange is inhibited by the high level of VFAs; therefore, the HCO3– concentration increases. Once the VFAs have been absorbed, the Na+-H+ exchange activity increases again and the H+ enters the lumen to buffer the HCO3–.

and chloride ions and net secretion of bicarbonate ions (FIGURE 2). The transport mechanisms for these ions involve passive and active forces. Passive forces include the intrinsic permeability of intestinal epithelial cells, osmotic pressure gradient exerted by the contents of the intestinal lumen, electrical potential difference across intestinal epithelial cells, concentration gradient of solutes across intestinal epithelial cells, and pH of luminal contents.8 Active transport mechanisms include primary and secondary processes. Primary active transport involves movement of an ion against its electrochemical gradient using energy. In the equine colon, sodium is actively transported by the sodium– potassium–adenosinetriphosphatase (Na+-K+ATPase) pump present in the basolateral cell membranes of the colonic epithelial cells. This pump actively moves three sodium ions out of the cell into the interstitium while moving two potassium ions into the cell. This creates an electrochemical gradient of approximately 35 mV across the mucosal surface of colonic epithelial cells, which facilitates movement of

368

sodium from the colonic lumen into epithelial cells. The secondary active transport systems use “free energy” derived from passive diffusion of one ion down its electrochemical gradient to transport another ion against its electrochemical gradient. Sodium–hydrogen ion and chloride–bicarbonate exchange systems of this type have been identified in the mucosal surface of equine colonic epithelial cells.8 Digestion in the colon is primarily by bacterial fermentation (normal large intestinal flora in horses is primarily composed of anaerobes and streptococci) in conjunction with cellulolytic bacteria (in the equine colon), which appear to be similar to those found in the rumen of ruminants.12 Fermentation of soluble and insoluble carbohydrates yields VFAs, carbon dioxide, methane, and lactate. VFAs, the primary energy source in horses, are passively absorbed through the mucosa of the colon and cecum into the blood and are transported to the liver to be metabolized. Their absorption is tightly regulated by the luminal environment of the large intestine. At a normal pH of large intestinal contents (e.g., 6.8 to 7.2), 99% of VFAs are ionized (dissociated).8 However, this form is poorly absorbed compared with the un-ionized (undissociated) form.13 VFAs become un-ionized by transfer of hydrogen ions, primarily from carbon dioxide. Carbon dioxide diffuses into cells of the cecal and colon walls, hydrates to form carbonic acid, and then dissociates into bicarbonate and hydrogen ions.8 In addition, bicarbonate ions are actively secreted via transporters in the basolateral membrane of colonic cells into the colonic lumen and then accumulate in luminal fluid.

High luminal concentrations of VFAs inhibit the Na+-H+ exchange. However, as VFAs become un-ionized and are absorbed, this pump activity increases, and hydrogen ions enter the colonic and cecal lumens and buffer the increased level of bicarbonate ions.8 Hydrogen ions are also used to transport sodium ions into the cell, which drives water absorption (FIGURE 2).

Tight regulation of the resident gastrointestinal (GI) microbial population is important, as normal flora protects the host from pathogenic bacteria through colonization resistance (i.e., in competing for space and nutrients, the normal flora inhibits colonization and proliferation of pathogenic bacteria).14 Normal flora competes with potentially pathogenic organisms for attachment sites on the epithelial surface of the mucosa.

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Acute Colitis: Pathophysiology and Noninfectious Causes CE VFAs produced by normal flora further block bacterial attachment by inhibiting growth of pathogenic bacteria. Normal flora also produces bacteriocins that inhibit growth of potential pathogens.14 Any disturbance in the normal flora impairs these defense mechanisms, increasing susceptibility of the intestine to colonization by pathogenic organisms.

Specific host defenses that further preclude the growth of pathogenic bacteria include gastric pH, GI motility, the mucosal barrier, and mucosal immunity.

Pathophysiology The pathophysiologic mechanisms of acute colitis can be divided into inflammation, abnormal passive and active secretion, and decreased transit time. The inflammatory process is complex: it has many different components. The equine large intestine is poised to mount an inflammatory response to antigenic stimuli through numerous lymphoid follicles and mast cells distributed throughout the mucosae of the cecum and colon and by neutrophils and macrophages that are normally within the colonic mucosa and submucosa.15 Unfortunately, the process by which inflammatory cells attack foreign antigens is not always specific or well regulated and may lead to secondary damage to host tissues.

Neutrophil, eosinophil, mast cell, and mononuclear cellular responses and inflammatory mediators such as prostaglandins and leukotrienes can all result in cellular and tissue damage. In a recent equine colitis study, the prostaglandin E2 (PGE2) level increased with time after a castor oil challenge and correlated with granulocyte infiltration.16 However, neutrophil influx is not definitively detrimental because neutrophil-associated PGE2 and interleukin (IL)-1β have been shown to promote tissue repair and healing.17 Proinflammatory cytokine production also plays a significant role in the development of inflammation within the colonic mucosa. For example, murine acute colitis models have demonstrated increased levels of IL-1α/β, IL-6, IL-18, and granulocyte colony-stimulating factor within the colonic mucosa.18 Bradykinin and histamine are released by neutrophils and mast cells during inflammation, and studies have shown that they increase secretion and impair absorption by the colonic mucosa.19 The

production and liberation of oxygen free radicals, which are directly cytotoxic, lead to further injury of the colonic mucosal epithelium.

Oxygen free radicals may potentiate activity of proteolytic enzymes released by phagocytic cells during the inflammatory process.

They can also inhibit antiproteases, which are naturally within colonic mucosa and prevent protease-induced cellular damage. When tissue injury becomes severe, mucosal epithelial cells are lost, leading to erosion and ulceration.19 Overall, disruption of colonic mucosa leads to a reduction in epithelial surface area, loss of absorptive cells, and failure of tight junctions, with a net result of increased fecal water secondary to impaired reabsorption and increased passive secretion. Recent studies that tried to correlate cytokine concentrations and macroscopic colonic lesions found an increase in interferon-γ and IL-6 related to the presence of necrosis of the colonic mucosa.20 Passive fluid loss from the vasculature is minimized in healthy horses because the capillary endothelium is relatively impermeable to macromolecules (e.g., albumin). These macromolecules produce tissue oncotic pressure that resists movement of fluid into the interstitium.

However, in acute colitis, the endothelium is often damaged, resulting in increased capillary permeability to macromolecules and loss of albumin from the capillaries to the interstitium.21 Agents that may increase capillary permeability in equine colitis include endotoxins, enterotoxins, oxygen free radicals, histamine, and prostaglandins.15 Normally, small fluctuations in the driving forces for fluid movement do not cause interstitial edema because of factors that resist expansion of the matrix (edema safety factors).22 However, in acute colitis, diminished oncotic pressure across the capillary wall leads to decreased fluid retention by the remaining protein within the capillary lumen. As a result, fluid leaks from the circulation into the interstitium and hypoproteinemia worsens. Therefore, development of interstitial edema becomes a self-perpetuating process.23 Movement of albumin into the interstitium promotes this fluid shift because tissue oncotic pressure is maintained by albumin despite increasing fluid accumulation. This results in progressive tissue edema and plasma protein loss into the interstitium and, eventually, the intestinal lumen.

CriticalPo nt The large intestine performs microbial digestion of fibrous feed material through a tightly regulated and physiologically complex environment.

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FIGURE 3

2 Cl– Na+

Blood

+

*OnBNNBUPSZ NFEJBUPST UIBU JODSFBTF JOUSBDFMMVMBS D".1

K+

t 1(&1 BOE 1(&2

Epithelial cell +

Na

Cl–

–

+ cAMP

t 7BTPBDUJWF JOUFTUJOBM QFQUJEF 7*1

t $BMDJVN

(* MVNFO

H+

H2O

Increased cAMP due to endogenous agents such as PGE1, PGE2, VIP, and calcium leads to increased CI— secretion. Inflammatory mediators increase intracellular cAMP concentration, which leads to opening of chloride channels. Chloride secretion increases, and water follows passively. Luminal sodium increases due to inhibition of the Na+-H+ pump by an increased cAMP level. Increased cAMP also increases K+ transport out of intestinal cells, increasing intracellular chloride levels.

CriticalPo nt A definitive diagnosis may be elusive in cases of acute colitis; therefore, understanding the pathophysiology of colitis can facilitate the development of an appropriate treatment plan.

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In many horses with colitis, there is also active secretion of solutes and water by inflamed colonic mucosa.24 As discussed earlier, the fluid and electrolyte transport processes in colonic epithelial cells are tightly governed by many different processes. While many of these processes have not been studied in detail in horses, research performed in many species indicates that the single most important secretory event leading to increased fecal water (diarrhea) and electrolyte loss is probably increased chloride ion secretion, which is primarily mediated by increased intracellular cAMP.22 An increase in chloride secretion directly increases water secretion because water passively follows chloride ions. Additionally, a compensatory increase in water reabsorption is prevented by the inhibitory effect of increased intracellular cAMP on the Na+-H+ pump, leading to decreased sodium reabsorption and associated reabsorption of water. Increased cAMP also increases potassium transport out of the intestinal cells via a basolateral potassium pump, thereby increasing intracellular chloride levels and further enhancing chloride secretion down the concentration gradient. Endogenous agents that can increase intracellular cAMP include PGE1, PGE2, calcium, and vasoactive intestinal peptide8 (FIGURE 3).

Intestinal motor function is vital to normal digestion and absorption. Fluid will not traverse the intestinal tract unless propelled by contractile activity.9 Propulsive and segmental activity of muscle layers within the intestinal tract mixes food with intestinal secretions, alters the surface area of intestine exposed to luminal contents, and regulates the rate of intestinal transit and contact time during which mucosal absorption occurs. Abnormal smooth muscle activity has been shown to occur in acute colitis and may be a response of the bowel to irritation and/or increased intraluminal volume.25 When inflammation occurs, smooth muscle contractions decrease due to endogenous myosin phosphatase inhibitor CPI-17 suppression and altered activity of muscarinic receptors and ion channels.26 Typically, abnormal motility involves an increased rate of transit due to decreased segmental contractions that normally impede intestinal flow.27 This increased rate of transit leads to decreased contact time for fluid absorption, resulting in increased fecal water content and increased frequency of defecation (i.e., diarrhea). In addition, there is reduced clearance of bacteria from the large intestine, which may contribute to the virulence of potentially pathogenic organisms.28

Parasite-Associated Colitis While parasite-associated colitis is most often clinically associated with chronic diarrhea, sudden-onset diarrhea has been reported in horses.29 Cyathostomes (small strongyles) and large strongyles are important equine parasites associated with acute colitis.30,31 In cyathostome infestation, injury to colonic mucosa is thought to be related to simultaneous maturation and release of hypobiotic cyathostome larvae from the cecal and colonic mucosae.

This phenomenon is seasonal; therefore, the disease is expected to occur only in late winter and early spring, although the stimulus for larval emergence is not clear.29 Emergence of encysted larvae causes mucosal injury, ulceration, and inflammation, all of which may be responsible for development of clinical disease.14 Alternatively, diarrhea associated with large strongyle infestation (most importantly, infestation with Strongylus vulgaris) is typically acute and occurs within several days of infestation. Fourth-stage larvae migrate from

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Acute Colitis: Pathophysiology and Noninfectious Causes CE the lumen through the mucosa and submucosa into arterioles of the intestine, causing mural edema, hemorrhage, and infiltration of the wall by inflammatory cells.32 Increased secretion and decreased absorption of fluid and electrolytes stimulated by inflammatory mediators such as prostaglandins and histamine may also play a role in colitis induced by large strongyles.

Antimicrobial-Associated Colitis Antimicrobial administration can be associated with colitis in equine patients.2 The resulting condition can be very severe, and horses with antimicrobial-associated diarrhea are reported to be 4.5 times less likely to survive than those with diarrhea from other causes.2 Antimicrobials may precipitate diarrhea by disrupting GI flora and depleting the normal population of obligate anaerobes and streptococci.

This interferes with colonization resistance.33 Additionally, normal anaerobic bacteria in the GI tract produce short-chain fatty acids and other metabolites toxic to facultative anaerobic bacteria. Loss of normal anaerobic flora leads to depletion of these short-chain fatty acids, which are also important for carbohydrate fermentation and absorption of sodium and water by colonic mucosa.12 Antimicrobials that are highly concentrated within the GI lumen exert a more profound effect on GI flora than other antimicrobials.

Antimicrobials that are administered orally or excreted in bile that undergo enterohepatic circulation (e.g., oxytetracycline, doxycycline) are of greatest concern.34 Broad-spectrum antimicrobials such as tetracyclines and β-lactams are most commonly associated with colitis in humans; in horses, trimethoprim–sulfamethoxazole, macrolides, cephalosporins, and tetracyclines have been reported to cause colitis.34–38

shown to inhibit epithelial cell migration and mucosal restitution.40 NSAID toxicosis manifests as two clinical syndromes called generalized NSAID toxicosis and right dorsal colitis.

In patients with the generalized form, mucosal ulceration occurs throughout the GI tract, and oral and gastric lesions are very common; in patients with right dorsal colitis, the ulceration is focal and severe. Why the ulceration is expressed only in the right dorsal colon in some horses is unknown, but both clinical syndromes are often associated with the development of diarrhea.

The detrimental effects of NSAIDs are typically dose dependent; in most reported cases of NSAID toxicosis, affected horses were receiving higher-than-recommended doses, often over many days.41 The toxic dose of phenylbutazone in healthy horses has been reported to be 8 to 10 mg/kg/day for several days; doses of 15 mg/ kg/day or higher, when given on multiple days, were found to be lethal, with death occurring as early as day 4 of treatment.42 Flunixin meglumine appears to be less toxic than phenylbutazone, but foals given 1.1 mg/kg/day for 30 days developed signs of toxicosis.43 In another study, flunixin meglumine dosed at 6.6 mg/kg/ day IV for 5 days was necessary to produce clinical signs of toxicosis in a group of neonatal foals.44 Combining nonsteroidal therapies (commonly called stacking) increases the potential for toxicosis. Significant GI ulceration and protein-losing enteropathy were reported when a combination of phenylbutazone and flunixin meglumine was administered to 13 adult horses, even though each drug was administered at the published, and seemingly appropriate, dose for 5 days.45 Although NSAID toxicosis is usually dose dependent, there are reports of idiosyncratic toxicoses in which horses that received recommended doses of phenylbutazone developed right dorsal colitis.46

CriticalPo nt The use of some common drugs (e.g., NSAIDs, antimicrobials) can precipitate acute colitis.

NSAID Toxicosis NSAIDs are well recognized as having potential toxic effects on the equine GI tract; these effects may lead to diarrhea. PGE2 and PGI2 are critical for maintaining normal mucosal blood flow within the GI tract; therefore, inactivation of COX enzymes by NSAIDs can lead to decreased prostaglandin production, which, in turn, impairs mucosal blood flow, leading to mucosal injury and inflammation.39 In addition, the administration of COX inhibitors has been

Cantharidin Toxicosis Cantharidin is the toxic principle found in beetles of the genus Epicauta, which are commonly known as blister beetles. These beetles feed on alfalfa flowers and can be incorporated into hay if the alfalfa is cut and processed simultaneously, as by crimping. Horses then ingest beetles with the hay. Cantharidin is a potent GI irritant, causing acantholysis and vesicle formation when applied topically.47 This

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FREE CE Acute Colitis: Pathophysiology and Noninfectious Causes

TABLE 2

Plants That May Induce Acute Colitis in Adult Horses

Plant

Toxic Agent

Clinical Signs

Acorn/oak (Quercus spp)

Tannins

Acute onset of severe abdominal pain, rectal straining, hemorrhagic diarrhea, marked intestinal borborygmi

Oleander (Nerium oleander)

Cardiac glycosides

Sudden death; cardiac irregularities; profuse, watery, bloody diarrhea

Buttercup (Ranunculus spp)

Ranunculin (protoanemonin)

Oral irritation, salivation, abdominal pain, diarrhea that may be bloody

Nightshades (Solanum spp)

Solanine

Salivation, abdominal pain, increased borborygmi and diarrhea

Rhododendron, azaleas (Rhododendron spp)

Grayanotoxins (glycosides)

Salivation, diarrhea, abdominal pain, tremors, cardiac abnormalities, death

Pokeweed (Phytolacca americana)

Phytolaccatoxin, phytolaccigenin

GI irritation (colic, diarrhea that may be bloody), anemia (rare), death

Castor bean (Ricinus communis)

Ricin

Abdominal pain, diarrhea, depression, incoordination, profuse sweating, increased body temperature

CriticalPo nt While many of these processes have not been studied in detail in horses, research performed in many species indicates that the single most important secretory event leading to increased fecal water (diarrhea) and electrolyte loss is probably increased chloride ion secretion, which is primarily mediated by increased intracellular cAMP.

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leads to severe ulceration and inflammation of the GI mucosa throughout the GI tract, resulting in severe diarrhea, which is often fatal. For more on cantharidin toxicosis, see the article beginning on page 353.

Plant Toxicosis Plant toxicosis appears to be an uncommon cause of acute colitis, although this may be related to the difficulty of determining that plant toxicosis is the cause of the diarrhea. A wide range of toxic plants can induce diarrhea in horses48 (TABLE 2). Signs can vary from chronic to peracute and life-threatening, depending on the toxic agent and dose ingested. Most plant toxicoses are associated with signs beyond simple diarrhea—oral ulceration and cardiac complications are common.

the buffering capacity of the large intestine is overwhelmed. This profoundly acidic condition results in death of the resident microbial flora. In turn, lactic acid increases the osmotic load within the large intestine, leading to development of secretory diarrhea. The acidity also results in necrosis, erosion, and inflammation of large intestinal mucosa, exacerbating water, protein, and electrolyte loss into the intestinal lumen. In addition, bacterial endotoxins and other toxic principles are absorbed across the inflamed large intestinal mucosa. Subsequently, inflammatory cytokines are produced at a level sufficient to induce systemic inflammation, which may lead to systemic disease, such as endotoxemia and laminitis.

Conclusion Carbohydrate Overload Overconsumption of soluble carbohydrates overwhelms the absorptive capabilities of the small intestine, causing a high percentage of soluble carbohydrates to enter the large intestine. The subsequent pathogenesis for acute colitis primarily involves toxic effects on microbial flora in the large intestine.14 An increased amount of soluble carbohydrates reaches the cecum and colon, resulting in rapid fermentation by gram-positive, lactic acid–producing bacteria and a sudden increase in organic acid production. The intestinal pH decreases rapidly, and

Knowledge of the pathophysiology and etiology of acute colitis allows clinicians to formulate rational diagnostic and therapeutic plans, maximizing the potential for positive outcomes in these challenging cases. While treatment is fundamentally supportive in nature, therapies targeting the appropriate etiologic agent may aid in decreasing mucosal inflammation and injury, thereby diminishing the severity of diarrhea and the systemic inflammatory response. Supportive treatment modalities directed toward the underlying pathophysiologic mechanisms may be beneficial even if the etiology is unknown.

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References 1. Baverud V, Gustafsson A, Franklin A, et al. Clostridium difficile: prevalence in horses and environment, and antimicrobial susceptibility. Equine Vet J 2003;35:465-471.

2. Cohen ND, Woods AM. Characteristics and risk factors for failure of horses with acute diarrhea to survive: 122 cases (1990-1996).

JAVMA 1999;214:382-390.

3. Mulville P. Equine monocytic ehrlichiosis (Potomac horse fever): a review. Equine Vet J 1991;23:400-404.

4. Carter JD, Hird DW, Farver TB, et al. Salmonellosis in hospitalized horses: seasonality and case fatality rates. JAVMA 1986; 188:163-167.

5. Mair TS, de Westerlaken LV, Cripps PJ, et al. Diarrhoea in adult horses: a survey of clinical cases and an assessment of some prognostic indices. Vet Rec 1990;126:479-481.

6. Jones SL, Snyder JR, Spier SJ. Physiology of the large intestine. In: Reed SM, Bayly WM, eds. Equine Internal Medicine. Philadelphia: WB Saunders; 1998:651-655.

7. Hines MT. Diarrhea. In: Reed SM, Bayly WM, Sellon DC, eds. Equine Internal Medicine. 2nd ed. Philadelphia: Saunders; 2004:156-163.

8. Murray MJ. Digestive physiology of the large intestine in adult horses. Part 1. Mechanisms of fluid, ions, and volatile fatty acid transport. Compend Contin Educ Pract Vet 1988;10:1204-1211.

9. Argenzio RA, Lowe JE, Pickard DW, et al. Digesta passage and water exchange in the equine large intestine. Am J Physiol 1974;226:1035-1042.

10. Ross MW, Donawick WJ, Sellers AF, et al. Normal motility of the cecum and right ventral colon in ponies. Am J Vet Res 1986;47:1756-1762.

11. Ross MW, Rutkowski JA, Cullen KK. Myoelectric activity of the cecum and right ventral colon in female ponies. Am J Vet Res 1989;50:374-379.

12. Argenzio RA. Physiology of diarrhea—large intestine. JAVMA 1978;173:667-672.

13. Vernay M. Colonic absorption of inorganic ions and volatile fatty acids in the rabbit. Comp Biochem Physiol A 1986;83:775-784.

14. Jones SL. Inflammatory diseases of the gastrointestinal tract causing diarrhea. In: Reed SM, Bayly WM, Sellon DC, eds. Equine Internal Medicine. 2nd ed. Philadelphia: Saunders; 2004:884-913.

15. Murray MJ. Digestive physiology of the large intestine in adult horses. Part II. Pathophysiology of colitis. Compend Contin Educ Pract Vet 1988;10:1309-1317.

16. McConnico RS, Argenzio RA, Roberts MC. Prostaglandin E2 and reactive oxygen metabolite damage in the cecum in a pony model of acute colitis. Can J Vet Res 2002;66:50-54.

17. Blikslager AT, Moeser AJ, Gookin JL, et al. Restoration of barrier function in injured intestinal mucosa. Physiol Rev 2007;87:545-564.

18. Melgar S, Karlsson A, Michaelsson E. Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL/6 but not in BALB/c mice: correlation between symptoms and inflammation.

Am J Physiol Gastrointest Liver Physiol 2005;288:G1328-G1338.

19. Jones SL, Spier SJ. Pathophysiology of colonic inflammation and diarrhea. In: Reed S, Bailey SR, eds. Equine Internal Medicine.

Philadelphia: WB Saunders; 1998:660-663.

20. Bertevello PL, Logullo AF, Nonogaki S, et al. Immunohistochemical assessment of mucosal cytokine profile in acetic acid experimental colitis. Clinics 2005;60:277-286.

21. Roberts MC, Clarke LL, Johnson CM. Castor-oil induced diarrhoea in ponies: a model for acute colitis. Equine Vet J Suppl 1989:60-67.

22. Field M, Rao MC, Chang EB. Intestinal electrolyte transport and diarrheal disease (1). N Engl J Med 1989;321:800-806.

23. Granger DN, Barrowman JA. Microcirculation of the alimentary tract I. Physiology of transcapillary fluid and solute exchange. Gastroenterology 1983;84:846-868.

24. Argenzio RA. Neuro-immune pathobiology of infectious enteric disease. Adv Exp Med Biol 1997;412:21-29.

25. Myers BS, Dempsey DT, Yasar S, et al. Acute experimental distal colitis alters colonic transit in rats. J Surg Res 1997;69:107-112.

26. Ohama T, Hori M, Momotani E, et al. Intestinal inflammation down-regulates smooth muscle CPI-17 through induction of TNFalpha and causes motility disorders. Am J Physiol Gastrointest Liv-

er Physiol 2007;292:G1429-G1438.

27. Myers BS, Martin JS, Dempsey DT, et al. Acute experimental colitis decreases colonic circular smooth muscle contractility in rats. Am J Physiol 1997;273:G928-G936.

28. O’Loughlin EV, Scott RB, Gall DG. Pathophysiology of infectious diarrhea: changes in intestinal structure and function. J Pediatr Gastroenterol Nutr 1991;12:5-20.

29. Larsen J. Acute colitis in adult horses. A review with emphasis on aetiology and pathogenesis. Vet Q 1997;19:72-80.

30. Thamsborg SM, Leifsson PS, Grondahl C, et al. Impact of mixed strongyle infections in foals after one month on pasture. Equine Vet J 1998;30:240-245.

31. Lyons ET, Drudge JH, Tolliver SC. Larval cyathostomiasis. Vet Clin North Am Equine Pract 2000;16:501-513.

32. Slocombe JO. Pathogenesis of helminths in equines. Vet Parasitol 1985;18:139-153.

33. Borriello SP. The influence of the normal flora on Clostridium difficile colonisation of the gut. Ann Med 1990;22:61-67.

34. Ensink JM, Klein WR, Barneveld A, et al. Side effects of oral antimicrobial agents in the horse: a comparison of pivampicillin and trimethoprim/sulphadiazine. Vet Rec 1996;138:253-256.

35. Papich MG. Antimicrobial therapy for gastrointestinal diseases.

Vet Clin North Am Equine Pract 2003;19:645-663, vi.

36. Keir AA, Stampfli HR, Crawford J. Outbreak of acute colitis on a horse farm associated with tetracycline-contaminated sweet feed.

Can Vet J 1999;40:718-720.

37. Stratton-Phelps M, Wilson WD, Gardner IA. Risk of adverse effects in pneumonic foals treated with erythromycin versus other antibiotics: 143 cases (1986-1996). JAVMA 2000;217:68-73.

38. Oliver OE, Stämpfli H. Acute diarrhea in the adult horse: case example and review. Vet Clin North Am Equine Pract 2006;22(1):73-84.

39. Semble EL, Wu WC. Prostaglandins in the gut and their relationship to non-steroidal anti-inflammatory drugs. Baillieres Clin Rheumatol 1989;3:247-269.

40. Campbell NB, Jones SL, Blikslager AT. The effects of cyclo-oxygenase inhibitors on bile-injured and normal equine colon. Equine Vet J 2002;34:493-498.

41. Collins LG, Tyler DE. Experimentally induced phenylbutazone toxicosis in ponies: description of the syndrome and its prevention with synthetic prostaglandin E2. Am J Vet Res 1985;46:1605-1615.

42. MacKay RJ, French TW, Nguyen HT, et al. Effects of large doses of phenylbutazone administration to horses. Am J Vet Res 1983;44:774-780.

43. Traub-Dargatz JL, Bertone JJ, Gould DH, et al. Chronic flunixin meglumine therapy in foals. Am J Vet Res 1988;49:7-12.

44. Carrick JB, Papich MG, Middleton DM, et al. Clinical and pathological effects of flunixin meglumine administration to neonatal foals. Can J Vet Res 1989;53:195-201.

45. Reed SK, Messer NT, Tessman RK, et al. Effects of phenylbutazone alone or in combination with flunixin meglumine on blood protein concentrations in horses. Am J Vet Res 2006;67:398-402.

46. Cohen ND, Carter GK, Mealey RH, et al. Medical management of right dorsal colitis in 5 horses: a retrospective study (1987-1993). J Vet Intern Med 1995;9:272-276.

47. Schmitz DG. Cantharidin toxicosis in horses. J Vet Intern Med 1989;3:208-215.

48. Murphy MJ. Field Guide to Common Animal Poisons. Ames: Iowa State University Press; 1996.

Watch for an upcoming article on treating acute colitis.

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1. Which of the following has not been associated with acute diarrhea in adult horses? a. S. vulgaris b. Dictyocaulus viviparus c. cantharidin d. flunixin meglumine e. ceftiofur sodium 2. Which of the following crosses the colon wall by primary active transport? a. sodium b. water c. potassium d. bicarbonate e. VFAs 3. Which of the following regarding the normal physiology of the equine colon is false? a. The tight junctions in the colon are impermeable to water and electrolytes, aiding in the creation and maintenance of an electrochemical gradient across the mucosa. b. Water passively follows the absorption or secretion of ions. c. The Na+-K+-ATPase transporter is present in the luminal membrane of the colon. d. Secondary active transport of ions requires ATP, which is commonly provided by the Na+-K+-ATPase pump. e. The pH of the luminal contents of the colon is 6.8 to 7.2.

4. Which statement regarding the Na+-K+ATPase pump is true? a. It pumps three sodium ions out of the cell for every two potassium ions pumped in. b. It creates an electrochemical gradient of approximately 100 mV across the colonic epithelial cells. c. It moves ions passively. d. It is a membrane transporter specific to the large intestine.

374

e. Na+-K+-ATPase stands for sodium-potassium-adenosine monophosphatase.

5. Which of the following pathophysiologic mechanisms is not common in equine patients with acute colitis? a. abnormal secretion b. decreased absorption c. inflammation d. fibrosis e. abnormal motility 6. Which statement regarding the physiology of colonic epithelial cells is false? a. cAMP is an important component in chloride ion transport. b. A high level of cAMP increases the transport of potassium out of the cells. c. Vasoactive peptide, PGE1, and PGE2 can increase cAMP. d. An increase in cAMP blocks the basolateral chloride channels in the cells. e. Luminal sodium increases when cAMP increases due to blockade of the Na+-H+ pump.

7. Which statement regarding parasitic diarrhea is true? a. Cyathostomes rarely cause parasiteassociated diarrhea. b. Stage L5 cyathostomes can encyst. c. S. vulgaris larvae do not migrate. d. Parasite-associated diarrhea is due to inflammation, increased secretion, and ulceration within the large colon. e. Parasite-associated diarrhea always causes death within a couple of days.

8. Which statement regarding NSAID administration is false? a. NSAID toxicosis is typically associated with prolonged administration or abnormally increased doses of NSAIDs. b. NSAID-associated acute colitis is due to GI ulceration. c. NSAID administration leads to a

decrease in prostaglandin production, which, in turn, impairs mucosal blood flow and leads to mucosal injury and inflammation. d. The administration of phenylbutazone and flunixin meglumine concurrently is associated with a lower risk of toxicosis than the administration of two consecutive doses of phenylbutazone. e. NSAIDs are often used to treat acute colitis because of their antiinflammatory and antiendotoxic effects.

9. Which statement regarding carbohydrate overload is false? a. As the increased amount of soluble carbohydrates reaches the large intestine, the pH increases rapidly, becoming alkalotic. b. The resident microbial flora is killed by rapid fermentation of soluble carbohydrates in the cecum and the large colon. c. The change in pH results in necrosis, erosion, and inflammation of the intestinal mucosa. d. Endotoxemia and laminitis are possible sequelae to carbohydrate overload. e. The death of the patient from carbohydrate overload is usually secondary to laminitis or endotoxemia.

10. Which statement regarding noninfectious agents that are potentially toxic to the equine colon is false? a. Cantharidin can cause ulceration of the entire GI tract when ingested. b. NSAIDs most often cause ulceration of the right ventral colon. c. Oral antimicrobial administration is more likely to lead to acute colitis than is intravenous antimicrobial administration. d. If alfalfa hay is crimped, the risk of cantharidin toxicosis increases. e. Cephalosporins have been associated with antimicrobial-induced colitis.

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CE Article 2

3 CE CREDITS

Acute Colitis: Infectious Causes* ❯❯ R. P. Atherton, BVSc, MSc, DACVIM, MRCVS Lingfield Equine Vets, Chester Lodge, Felbridge, Surrey, United Kingdom

❯❯ H. C. McKenzie III, DVM, MS, DACVIM ❯❯ M. O. Furr, DVM, PhD, DACVIM Marion duPont Scott Equine Medical Center, VirginiaMaryland Regional College of Veterinary Medicine

At a Glance Salmonella spp Page 375

Clostridium difficile Page 376

Clostridium perfringens Page 377

Potomac Horse Fever Page 378

*A companion article on pathophysiology and noninfectious causes begins on page 366.

Abstract: Infectious causes of acute colitis are of considerable concern to horse owners. Acute infectious colitis not only is a severe, potentially fatal disease but also carries a risk of disease outbreak in a group of horses. Understanding commonly recognized infectious etiologies can help clinicians address each case appropriately, limit the risk of disease spread, and optimize the patient’s chance of survival. This article highlights the key points regarding infectious etiologies of acute colitis in adult horses (i.e., older than 12 months).

A

cute colitis is well recognized in horses and ponies and can be fatal even if aggressive therapy is administered. This article addresses the common infectious causes of acute colitis (TABLE 1). Acute colitis most often affects individual horses, but associated infectious agents may cause disease outbreaks (e.g., salmonellosis, intestinal clostridiosis) and may carry a zoonotic risk.1,2 Prompt recognition of acute colitis by the attending clinician and an appropriate isolation protocol are critical for limiting the risk to unaffected horses and humans. As with many diseases, the fecal–oral route is the main way in which horses or humans contract infectious enteric diseases.

Unlike many noninfectious etiologies for which diagnostic testing is limited, tests such as whole blood polymerase chain reaction (PCR) testing and tests for fecal samples (e.g., bacterial culture, PCR testing, toxin ELISAs) are available to detect common infectious causes of acute colitis. However, while these tests may help determine a definitive diagnosis, results are often not obtained in a timely manner, and treatment should not be delayed pending results.

Salmonella spp Salmonellosis is the most frequently diag-

nosed infectious cause of diarrhea in horses.3 Salmonella spp are gram-negative facultatively anaerobic bacteria. Numerous serotypes can infect horses, with those in groups B (including Salmonella ser Typhimurium and Salmonella ser Agona) and C2 (Salmonella newport) appearing to be associated with disease more often than those in other groups.3 Four clinical syndromes of Salmonella infection are commonly described and have been reproduced experimentally in horses:

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TABLE 1

Infectious Causes of Acute Colitis in Horses

Differential

Etiologic Factor Involved

Salmonellosis

Large number of Salmonella serotypes

Intestinal clostridiosis

Clostridium difficile Clostridium perfringens

Potomac horse fever

Neorickettsia risticii

Inapparent infections; latent or active carrier states Acute diarrhea Depression, fever, anorexia, and neutropenia without diarrhea or colic Septicemia with or without diarrhea

CriticalPo nt Understanding infectious causes of acute colitis is important for preventing disease spread in the equine population.

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In acute cases of Salmonella enterocolitis, the first step in the pathogenesis involves disruption of the host’s defenses, including gastric pH, gastrointestinal (GI) motility, colonization resistance, and mucosal immunity.

This permits colonization of the distal small intestine and the colon by Salmonella bacteria attaching to and entering mucosal epithelial cells in the ileum, cecum, and proximal large colon.3 The common portal of entry into intestinal cells is the brush border, but bacteria can also penetrate via tight junctions.3 Bacteria enter the lamina propria, are phagocytosed by mucosa-associated macrophages, and then multiply intracellularly and initiate local inflammation. Leukocytes are recruited and activated, resulting in production of prostaglandins, leukotrienes, reactive oxygen metabolites, and histamine.4 Damaged mucosal epithelial cells and activated macrophages produce proinflammatory cytokines (e.g., interleukin-1, tumor necrosis factor α), which further up-regulate the local inflammatory response. When these cytokines reach the circulation, they initiate a systemic inflammatory response (e.g., fever, tachycardia, tachypnea). While Salmonella organisms that have crossed the mucosal barrier may enter the bloodstream (either directly or via the lymphatic system), in most cases, bacteria do not disseminate beyond intestinal mucosa and mesenteric lymph nodes.3 Additional pathogenic mechanisms demonstrated by Salmonella bacteria include toxin production and increased colonic secretion.

Salmonella-associated cytotoxin inhibits protein synthesis in mucosal cells, causing mor-

phologic damage and altered permeability.4 Virulent salmonellae also produce enterotoxin similar to the heat-labile toxin produced by Escherichia coli.4 This enterotoxin increases secretion of chloride and water by colonic mucosal cells via a prostaglandinmediated increase in intracellular cAMP.5 Due to severe tissue injury and the ensuing inflammatory response, acute enterocolitis caused

by Salmonella organisms is characterized by severe fibrinonecrotic typhlocolitis with interstitial edema and variable degrees of intramural vascular thrombosis that may progress to infarction.6 Recovery of normal large intestinal function typically takes at least 5 to 7 days, but mucosal injury may be severe enough that normal function will not return and diarrhea will become chronic.

Clostridium difficile Clostridium difficile is an obligate anaerobic, spore-forming, gram-positive rod that is environmentally ubiquitous in spore form. It was first identified in human neonatal feces in 1935.

C. difficile organisms are among the first bacteria acquired after a foal’s birth, representing a component of the normal GI flora of foals and adult horses.7,8 C. difficile has been reported to cause acute enterocolitis in humans and horses and is now recognized as the primary cause of nosocomial and antimicrobial-associated diarrhea and colitis in humans.9 While salmonellosis is reportedly the most common infectious cause of acute colitis in horses, the incidence of C. difficile–associated colitis appears to be increasing. The involvement of C. difficile in equine enteric disease was first established in 1987, when the organism was associated with diarrhea in 27 of 43 foals in an enterocolitis outbreak.10 Disruption of GI flora by stress, antimicrobial therapy, or other factors allows overgrowth of C. difficile; subsequent release of toxins leads to acute diarrhea.

C. difficile is considered the most common enteric pathogen in hospitalized humans.11 C. difficile infection is usually associated with antimicrobial therapy; in humans, the risk of contracting the disease increases as antimicrobial treatment continues.12 Additional risk factors for C. difficile infection in horses include severe underlying disease, presence of a nasogastric tube, dietary change, starvation, transportation, and administration of antiulcer medication.7

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Acute Colitis: Infectious Causes CE Hospitalization and antimicrobial therapy are also risk factors for development of C. difficile colitis in horses; in one study, 18 of 43 (42%) horses that developed acute colitis during antimicrobial treatment cultured positive for C. difficile.8 In horses, a wide variety of antimicrobials have been associated with C. difficile diarrhea; however, orally administered antimicrobials, or antimicrobials recycled via the enterohepatic system, have been shown to be most likely to increase the number of clostridial colony-forming units in equine feces.9 A horse can be infected by vegetative cells or spores of C. difficile from other infected horses, a contaminated environment, or humans. C. difficile spores are not easily destroyed in the environment; they can survive in inoculated feces for at least 4 years.7 Another possible route of infection is proliferation of C. difficile spores in the GI tracts of subclinical carriers.7 If normal GI flora is disrupted (e.g., by a dietary change, antimicrobial administration, or GI surgery), the risk of establishment and proliferation of C. difficile increases. Following ingestion, C. difficile spores survive the low pH of the stomach and upper small intestine, germinate in the terminal ileum, and multiply in the colonic lumen. In the absence of competition from indigenous microflora, the number of bacteria increases, producing toxins that damage intestinal tissue.11 Assessment of C. difficile involvement is further complicated because not all strains of C. difficile can cause disease.7 Pathogenic strains produce at least five different toxins, of which toxins A and B have been studied in most detail.13 Adenosine diphosphate–ribosyltransferase (binary toxin) was recognized recently, but its role in disease has not been determined.14 Toxin A, an enterotoxin, is thought to have the most significant role regarding induction of fluid secretion, inflammation, and characteristic alterations in intestinal morphology. Toxin A also weakens the tight junctions between epithelial cells lining the colon, helping toxin B enter epithelial cells.4 Toxin A induces neutrophil influx into intestinal tissue as well as mast cell degranulation and secretion of prostaglandins, histamine, inflammatory cytokines, and 5-hydroxytryptamine by activated leukocytes, leading to vasodilatory and secretory responses in enterocytes.8 Toxin B has profound cytotoxic effects in vitro and

is more than 1000 times more cytotoxic than toxin A but has demonstrated minimal damage to intact intestinal mucosa.15 However, a toxin A–negative, toxin B–positive strain of C. difficile has been implicated in human colitis, suggesting that toxin B may also be pathogenic.15

Clostridium perfringens Clostridium perfringens is similar to C. difficile in its appearance, physiologic requirements, and environmental behavior. It is considered a normal inhabitant of the GI tract of horses, with positive identification on fecal culture in 12% to 22% of healthy adult horses and 90% of 3-day-old foals.16 Dietary factors such as antimicrobial treatment and stressful stimuli can induce intestinal dysbacteriosis characterized by an overgrowth of C. perfringens. However, unlike C. difficile, which has been recognized as a cause of colitis in horses with no predisposing factors, there is debate as to whether C. perfringens can be a primary cause of colitis in adult horses.3,13 Experimental administration of C. perfringens enterotoxin to ponies has been documented to cause clinical signs of colitis, suggesting that this bacterium can be pathogenic in adult horses.17 Certainly, if C. perfringens overgrowth occurs, large quantities of enterotoxin could be produced, possibly having pathogenic effects on the colon and leading to clinical signs of colitis.18 The many genetically distinct strains of C. perfringens have variable virulence and produce one or more exotoxins. The pattern of exotoxin production is used to classify C. perfringens into five biotypes: A, B, C, D, and E. C. perfringens type A is the most common clostridial isolate from healthy horses of all ages but is also the most common isolate from adults and foals with diarrhea; therefore, the organism may cause disease if overgrowth occurs. Type C is the most commonly reported clostridial enteric pathogen in foals in North America.4 The identification of C. perfringens types B, D, or E from clinical cases of colitis is rare.

All five C. perfringens biotypes produce α-toxin, which hydrolyzes lecithin complexes in the membranes of capillary endothelium and other cells as well as in mitochondria. This results in impaired glucose uptake and energy production as well as in activation of arachi-

CriticalPo nt Salmonellosis is the most common infectious cause of acute colitis in horses, but the incidence of Clostridium difficile–associated colitis appears to be increasing.

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FREE CE Acute Colitis: Infectious Causes

donic acid metabolism and protein kinase C signaling pathways in enterocytes, resulting in cellular damage and potential cell death.4 Oral administration of α-toxin in humans was associated with increased secretion by small intestinal mucosal cells; however, no evidence of cytotoxicity was seen.19 The pathogenic significance of α-toxin in horses remains poorly understood.

Virulent strains of C. perfringens type A and, to a lesser extent, type C typically produce an enterotoxin. This cytotoxin enters cell membranes and forms pores that alter cellular permeability to water and macromolecules, ultimately leading to cellular necrosis.20 β2-Toxin is also of likely pathogenic significance. It is thought to be a pore-forming toxin similar to enterotoxin. It has been documented to be produced by a type of C. perfringens found in horses with colitis, suggesting a pathogenic role of β2-toxin in the etiology of C. perfringens–associated colitis.21

CriticalPo nt Salmonellosis and clostridiosis can occur year-round, whereas Potomac horse fever and many noninfectious causes of acute colitis are considered to be seasonal.

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Potomac Horse Fever Potomac horse fever (equine monocytic ehrlichiosis) is caused by the obligate intracellular rickettsial organism Neorickettsia risticii.

This organism’s role in Potomac horse fever was established more than 20 years ago when inoculation of a horse with blood from an infected horse led to development of clinical signs.22 However, until reliable PCR tests were developed and recent studies completed, the life cycle remained undefined. Studies have now shown that the causative rickettsial organisms live within trematodes. These trematodes are ingested by freshwater operculate snails and aquatic insects that become intermediate hosts.23,24 Bats and birds may be definitive hosts of the helminth vector and a natural reservoir of N. risticii, but the definitive host of N. risticii remains a subject of debate.25 However, the mechanism of transmission of N. risticii to horses has been clarified by challenge studies. Ingestion of numerous intermediate hosts, namely aquatic insects, including stoneflies, mayflies, and aquatic water snails, leads to development of clinical signs consistent with Potomac horse fever, whereas percutaneous inoculation with N. risticii did not result in clinical disease.26 In horses, N. risticii targets the GI mucosa.

The resulting lesions are most severe in the

large intestine. The organisms locate within mucosal epithelium as well as macrophages and mast cells of the lamina propria.27 They survive within macrophages by inhibiting production of reactive oxygen species and blocking phagosome–lysosome fusion, thereby avoiding lysosomal digestion.28 Intracellular cAMP increases within infected host cells, leading to decreased luminal reabsorption of sodium ions, increased chloride ion secretion, and decreased water reabsorption in the colon, resulting in profuse watery diarrhea.29 In addition, when infected cells fill with rickettsial organisms, cell lysis occurs. As the disease progresses, fibrinous necrotizing typhlocolitis with severe mucosal ulceration and inflammation of the lamina propria may occur. Vasculitis and intravascular coagulation with perivascular edema in the large intestine are consistent pathologic features of N. risticii infection.30 While the infectious organism has been identified in aquatic snails from many areas of the world, Potomac horse fever is clinically recognized only in North America, South America, and Europe. The disease is most common from late summer through early fall, with a peak incidence in July and August in the northern hemisphere.4 Potomac horse fever is characterized by fever, anorexia, depression, diarrhea, and leukopenia.31 When Potomac horse fever is experimentally induced by oral inoculation, the latent period is typically 1 to 3 weeks, with a biphasic pattern of fever preceding development of diarrhea. While initial fever may be as high as 107˚F (41.7˚C), it is often undetected in horses in the field, and there is no indication of infection until onset of the second episode of fever in conjunction with severe depression and diarrhea.26 Moderate to severe diarrhea is known to occur in 75% of horses with Potomac horse fever and may persist for several days.32 While laminitis is a complicating factor known to develop in 20% to 30% of Potomac horse fever cases, the pathogenesis of this condition remains unclear.4 Other complications of Potomac horse fever may include abortion of infected fetuses, vascular thrombosis, renal failure, and protein-losing enteropathy.

Conclusion Infectious causes of acute colitis have a common clinical presentation despite variation in

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Acute Colitis: Infectious Causes CE associated underlying pathophysiology. Because of the time delay associated with many diagnostic tests, the risk of disease transmission is considerable. Prompt patient isolation and owner education are essential to limiting the chance of disease outbreak. Awareness of the infectious causes of acute colitis should prompt diagnostic testing. If a definitive diagnosis is reached, appropriate treatment can be employed, and the chance for a favorable outcome increases.

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References 1. Rupnik M. Is Clostridium difficile–associated infection a potentially zoonotic and foodborne disease? Clin Microbiol Infect 2007;13:457-459.

2. Clark RG, Fenwick SG, Nicol CM, et al. Salmonella Brandenburg: emergence of a new strain affecting stock and humans in the South Island of New Zealand. N Z Vet J 2004;52:26-36.

3. Larsen J. Acute colitis in adult horses. A review with emphasis on aetiology and pathogenesis. Vet Q 1997;19:72-80.

4. Jones SL. Inflammatory diseases of the gastrointestinal tract causing diarrhea. In: Reed SM, Bayly WM, Sellon DC, eds.

Equine Internal Medicine. 2nd ed. Philadelphia: WB Saunders; 2004:884-913.

5. O’Loughlin EV, Scott RB, Gall DG. Pathophysiology of infectious diarrhea: changes in intestinal structure and function.

J Pediatr Gastroenterol Nutr 1991;12:5-20.

6. Smith BP. Salmonella infection in horses. Compend Contin Educ Pract Vet 1981;3:S4-S17.

7. Baverud V. Clostridium difficile diarrhea: infection control in horses. Vet Clin North Am Equine Pract 2004;20:615-630.

8. Baverud V, Gustafsson A, Franklin A, et al. Clostridium difficile: prevalence in horses and environment, and antimicrobial susceptibility. Equine Vet J 2003;35:465-471.

9. Weese JS, Staempfli HR, Prescott JF. A prospective study of the roles of Clostridium difficile and enterotoxigenic Clostridium perfringens in equine diarrhoea. Equine Vet J 2001;33:403-409.

10. Jones RL, Adney WS, Shideler RK. Isolation of Clostridium difficile and detection of cytotoxin in the feces of diarrheic foals in the absence of antimicrobial treatment. J Clin Microbiol 1987;25:1225-1227.

11. Kelly CP, LaMont JT. Clostridium difficile infection. Annu Rev Med 1998;49:375-390.

12. Starr J. Clostridium difficile associated diarrhoea: diagnosis and treatment. BMJ 2005;331:498-501.

13. Arroyo LG, Weese JS, Staempfli HR. Experimental Clostridium difficile enterocolitis in foals. J Vet Intern Med 2004;18:734-738.

14. Magdesian KG, Dujowich M, Madigan JE, et al. Molecular characterization of Clostridium difficile isolates from horses in an intensive care unit and association of disease severity with strain type.

JAVMA 2006;228:751-755.

15. Alfa MJ, Kabani A, Lyerly D, et al. Characterization of a toxin A– negative, toxin B–positive strain of Clostridium difficile responsible for a nosocomial outbreak of Clostridium difficile –associated diarrhea. J Clin Microbiol 2000;38:2706-2714.

16. Tillotson K, Traub-Dargatz JL, Dickinson CE, et al. Populationbased study of fecal shedding of Clostridium perfringens in broodmares and foals. JAVMA 2002;220:342-348.

17. Ochoa R, Kern SR. The effects of Clostridium perfringens type A enterotoxin in Shetland ponies: clinical, morphologic and clinicopathologic changes. Vet Pathol 1980;17:738-747.

18. McGorum BC, Dixon PM, Smith DG. Use of metronidazole in equine acute idiopathic toxaemic colitis. Vet Rec 1998;142:635-638.

19. Samuel SC, Hancock P, Leigh DA. An investigation into Clostridium perfringens enterotoxin–associated diarrhoea. J Hosp Infect 1991;18:219-230.

20. Jones SL, Spier SJ. Pathophysiology of colonic inflammation and diarrhea. In: Reed S, Bailey SR, eds. Equine Internal Medicine.

Philadelphia: WB Saunders; 1998:660-663.

21. Herholz C, Miserez R, Nicolet J, et al. Prevalence of beta2-toxigenic Clostridium perfringens in horses with intestinal disorders. J Clin Microbiol 1999;37:358-361.

22. Whitlock RH, Palmer JE, Benson CE, et al. Potomac horse fever; clinical characteristics and diagnostic features. Proc Am Assoc Vet Lab Diag 1984:103-124.

23. Park BK, Kim MJ, Kim EH, et al. Identification of trematode cercariae carrying Neorickettsia risticii in freshwater stream snails.

Ann N Y Acad Sci 2003;990:239-247.

24. Chae JS, Pusterla N, Johnson E, et al. Infection of aquatic insects with trematode metacercariae carrying Ehrlichia risticii, the cause of Potomac horse fever. J Med Entomol 2000;37:619-625.

25. Gibson KE, Rikihisa Y, Zhang C, et al. Neorickettsia risticii is vertically transmitted in the trematode Acanthatrium oregonense and horizontally transmitted to bats. Environ Microbiol 2005; 7:203-212.

26. Madigan JE, Pusterla N, Johnson E, et al. Transmission of Ehrlichia risticii, the agent of Potomac horse fever, using naturally infected aquatic insects and helminth vectors: preliminary report.

Equine Vet J 2000;32:275-279.

27. Rikihisa Y, Perry BD, Cordes DO. Ultrastructural study of ehrlichial organisms in the large colons of ponies infected with Potomac horse fever. Infect Immun 1985;49:505-512.

28. Weiss E. Biology of ehrlichiae. Eur J Epidemiol 1991;7:253-258.

29. Rikihisa Y. Growth of Ehrlichia risticii in human colonic epithelial cells. Ann N Y Acad Sci 1990;590:104-110.

30. Cordes DO, Perry BD, Rikihisa Y, et al. Enterocolitis caused

by Ehrlichia sp in the horse (Potomac horse fever). Vet Pathol 1986;23:471-477.

31. Dutta SK, Penney BE, Myrup AC, et al. Disease features in horses with induced equine monocytic ehrlichiosis (Potomac horse fever). Am J Vet Res 1988;49:1747-1751.

32. Ziemer EL, Whitlock RH, Palmer JE, et al. Clinical and hematologic variables in ponies with experimentally induced equine ehrlichial colitis (Potomac horse fever). Am J Vet Res 1987;48:63-67.

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CE TEST 2

This article qualifies for 3 contact hours of continuing education credit from the Auburn University College of Veterinary Medicine. Subscribers may take individual CE tests online and get real-time scores at CompendiumEquine.com. Those who wish to apply this credit to fulfill state relicensure requirements should consult their respective state authorities regarding the applicability of this program.

1. Which of the following is the most commonly reported infectious cause of colitis in horses? a. Salmonella spp b. C. difficile c. C. perfringens d. N. risticii e. none of the above 2. Which statement is not applicable to the pathophysiology of Salmonella enterocolitis? a. Salmonella bacteria are intracellular organisms. b. Systemic salmonellosis is possible by penetration of the bacterium into the bloodstream and the lymphatic system. c. The bacteria trigger an inflammatory response in the cells of the large intestine. d. Some Salmonella spp produce enterotoxin. e. Salmonella spp avoid lysosomal digestion by blocking phagosome–lysosome fusion.

3. Which statement regarding Salmonella spp is true? a. Salmonella spp are gram positive. b. Salmonella spp are obligate anaerobes. c. The virulence of Salmonella bacteria varies tremendously with serotype. d. Salmonella bacteria do not produce toxins. e. S. Typhimurium is rarely associated with disease.

4. Which of the following is not a risk factor for C. difficile–associated colitis in horses? a. presence of a nasogastric tube b. hospitalization c. antimicrobial administration d. laminitis e. dietary change

380

5. Which statement regarding C. difficile is incorrect? a. C. difficile spores can survive for long periods of time in the environment. b. Toxin A is an enterotoxin. c. Different strains of C. difficile produce different types of toxin. d. Toxin A is 1000 times more cytotoxic than toxin B. e. Binary toxin was recognized recently and may have pathogenic significance.

6. Which statement regarding C. perfringens is incorrect? a. C. perfringens type B is a common cause of equine acute colitis. b. α-Toxin is produced by all five types of C. perfringens. c. C. perfringens is a normal inhabitant of the equine GI tract. d. C. perfringens type A can produce enterotoxin. e. C. perfringens can cause colitis due to bacterial overgrowth, which often occurs secondary to a trigger such as antimicrobial administration.

7. Which statement regarding intestinal clostridiosis in horses is incorrect? a. The incidence of equine intestinal clostridiosis is decreasing in North America. b. Intestinal clostridiosis is highly contagious. c. Clostridial spores are difficult to destroy in the environment. d. Antimicrobial therapy is a risk factor for development of intestinal clostridiosis. e. Adult horses can develop clostridialassociated acute colitis.

8. Which statement regarding Potomac horse fever is incorrect? a. The disease is common in late summer through early fall.

b. Laminitis can occur in 20% to 30% of cases. c. N. risticii is transmitted by ticks. d. Not all horses with the disease develop diarrhea. e. Characteristic signs of the disease include fever, depression, anorexia, and leukopenia.

9. Which statement regarding Potomac horse fever is true? a. The disease is recognized worldwide. b. Percutaneous inoculation of N. risticii can result in clinical disease. c. Aquatic water snails are the definitive host for N. risticii. d. The latent period is 1 to 2 days when Potomac horse fever is experimentally induced. e. Complications of the disease include laminitis, abortion, vascular thrombosis, renal failure, and protein-losing enteropathy.

10. Which statement regarding infectious causes of acute colitis in adult horses is incorrect? a. Due to diagnostic limitations for acute colitis, precautionary measures, including patient isolation, should be employed for every case of acute diarrhea. b. The fecal–oral route is the most common way in which the disease is transmitted. c. Many infectious causes of acute colitis are potentially zoonotic. d. There are limited diagnostic tests available for fecal samples in acute colitis cases. e. Laminitis and endotoxemia are potentially fatal sequelae in cases of acute colitis.

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The Final Diagnosis ❯❯ James N. Moore, DVM, PhD, The University of Georgia

The Grada Haus

T

he summer of 1969 was incredible for a lot of folks, including Neil Armstrong and me. Had Neil looked about a quarter of a million miles over his shoulder that summer, he might have seen a young college student landing in Zurich, Switzerland, armed with a couple of years of high-school Spanish and looking for some veterinary-related experience and the chance to spend all the money he’d earned the previous year.

This was a time before anything was easy. Computers, Kinko’s, and the Internet were years away. Having saved

The summer of 1969 was incredible for a lot of folks, including Neil Armstrong and me.

Share your weird or wondrous cases or anecdotes in The Final Diagnosis.

Every equine practitioner has at least one interesting, unusual, or funny story to share. Here’s your opportunity to amaze or amuse your colleagues. For examples of The Final Diagnosis, see CompendiumEquine.com or the last page of each issue.

Accepted submissions are published quickly, and authors receive an honorarium of $100.

E-mail submissions (no more than 650 words) to editor@ CompendiumEquine.com.

my money and convinced my parents that it would be a good idea for me to do what others my age were doing, namely, spend the summer hitchhiking around Europe, I decided that Switzerland was the place to go. This decision was based on the country’s location, which provided access to several other European countries; Switzerland’s reputation for being clean and safe; and my naive conclusion that most people in Switzerland speak English. My parents and I went to the Swiss consulate in San Francisco, where we painstakingly went through a huge stack of Swiss telephone books and wrote down the names of 25 veterinarians. I then went home and, with my mother’s help, typed 25 individual letters asking for the chance to work in their practices. No Internet, no e-mail, no Xeroxed copies—just a Smith Corona and a small bottle of Liquid Paper. The letters went out, and for several weeks, I heard nothing—not a single reply. Finally, I received a letter from an American

equine surgeon, Dr. Bud Fackelman at the veterinary school at the University of Zurich, offering me the chance to work there as a volunteer. He said he’d given in after being forwarded the 10th copy of my letter from Swiss practitioners.

Once my plane landed and I’d located my suitcase, I asked a uniformed airport attendant how to get to the university; that’s when I got my first dose of “Nicht verstehen.” Undaunted, I lugged my suitcase through the airport and posed the same question to a policeman directing traffic near the front of the airport; same response.

Because a lot of German-speaking people were boarding a large city-type bus, I did the same. As we drove through small villages and neighborhoods, people occasionally got off the bus, and a few boarded.

As we neared Zurich, more folks tended to exit. Finally, as we approached the train station, most people rose to exit. I did the same and found myself in the middle of downtown Zurich.

After getting “Nicht verstehen” from a magazine vendor at a street-side stand, I started to worry a bit. Here I was, by myself, mid- to late-afternoon in a city where nobody seemed to understand me, not knowing how to find the university. Being resourceful, however, I looked around and spotted a bar. I thought to myself, Americans go to bars—the bartender will speak English.

I dragged my suitcase across the street, entered the bar, and went straight up to the bartender. This time, my approach was a bit different.

“Do you speak English?” I asked.

“A little,” he replied.

“Can you tell me where the University of Zurich is?”

“Come here,” he said, heading toward the door.

CompendiumEquine.com | October 2009 | Compendium Equine: Continuing Education for Veterinarians®

383

The Final Diagnosis When we got to the sidewalk, he pointed down the street, gesturing with two fingers on his left hand, and said, “Here, zwei...”

“Blocks?” I guessed.

“Ja. Ja. Blocks. Und, rechts,” with his hand pointing strongly to the right.

“Right,” I guessed again.

“Ja. Ja. Right. Und, drei…b…b…b…”

“Blocks?” It was my turn again.

“Ja. Ja. Blocks. Und, links.” This time, his hand pointed to the left.

“Left?”

“Ja. Ja. Left. Und, grada haus,” and he headed back into the bar.

As directed, I walked down the street two blocks, hung a rechts, dragged my suitcase another three blocks, and hung a links. Then, I started looking for the Grada Haus he’d mentioned. I imagined a large, ornate building, something impressive and important, possibly an old government building that was now part of the university.

After about 15 minutes of not seeing what I imagined, I dug out the English– German dictionary from my suitcase and looked up the words for “Where is?,” which are “Wo ist?” The dictionary suggested they be pronounced “Vo eest,” so I practiced them silently until they sounded reasonably German.

Having regained a bit of confidence, I stopped the next unsuspecting Swiss gentleman heading toward me by saying, “Vo eest Grada Haus?” He kindly pointed down the street the way I was heading, which reassured me that I was on track.

I repeated the process every couple of blocks, asking people the same question about Grada Haus and receiving the same answer. Finally, I came to a sign for the University of Zurich, found someone who spoke English fluently, and then almost died when I learned that the vet school was actually near the airport.

The story doesn’t end there, though. One morning about 3 weeks later in the equine clinic, one of the vet students who spoke excellent English said “Grada Haus” while talking with one of his classmates. When I asked him what it meant, he kindly translated, “Geradeaus means straight ahead.”

Neil would have been amused.

384

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Company

Product

Page #

American Association of Equine Practitioners

55th Annual Convention

Inside back cover

Bayer HealthCare Animal Health

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339

BET Pharm

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357

Thyroxine and Altrenogest

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GLC Direct

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349

Intervet/Schering-Plough Animal Health

PreveNile

343

Luitpold Pharmaceuticals, Inc

Adequan i.m.

345

Meds for Vets

Compounding Pharmacy

359

Merial

GastroGard

346, 347

Modulog

Cedar Siding System

381

Platinum Performance, Inc

Platinum Performance

341

Shank’s Veterinary Equipment

Surgery Tables

381

Triple Crown Nutrition, Inc

Triple Crown Senior

Back cover

Universal Ultrasound

MYLAB Ultrasound, UMS 900, TERAVET T3000

Inside front cover

Veterinary Learning Systems

A Guide to Equine Joint Injection and Regional Anesthesia

362

Equine Oxygen Therapy, LLC

Veterinary Technician

384

VetLearn.com

351

Compendium Equine: Continuing Education for Veterinarians® | October 2009 | CompendiumEquine.com

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