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2009 Vol 31(1)
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Anesthesia Internal Medicine
Nora S. Matthews, DVM, DACVA Dana G. Allen, DVM, MSc, DACVIM
Texas A&M University Ontario Veterinary College BOARD OF
Cardiology Internal Medicine and Emergency/ VETERINARY
Bruce Keene, DVM, MSc, DACVIM Critical Care PRACTITIONERS
North Carolina State University Alison R. Gaynor, DVM, DACVIM (ABVP) REVIEW
(Internal Medicine), DACVECC
Clinical Chemistry, Hematology,
North Grafton, Massachusetts
Betsy Welles, DVM, PhD, DACVP Nephrology Eric Chafetz, DVM, DABVP
Auburn University Catherine E. Langston, DVM, ACVIM (Canine/Feline)
Animal Medical Center
Dentistry Vienna Animal Hospital
New York, New York
Gary B. Beard, DVM, DAVDC Vienna, Virginia
Auburn University Neurology Canine and Feline Medicine
EDITOR IN CHIEF R. Michael Peak, DVM, DAVDC
Curtis W. Dewey, DVM, MS, DACVIM
(Neurology), DACVS Henry E. Childers, DVM,
Douglass K. Macintire, The Pet Dentist—Tampa Bay Veterinary
Cornell University Hospital for Animals
Dentistry DABVP (Canine/Feline)
DVM, MS, DACVIM, DACVECC
Largo, Florida Oncology Cranston Animal Hospital
Department of Clinical Sciences Ann E. Hohenhaus, DVM, DACVIM Cranston, Rhode Island
College of Veterinary Medicine Emergency/Critical Care and
(Oncology and Internal Medicine) Canine and Feline Medicine
Auburn University, AL 36849 Respiratory Medicine
Animal Medical Center
Lesley King, MVB, MRCVS, DACVECC,
New York, New York
DACVIM David E. Harling, DVM,
University of Pennsylvania Gregory K. Ogilvie, DVM, DACVIM DABVP (Canine/Feline),
(Internal Medicine and Oncology) DACVO
Endocrinology and Metabolic Disorders
CVS Angel Care Cancer Center and Special Reidsville Veterinary Hospital
Marie E. Kerl, DVM, ACVIM, ACVECC
Care Foundation for Companion Animals Reidsville, North Carolina
University of Missouri-Columbia
San Marcos, California Canine and Feline Medicine,
ADVISORY Philip H. Kass, DVM, MPVM, MS, PhD,
David A. Wilkie, DVM, MS, DACVO
The Ohio State University Jeffrey Katuna, DVM, DABVP
University of California, Davis
MEMBERS Parasitology Wellesley-Natick Veterinary
Byron L. Blagburn, MS, PhD Hospital
Behavior Auburn University Natick, Massachusetts
Thomas N. Tully, Jr, DVM, MS, DABVP
Sharon L. Crowell-Davis, (Avian), ECAMS David S. Lindsay, PhD
Canine and Feline Medicine
DVM, PhD, DACVB Louisiana State University Virginia Polytechnic Institute
The University of Georgia and State University Robert J. Neunzig, DVM,
Douglas R. Mader, MS, DVM, DABVP (DC) Pharmacology
Dermatology Marathon Veterinary Hospital Katrina L. Mealey, DVM, PhD, DACVIM,
The Pet Hospital
Craig E. Grifﬁn, DVM, Marathon, Florida DACVCP Bessemer City, North Carolina
Washington State University Canine and Feline Medicine
DACVD Small Mammals
Animal Dermatology Clinic Karen Rosenthal, DVM, MS, DABVP Rehabilitation and Physical Therapy
San Diego, California (Avian) Darryl Millis, MS, DVM, DACVS
University of Pennsylvania University of Tennessee
Wayne S. Rosenkrantz, Feline Medicine Surgery Compendium is a
DVM, DACVD Michael R. Lappin, DVM, PhD, Philipp Mayhew, BVM&S, MRCVS, refereed journal. Articles
Animal Dermatology Clinic DACVIM (Internal Medicine) DACVS
Colorado State University Columbia River Veterinary Specialists
published herein have
Tustin, California been reviewed by at least
Margie Scherk, DVM, DAVBP
(Feline Medicine) C. Thomas Nelson, DVM
two academic experts on
Nutrition the respective topic and
Cats Only Veterinary Clinic Animal Medical Center
Kathryn E. Michel, DVM, Vancouver, British Columbia Anniston, Alabama by an ABVP practitioner.
Gastroenterology Surgery and Orthopedics
University of Pennsylvania
Debra L. Zoran, DVM, MS, PhD, Ron Montgomery, DVM, MS, DACVS
DACVIM (Internal Medicine) Auburn University
Surgery Texas A&M University Any statements, claims, or product
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SevoFlo® (sevoflurane) anesthesia—with expert service, support and
training—is smart, efficient and profitable for your practice.
Only SevoFlo— You’re probably familiar with SevoFlo. But, do you realize how Abbott Animal
available through Health’s exceptional service and product support helps you, your patients and
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unique benefits: SevoFlo and Abbott Animal Health can help your surgical suite run efficiently
1. A minimum of and profitably. Our team of local representatives provides support and advice.
300 ppm water In addition, our technical support department and panel of anesthesiologists
2. Shatter-resistant are standing by to discuss techniques and equipment. Abbott Animal Health
PEN bottles also helps educate you and your staff by providing “lunch-and-learns,” in-clinic
3. Local Abbott training materials and CE sponsorships—we’re committed to the veterinary
and expert advice
4. Commitment To learn more about SevoFlo, our other anesthetics and our commitment
to serving you, contact Abbott Animal Health Customer Service at
888-299-7416 or visit www.abbottanimalhealth.com.
Important Information: How Supplied: SevoFlo is packaged in amber colored bottles containing 250 mL sevoflurane. Indications:
SevoFlo is indicated for induction and maintenance of general anesthesia in dogs. Warnings, Precautions, and Contraindications:
Like other inhalation anesthetics, sevoflurane is a profound respiratory depressant. Respiration must be monitored closely in the
dog and supported when necessary with supplemental oxygen and/or assisted ventilation. Due to sevoflurane’s low solubility
in blood, increasing concentration may result in rapid hemodynamic changes compared to other volatile anesthetics. SevoFlo
is contraindicated in dogs with a known sensitivity to sevoflurane or other halogenated agents. Adverse Reactions: The most
frequently reported adverse reactions during maintenance anesthesia were hypotension, followed by tachypnea, muscle
tenseness, excitation, apnea, muscle fasciculations and emesis. See package insert for full prescribing information.
See Page 4 for Product Information Summary
©2008 Abbott Laboratories
6. PRECAUTIONS: Halogenated volatile anesthetics can react with desiccated decreased at hourly intervals, from 500 mL/min (36 and 18 ppm Compound A) to 250
SevoFlo® 5458 carbon dioxide (CO2) absorbents to produce carbon monoxide (CO) that may mL/min (43 and 31 ppm) to 50 mL/min (61 and 48 ppm).8
(sevoflurane) result in elevated carboxyhemoglobin levels in some patients. To prevent this Fluoride ion metabolite: Sevoflurane is metabolized to hexafluoroisopropanol (HFIP)
reaction, sevoflurane should not be passed through desiccated soda lime or with release of inorganic fluoride and CO2. Fluoride ion concentrations are influenced by
Inhalation Anesthetic For Use in Dogs
barium hydroxide lime. the duration of anesthesia and the concentration of sevoflurane. Once formed, HFIP is
Caution: Federal law restricts this drug to use by or on the order of a
Replacement of Desiccated CO2 Absorbents: When a clinician suspects rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite. No other
that the CO2 absorbent may be desiccated, it should be replaced before metabolic pathways for sevoflurane have been identified. In humans, the fluoride ion
DESCRIPTION: SevoFlo (sevoflurane), a volatile liquid, is a halogenated
administration of sevoflurane. The exothermic reaction that occurs with half-life was prolonged in patients with renal impairment, but human clinical trials
general inhalation anesthetic drug. Its chemical name is fluoromethyl 2,2,2-
sevoflurane and CO2 absorbents is increased when the CO2 absorbent contained no reports of toxicity associated with elevated fluoride ion levels. In a study in
trifluoro-l- (trifluoromethyl) ethyl ether, and its structural formula is:
becomes desiccated, such as after an extended period of dry gas flow through which 4 dogs were exposed to 4% sevoflurane for 3 hours, maximum serum fluoride
the CO2 absorbent canisters. Extremely rare cases of spontaneous fire in the concentrations of 17.0-27.0 mcmole/L were observed after 3 hours of anesthesia.
respiratory circuit of the anesthesia machine have been reported during Serum fluoride fell quickly after anesthesia ended, and had returned to baseline by 24
sevoflurane use in conjunction with the use of a desiccated CO2 absorbent, hours post-anesthesia. In a safety study, eight healthy dogs were exposed to
specifically those containing potassium hydroxide (e.g. BARALYME). sevoflurane for 3 hours/day, 5 days/week for 2 weeks (total 30 hours exposure) at a
Potassium hydroxide containing CO2 absorbents are not recommended for use flow rate of 500 mL/min in a semi-closed, rebreathing system with soda lime. Renal
Sevoflurane Physical Constants are: with sevoflurane. An unusually delayed rise in the inspired gas concentration toxicity was not observed in the study evaluation of clinical signs, hematology, serum
Molecular weight 200.05 (decreased delivery) of sevoflurane compared with the vaporizer setting may chemistry, urinalysis, or gross or microscopic pathology.
Boiling point at 760 mm Hg 58.6°C indicate excessive heating of the CO2 absorbent canister and chemical DRUG INTERACTIONS: In the clinical trial, sevoflurane was used safely in dogs that
Specific gravity at 20°C 1.520-1.525 g/mL breakdown of sevoflurane. The color indicator of most CO2 absorbent may not received frequently used veterinary products including steroids and heartworm and flea
Vapor pressure in mm Hg at 20°C 157 change upon desiccation. Therefore, the lack of significant color change preventative products.
at 25°C 197 should not be taken as an assurance of adequate hydration. CO2 absorbents Intravenous Anesthetics: Sevoflurane administration is compatible with barbiturates,
at 36°C 317 should be replaced routinely regardless of the state of the color indicator. propofol and other commonly used intravenous anesthetics. Benzodiazepines and
Distribution Partition Coefficients at 37°C: Opioids: Benzodiazepines and opioids would be expected to decrease the MAC of
The use of some anesthetic regimens that include sevoflurane may result in
Blood/Gas 0.63-0.69 sevoflurane in the same manner as other inhalational anesthetics. Sevoflurane is
bradycardia that is reversible with anticholinergics. Studies using sevoflurane
Water/Gas 0.36 compatible with benzodiazepines and opioids as commonly used in surgical practice.
anesthetic regimens that included atropine or glycopyrrolate as premedicants
Olive Oil/Gas 47-54 Phenothiazines and Alpha2-Agonists: Sevoflurane is compatible with phenothiazines
showed these anticholinergics to be compatible with sevoflurane in dogs.
Brain/Gas 1.15 and alpha2- agonists as commonly used in surgical practice.
During the induction and maintenance of anesthesia, increasing the
Mean Component/Gas Partition Coefficients at 25°C for Polymers Used In a laboratory study, the use of the acepromazine/oxymorphone/ thiopental/sevoflurane
concentration of sevoflurane produces dose dependent decreases in blood
Commonly in Medical Applications: anesthetic regimen resulted in prolonged recoveries in eight (of 8) dogs compared to
pressure and respiratory rate. Due to sevoflurane’s low solubility in blood,
Conductive rubber 14.0 recoveries from sevoflurane alone.
these changes may occur more rapidly than with other volatile anesthetics.
Butyl rubber 7.7 CLINICAL EFFECTIVENESS:
Excessive decreases in blood pressure or respiratory depression may be
Polyvinyl chloride 17.4 The effectiveness of sevoflurane was investigated in a clinical study involving 196 dogs.
related to depth of anesthesia and may be corrected by decreasing the
Polyethylene 1.3 Thirty dogs were mask-induced with sevoflurane using anesthetic regimens that
inspired concentration of sevoflurane. RESPIRATION MUST BE MONITORED
included various premedicants. During the clinical study, one hundred sixty-six dogs
CLOSELY IN THE DOG AND SUPPORTED WHEN NECESSARY WITH
Sevoflurane is nonflammable and nonexplosive as defined by the requirements of received sevoflurane maintenance anesthesia as part of several anesthetic regimens
SUPPLEMENTAL OXYGEN AND/OR ASSISTED VENTILATION. The low
International Electrotechnical Commission 601-2-13. Sevoflurane is a clear, that used injectable induction agents and various premedicants. The duration of
solubility of sevoflurane also facilitates rapid elimination by the lungs.
colorless, stable liquid containing no additives or chemical stabilizers. anesthesia and the choice of anesthetic regimens were dependent upon the procedures
The use of sevoflurane in humans increases both the intensity and duration of
Sevoflurane is nonpungent. It is miscible with ethanol, ether, chloroform and that were performed. Duration of anesthesia ranged from 16 to 424 minutes among the
neuromuscular blockade induced by nondepolarizing muscle relaxants. The
petroleum benzene, and it is slightly soluble in water. Sevoflurane is stable when individual dogs. Sevoflurane vaporizer concentrations during the first 30 minutes of
use of sevoflurane with nondepolarizing muscle relaxants has not been
stored under normal room lighting condition according to instructions. maintenance anesthesia were similar among the various anesthetic regimens. The
evaluated in dogs.
INDICATIONS: SevoFlo is indicated for induction and maintenance of general quality of maintenance anesthesia was considered good or excellent in 169 out of 196
Compromised or debilitated dogs: Doses may need adjustment for geriatric or
anesthesia in dogs. dogs. The table shows the average vaporizer concentrations and oxygen flow rates
debilitated dogs. Because clinical experience in administering sevoflurane to
DOSAGE AND ADMINISTRATION: Inspired Concentration: The delivered during the first 30 minutes for all sevoflurane maintenance anesthesia regimens:
dogs with renal, hepatic and cardiovascular insufficiency is limited, its safety in
concentration of SevoFlo should be known. Since the depth of anesthesia may these dogs has not been established.
be altered easily and rapidly, only vaporizers producing predictable percentage Average Average Average Average
Breeding dogs: The safety of sevoflurane in dogs used for breeding purposes, Vaporizer Vaporizer Oxygen Oxygen
concentrations of sevoflurane should be used. Sevoflurane should be vaporized during pregnancy, or in lactating bitches, has not been evaluated. Concentrations Concentrations Flow Flow
using a precision vaporizer specifically calibrated for sevoflurane. Sevoflurane Neonates: The safety of sevoflurane in young dogs (less than 12 weeks of among among Rates Rates
contains no stabilizer. Nothing in the drug product alters calibration or operation age) has not been evaluated. Anesthetic Individual among among
of these vaporizers. The administration of general anesthesia must be HUMAN SAFETY: Not for human use. Keep out of reach of children.
Regimens Dogs Anesthetic Individual
individualized based on the patient’s response. WHEN USING SEVOFLURANE, Regimens Dogs
Operating rooms and animal recovery areas should be provided with 3.31 - 3.63% 1.6 - 5.1% 0.97 - 1.31 0.5 - 3.0
PATIENTS SHOULD BE CONTINUOUSLY MONITORED AND FACILITIES adequate ventilation to prevent the accumulation of anesthetic vapors. L/minute L/minute
FOR MAINTENANCE OF PATENT AIRWAY, ARTIFICIAL VENTILATION, AND There is no specific work exposure limit established for sevoflurane. However,
OXYGEN SUPPLEMENTATION MUST BE IMMEDIATELY AVAILABLE. the National Institute for Occupational Safety and Health has recommended an During the clinical trial, when a barbiturate was used for induction, the times to
Replacement of Desiccated CO2 Absorbents: When a clinician suspects that 8 hour time-weighted average limit of 2 ppm for halogenated anesthetic agents extubation, sternal recumbency and standing recovery were longer for dogs that
the CO2 absorbent may be desiccated, it should be replaced. An exothermic in general. Direct exposure to eyes may result in mild irritation. If eye exposure received anesthetic regimens containing two preanesthetics compared to regimens
reaction occurs when sevoflurane is exposed to CO2 absorbents. This reaction is containing one preanesthetic. Recovery times were shorter when anesthetic regimens
occurs, flush with plenty of water for 15 minutes. Seek medical attention if
increased when the CO2 absorbent becomes desiccated (see PRECAUTIONS). irritation persists. Symptoms of human overexposure (inhalation) to used sevoflurane or propofol for induction. The quality of recovery was considered good
Premedication: No specific premedication is either indicated or contraindicated sevoflurane vapors include respiratory depression, hypotension, bradycardia, or excellent in 184 out of 196 dogs. Anesthetic regimen drug dosages, physiological
with sevoflurane. The necessity for and choice of premedication is left to the shivering, nausea and headache. If these symptoms occur, remove the responses, and the quality of induction, maintenance and recovery were comparable
discretion of the veterinarian. Preanesthetic doses for premedicants may be between 10 sighthounds and other breeds evaluated in the study. During the clinical
individual from the source of exposure and seek medical attention. The
lower than the label directions for their use as a single medication.1 material safety data sheet (MSDS) contains more detailed occupational safety study there was no indication of prolonged recovery times in the sighthounds.
Induction: For mask induction using sevoflurane alone, inspired concentrations information. For customer service, adverse effects reporting, and/or a HOW SUPPLIED: SevoFlo (sevoflurane) is packaged in amber colored bottles
up to 7% sevoflurane with oxygen are employed to induce surgical anesthesia in copy of the MSDS, call (888) 299-7416. containing 250 mL sevoflurane, List 5458.
the healthy dog. These concentrations can be expected to produce surgical STORAGE CONDITIONS: Store at controlled room temperature 15°-30°C (59°-86°F).
CLINICAL PHARMACOLOGY: Sevoflurane is an inhalational anesthetic
anesthesia in 3 to 14 minutes. Due to the rapid and dose dependent changes agent for induction and maintenance of general anesthesia. The Minimum REFERENCES:
in anesthetic depth, care should be taken to prevent overdosing. Alveolar Concentration (MAC) of sevoflurane as determined in 18 dogs is 1. Plumb, D.C. ed., Veterinary Drug Handbook, Second Edition, University of Iowa
Respiration must be monitored closely in the dog and supported when 2.36%.2 MAC is defined as that alveolar concentration at which 50% of healthy Press, Ames, IA: p. 424 (1995).
necessary with supplemental oxygen and/or assisted ventilation. patients fail to respond to noxious stimuli. Multiples of MAC are used as a 2. Kazama, T. and Ikeda, K., Comparison of MAC and the rate of rise of alveolar
Maintenance: SevoFlo may be used for maintenance anesthesia following mask guide for surgical levels of anesthesia, which are typically 1.3 to 1.5 times the concentration of sevoflurane with halothane and isoflurane in the dog. Anesthesiology.
induction using sevoflurane or following injectable induction agents. The MAC value. Because of the low solubility of sevoflurane in blood (blood/gas 68: 435-437 (1988).
concentration of vapor necessary to maintain anesthesia is much less than that partition coefficient at 37°C = 0.63-0.69), a minimal amount of sevoflurane is 3. Scheller, M.S., Nakakimura, K., Fleischer, J.E. and Zornow, M.H., Cerebral effects of
required to induce it. Surgical levels of anesthesia in the healthy dog may be required to be dissolved in the blood before the alveolar partial pressure is in sevoflurane in the dog: Comparison with isoflurane and enflurane. Brit. J. Anesthesia
maintained with inhaled concentrations of 3.7-4.0% sevoflurane in oxygen in the equilibrium with the arterial partial pressure. During sevoflurane induction, 65: 388-392 (1990).
absence of premedication and 3.3-3.6% in the presence of premedication. The there is a rapid increase in alveolar concentration toward the inspired 4. Frink, E.J., Morgan, S.E., Coetzee, A., Conzen, P.F. and Brown, B.R., Effects of
use of injectable induction agents without premedication has little effect on the concentration. Sevoflurane produces only modest increases in cerebral blood sevoflurane, halothane, enflurane and isoflurane on hepatic blood flow and oxygenation
concentrations of sevoflurane required for maintenance. Anesthetic regimens that flow and metabolic rate, and has little or no ability to potentiate seizures.3 in chronically instrumented greyhound dogs. Anesthesiology 76: 85-90 (1992).
include opioid, alpha2-agonist, benzodiazepine or phenothiazine premedication Sevoflurane has a variable effect on heart rate, producing increases or 5. Kazama, T. and Ikeda, K., The comparative cardiovascular effects of sevoflurane
will allow the use of lower sevoflurane maintenance concentrations. decreases depending on experimental conditions.4,5 Sevoflurane produces with halothane and isoflurane. J. Anesthesiology 2: 63-8 (1988).
CONTRAINDICATIONS: SevoFlo is contraindicated in dogs with a known dose-dependent decreases in mean arterial pressure, cardiac output and 6. Bernard, J. M., Wouters, P.F., Doursout, M.F., Florence, B., Chelly, J.E. and Merin,
sensitivity to sevoflurane or other halogenated agents. myocardial contraction.6 Among inhalation anesthetics, sevoflurane has low R.G., Effects of sevoflurane on cardiac and coronary dynamics in chronically
WARNINGS: Sevoflurane is a profound respiratory depressant. DUE TO THE arrhythmogenic potential.7 Sevoflurane is chemically stable. No discernible instrumented dogs. Anesthesiology 72: 659-662 (1990).
RAPID AND DOSE DEPENDENT CHANGES IN ANESTHETIC DEPTH, degradation occurs in the presence of strong acids or heat. Sevoflurane reacts 7. Hayaski, Y., Sumikawa, K., Tashiro, C., Yamatodani, A. and Yoshiya, I.,
RESPIRATION MUST BE MONITORED CLOSELY IN THE DOG AND through direct contact with CO2 absorbents (soda lime and barium hydroxide Arrhythmogenic threshold of epinephrine during sevoflurane, enflurane and isoflurane
SUPPORTED WHEN NECESSARY WITH SUPPLEMENTAL OXYGEN lime) producing pentafluoroisopropenyl fluoromethyl ether (PIFE, C4H2F6O), anesthesia in dogs. Anesthesiology 69: 145-147 (1988).
AND/OR ASSISTED VENTILATION. also known as Compound A, and trace amounts of pentafluoromethoxy 8. Muir, W.W. and Gadawski, J., Cardiorespiratory effects of low-flow and closed circuit
In cases of severe cardiopulmonary depression, discontinue drug administration, isopropyl fluoromethyl ether (PMFE, C5H6F6O), also known as Compound B. inhalation anesthesia, using sevoflurane delivered with an in-circuit vaporizer and
ensure the existence of a patent airway and initiate assisted or controlled Compound A: The production of degradants in the anesthesia circuit results concentrations of compound A. Amer. J. Vet. Res. 59 (5): 603-608 (1998).
ventilation with pure oxygen. Cardiovascular depression should be treated with from the extraction of the acidic proton in the presence of a strong base
plasma expanders, pressor agents, antiarrhythmic agents or other techniques as (potassium hydroxide and/or NaOH) forming an alkene (Compound A) from NADA 141-103, Approved by FDA
appropriate for the observed abnormality. Due to sevoflurane’s low solubility in SevoFlo® is a registered trademark of Abbott Laboratories.
blood, increasing the concentration may result in rapid changes in anesthetic Compound A is produced when sevoflurane interacts with soda lime or barium Manufactured by Abbott Laboratories, North Chicago, IL
depth and hemodynamic changes (dose dependent decreases in respiratory rate hydroxide lime. Reaction with barium hydroxide lime results in a greater 60064, USA
and blood pressure) compared to other volatile anesthetics. Excessive decreases production of Compound A than does reaction with soda lime. Its concentration Product of Japan
in blood pressure or respiratory depression may be corrected by decreasing or in a circle absorber system increases with increasing sevoflurane
discontinuing the inspired concentration of sevoflurane. Under license from
concentrations and with decreasing fresh gas flow rates. Sevoflurane Maruishi Pharmaceutical Co., LTD
Potassium hydroxide containing CO2 absorbents (e.g. BARALYME®) are not degradation in soda lime has been shown to increase with temperature. Since 2-3-5, Fushimi-Machi, Chuo-Ku,
recommended for use with sevoflurane. the reaction of carbon dioxide with absorbents is exothermic, this temperature Osaka, Japan
ADVERSE REACTIONS: The most frequently reported adverse reactions during increase will be determined by the quantities of CO2 absorbed, which in turn
maintenance anesthesia were hypotension, followed by tachypnea, muscle For customer service call (888) 299-7416.
will depend on fresh gas flow in the anesthetic circle system, metabolic status
tenseness, excitation, apnea, muscle fasciculations and emesis. of the patient and ventilation. Although Compound A is a dose-dependent
Infrequent adverse reactions include paddling, retching, salivation, cyanosis, ©Abbott 8/2006
nephrotoxin in rats, the mechanism of this renal toxicity is unknown. Two Taken from Commodity Number 03-5474/R6, SevoFlo, sevoflurane, package insert, January 11, 2007
premature ventricular contractions and excessive cardiopulmonary depression. spontaneously breathing dogs under sevoflurane anesthesia showed
Transient elevations in liver function tests and white blood cell count may occur
increases in concentrations of Compound A as the oxygen flow rate was
with sevoflurane, as with the use of other halogenated anesthetic agents.
SEVO-152 January 2007 page 1 of 1 ©2007 Abbott Laboratories
Each CE article is accredited for 3 contact hours by
Auburn University College of Veterinary Medicine. Section Name
January 2009 Vol 31(1)
8 Understanding Behavior CompendiumVet.com | Peer Reviewed | Listed in MEDLINE
Behavior Assessment: The First Appointment
❯❯ Sharon L. Crowell-Davis
Once a behavior prob- An In-Depth Look FREE
lem has been identi-
ﬁed and described, the
14 The Diagnostic Approach to CE
circumstances in which it Fever of Unknown Origin in D
occurs must be clariﬁed. ❯❯ Julie Flood
This is the second article
in this series on behav- FREE
ior patient assessment. 26 The Diagnostic Approach to CE
Fever of Unknown Origin in C t
22 Focus on Nutrition
NEW ❯❯ Julie Flood
Using a Diet History to Improve Fever is a common clinical sign in dogs and
Adherence to Dietary Recommendations
i cats, but its cause is not always apparent.
❯❯ Kathryn E. Michel These articles present a thorough overview
of physical examination ﬁndings and diag-
The ﬁrst article in this quarterly series explains
nostic tests that can help guide diagnosis of
how to effectively use diet history forms and
the underlying condition.
what information is most important.
33 Immunosuppressive Therapy for Canine
Immune-Mediated Hemolytic Anemia FREE
❯❯ Suliman Al-Ghazlat CE
The author describes the range of
current treatment options for dogs with this
potentially deadly condition.
47 Focus on Nutrition
Sample Diet History Form
This form is also downloadable from
6 Editorial: Clinical Snapshot
Focus on Nutrition PAGE 11
❯❯ Kathryn E. Michel
11 Clinical Snapshot
A Dog with “Bumps”
on its Skin
On the Cover
❯❯ Karen A. Moriello Starting on page 14, Dr. Julie Flood de-
scribes the diagnostic approach to fever
of unknown origin in dogs and cats.
32 Product Forum 45 Classiﬁed Advertising Supplemental material to both articles
45 Market Showcase 46 Index to Advertisers is available at CompendiumVet.com.
❯❯ Kathryn E. Michel, DVM, MS, DACVN, University of Pennsylvania
Focus on Nutrition
The goal of this new quarterly column is to provide veterinary
health professionals with state-of-the-art information on best
practices for the nutritional management of companion animals.
D etermining and implementing the The articles will be written by members
appropriate dietary management of of the ACVN, the recognized specialty board
companion animals have long been in this area of expertise. The column will
recognized by the veterinary profession as also include information about the ACVN, the
key components of maintaining wellness and services its diplomates can offer to practicing
treating disease. Now, pet owners are increas- veterinarians, and resources for those who
ingly aware of the beneﬁts and risks that cer- may be interested in specializing in the ﬁeld
tain dietary habits may entail. In the present of nutrition.
“information age,” it is a growing challenge for We all know that diet is a subject of great
veterinary practitioners to stay abreast of this concern to many pet owners and one about
dynamic ﬁeld to be able to offer their clients which people often hold strong opinions. It
accurate information about companion animal can be a sensitive subject to broach, and it is
nutrition and diet choices and their patients often difﬁcult to get clients to adhere to the
the latest advances in nutritional management. dietary recommendations we make for their
pets. I hope that Focus on Nutrition will help
We all know that diet is a subject of great veterinary health professionals become more
concern to many pet owners and one about informed on entering into and feel more con-
a dialogue on diet
which people often hold strong opinions. and dietary management with their clients
to ensure the best possible outcome for their
In order to help practitioners meet this patients.
challenge, this issue of Compendium is launch-
ing the Focus on Nutrition series in collabora-
tion with the American College of Veterinary SHARE YOUR COMMENTS
Nutrition (ACVN). This new column, which will Have something to say about this
appear quarterly, is devoted to current topics in editorial or topic? Let us know:
small animal nutrition. The goal is to provide
veterinary health professionals with state-of-
the-art information on best practices for the FAX 800-556-3288
nutritional management of companion animals,
both to maintain wellness and to treat disease.
6 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
2009 Vol 31(1)
and bird owners, these metals are frequently
found in the environments of pet and aviary EXCLUSIVE
❯❯ Supplements: The Diagnostic birds, and intoxications are common. Once VIDEO
Approach to Fever of Unknown diagnosed, intoxication can be effectively
Origin in Dogs and Cats treated by (1) preventing further exposure,
(2) administering chelating drugs, and (3)
❯❯ Julie Flood
providing symptomatic and supportive care.
Diagnosing the cause of fever of unknown
origin (FUO) can require a battery of tests. Date: __________
Owner Information What is__________
Name: __________ Greed toward
__________ Indifference Table foods
Email address: __________ Has your or scaps;
__________ __________ attitude
This supplemental material elaborates on
__________ ______ ce ______ home-p
Phone (home): ________________ food change ______ repared
__________ ________________ ______ foods s
__________ ______ ______ d? If so, ______ ______
Phone (cell): __________ ______ ______ describe: ______ ______
______ ______ ______ ______
__________ ______ ______ ______ ______ ______
Best time to ______
__________ ______ ______ ______ ______ ______ ______
call:________________ __________ ______ ____ ______ ______
__ ______ ______ ______ ______
________________ ______ ______ ______ ______
______ ___ ______ ____ ______ ______ ____
Pet Information ______ ______ ______ ______
If you have ______ ______ ______ ______ _ ______
______ ______ ______ ______ ____
Name: __________ other pets, ______ ____ ______ ______ ______
is this pet ______ Dietary ______ ______ _______
__________ Domina domina ______ supplem ______ ____
__________ ____ ______
Species: __________ ____ Age: nt
Has your ________Submissive left out or submissive
__________ pet to
for your pet duringthem? ______ give pills ____
Gender: _ Breed: __________ recently ______
some of the diagnostic tools that can be used
Male Female ______ lost Does your
_________ or gained the day? ______ ______
Neutered/spayed: ______ pet have
weight? access to other, Yes______ No ______
Current weight: ______ If ______ ______ ______
__________ Yes No____________ (e.g., treats fed so, please describ unmonitored ______ ______
Body condition ___ Usual ____________ ______ by neighbor, food e:
❯❯ Focus on Nutrition:
______ ______ ______ ______
______ _______________ Yes No ______ left for outdoor______
______ cats)? ______
Evidence of muscle ______ ______ ____ ______ ______
wasting ______ If yes, please ____________ ______ ______
______ ______ ______
______ ______ ______
Reason for Visit Have there Severe ______ __________ ______
______ ____________________ ________________________________
List anythin ______
been any ______ __________ g else given ______
_____________ ______ recent change
__________ ______ __________
______ __________ by mouth ______
__________ ______ __________
s in activity ______ ______ (e.g., medica ______
__________ ______ ____
__________ ______ __
❯❯ CAPC 2008 Road Show
__________ ______ __________ level? ______ __________
______ __________ ____________ ations):
__________ ______ _________ ______ __________ ____ ______ __
__________ ______ ______ __________ ______ ______
______ __________ ____________ __________ ____________ __________ ______
or may become available for patients with
__________ ______ __________ ______ ____________ ______ ______
__________ ________ ______ ____
__________ ______ ______ ____
__________ ______ ______
Have you __________ ______If you have more than ______
__________ ______ __________ ____________ ______
observe ______ one pet, do they ____________
____ __ ______
Household Demograph d any__ food?
of the followin
______ have access ______ ______
ics Nausea/salivat Yes ______ ______ to each other’s ______ ______
How many adults g: No If____ ______
yes, please describe: ______ ______ _____ ____
Sample Diet History
are in your household? Difﬁcul __________ ______ ______
How many children __________ ty chewin __________ ____________ ______
are in your household, Dyspha g
_________ __________ __________ ______ ______
__________ __________ ______ ______
__________ and how old are
gia __________ Is your pet’s
No __ ______ ______
__________ they? __________ __________ current ______
__________ Vomitin Yes
__________ __________ a change
__________ __________g __________
No Yes __ from its _____
__________ __ __________ __________ No typical diet?
__________ __________ al
__________ __________ If so, please
__________ __ __________ __________ describe
__________ __________ change
Constip __________ ____________
FUO, the differential diagnosis, and tips on
__________ __________ ation No __ and why
__________ __________ How do you __________ ______ the diet
__________ Have __ store Yes pet’s
your ______ __________ ______ t was change
Where is your __________
there been food? __________
No ______ __ ______
pet housed? __________
any change ______ d.
Indoors __ s ____________________ Yes __________ ______ ______________ ______
Do you have Outdoors in urinatio No ______ ______ ____________
other pets? Diet Both __________n? __________ ______ ______ ____ _
Yes __________ __________ ______
and specify if No If so, please Yes __________ ____________ ______
__ ______ ____________
they live indoors For each list species __________ No __________ ______ ______ ______
or outdoors. of the __________ __________ ______ ______
__________ cable) and followin __________ ____________ __ ______ __________________
g categor __________ __________ ______ ______ _____
Drs. Byron L. Blagburn and
__________ often each amounts of all
__________ foods __________
ies, list __________
the brand ______________________
__ ______ ______
__________ food __ your pet names (if __________ ______ ______ _____
__________ __________ is fed (e.g., twice
Comme eats ____________________Are you
daily, as appli- __________ ______
__ ______ ______
rcial foods a day). open
__________ to making ______ ______
__________ __ well as __________ change ______
______ how a __ ______
__________ __________ Activity Yes
safe sedation of fractious febrile cats.
__________ ______ __ No in your ______
__________ __________ ____________ pet’s diet?
______ How active What are ?
__________ __________________ ____________ is your pet? your pet’s
______ ______ ______ food prefere
Feeding Manageme __________________ ____________ Hyperactive __________
Very active ______
______ ______ ______ ______
nt ______ ______ ______ Average ______ ______
Who typically ______ ______ Not very active ____ ______
______ ______ _____
______ ______ Hardly moves
Dwight D. Bowman present
feeds your pet? ______ ______ How ______ ______ ______ ______ ______
This downloadable form can
__________ ______ often is your pet ______
______ ______ _____
__________ ______ ________ ______ walked? ______ ______
__________ Comme ______ ______ What foods ______ ______
rcial treats; ______ At least 3 times/day __________ does your ______ _____
dental hygiene ______ 1-2 times/day pet ______
__ ______ ______
When is your
______ __________ products Seldom ______
Never ____ ______Once a day refuse? ______ ______
pet fed? __________ ______ ______ ______
______ ______ __ Do ______ ______ ______
______ __________ ______ you have access to a ______
______ __________ _
__________ ______ ____ ______ yard? ______ ______ ______
__________ ______ ______ ______
Is it difﬁcult ______ Yes ______ ______
______ __________ ____________ to exercise your ______ ______ No ______ ____
__________ ______ ____ pet? Are ______ ______
__________ ______ ______ __ Can exercise______ there foods ______ ______
______ __________ ____________ ______
be increased? Yes No ______ ____
__________ ______ ____ to which ______
current data and personal
__________ ______ Has your____________ If so, your _______
______ __________ ____________ pet participated in training? which foods? ____
Yes No pet is allergic? ____
________ Has your____________
pet participated ______
______Yes ______ Yes
______ ______ No ______ No
be given to clients to gather
in competition ______
______ ______ ? ______ ______
______ ______ Yes ______ ______
____ ______ No ______
______ ______ ______
______ ______ ____
______ ______ __
______ ____ _
CE ARTICLES experience to demonstrate
important information about their pet’s diet
h i t’ di t the importance of preventing
❯❯ The Renin–Angiotensin–Aldosterone parasitic infections and re-
NEWS BITES lated disease in companion
System: Approaches to Cardiac and
❯❯ What Makes Ticks Tick?
❯❯ Melanie Otte and Alan Spier ❯❯ Laparoscopic
Studies of tick salivary glands may reduce OVH and OVE
The renin–angiotensin–aldosterone system incidence of Lyme disease.
(RAAS) plays a signiﬁcant role in preserv-
ing hemodynamic stability in response to ❯❯ Compendium Board Member Talks to
the loss of blood volume, salt, and water. ABC News About Feline Cancer
Manipulation of the RAAS is the mainstay of Gregory K. Ogilvie is interviewed about a cancer
therapy for cardiac and renal diseases. diagnosis for Socks the cat.
❯❯ Lead and Zinc Intoxication ❯❯ Winn Foundation Announces Grants
in Companion Birds for Feline Health Studies
❯❯ Birgit Puschner and Robert H. Poppenga ❯❯ “Workaholic” Dolphins are Spongers
Although the toxicity of lead and zinc to ❯❯ AVMA Calls for More Veterinary
birds is widely recognized by veterinarians Oversight of Meat Production
❯❯ COMPENDIUM EXTRA Our
monthly e-newsletter service Four videos from Dr. Philipp
provides Web Exclusive articles Mayhew demonstrate some
and news, as well as a preview of of the techniques described
this month’s journal. Sign up at in the August 2008 Surgical
CompendiumVet.com. Views article by Dr. Sara
Gower and Dr. Mayhew,
“Canine Laparoscopic and
CONTACT US Ovariohysterectomy and
❯❯ Email your questions,
or letters to the editor:
Behavior Behavior Assessment:
The First Appointment*
About This Column ❯❯ Sharon L. Crowell-Davis, DVM, PhD, DACVB,a The University of Georgia
Behavior problems are a signiﬁ-
*The ﬁrst article in this series on patient evaluation, “Behavior Assessment: History Forms
cant cause of death (euthanasia)
and Interviews,” was published in the December 2008 issue of Compendium and is avail-
in companion animals. While most
able at CompendiumVet.com.
veterinary practices are necessarily
geared toward the medical aspect
of care, there are many opportuni-
ties to bring behavior awareness
A s described in the ﬁrst article in this series, gaining an accurate descrip-
tion of a pet’s undesirable behavior is crucial to correctly diagnosing the
cause of the behavior. However, more information is needed than a good
into the clinic for the beneﬁt of description. The circumstances in which the behavior occurs must also be
the pet, the owner, and ourselves. clariﬁed, along with any treatments the owner has already attempted, either
This column acknowledges the alone or with advice from a veterinarian, animal trainer, or other source. The
importance of behavior as part of pet’s signalment, environment, and background may all affect its behavior
and should be discussed with the owner. Some of this information can be
veterinary medicine and speaks
gathered in advance through the use of history forms; some may be better
practically about using it effectively
obtained through interviews and conversation with the owner during the ﬁrst
in daily practice. appointment devoted speciﬁcally to the behavior problem.
History of the Behavior
One of the most important pieces of information to gather is the current fre-
quency and intensity of the undesirable behavior. Without this information as a
baseline, it will be impossible to determine if a treatment is helping, harming, or
having no effect. The speciﬁc circumstances in which the problem behavior is
most likely to occur must also be ascertained. In some cases, it may be possible
to avoid these situations; in others, the treatment protocol may need to include
desensitization and counterconditioning to the speciﬁc circumstances.
Dr. Crowell-Davis discloses that she has received ﬁnancial support from CEVA Animal Health.
All behaviors that
the owner perceives
to be problem
behaviors need to
8 CompendiumVet.com | January 2009
11. The history of the behavior is also important. How after administering it for just 1 week, the medication
long has the animal been exhibiting this behavior? did not have time to take effect.
While there are exceptions, it is often the case that
problems of long duration will take longer to resolve Other Behavior Problems
than problems of short duration. This is especially The animal may have other behavior problems in
true of behaviors that have developed as a conse- addition to the chief complaint. Sometimes these
quence of operant conditioning, such as persistently problems come up in the discussion of the chief
waking the owners during the night, because the complaint, but not always. Before proceeding to
undesirable behavior has been reinforced hundreds issues other than the animal’s presenting
or even thousands of times, rather than a few dozen behavior, ask if the owner has noticed QuickNotes
times. Also, in attempts to treat the problem, the any other behavior problems that have
owners may have reinforced the undesirable behav- not been mentioned yet. Occasionally,
The duration, fre-
ior on a variable-ratio or variable-interval schedule it turns out that the owner considers a quency, intensity,
by trying to ignore the behavior for a while but even- problem other than the presenting com- and context of the
tually acknowledging it. If this is the case, the behav- plaint to be of more concern but had problem behav-
ior will have become very resistant to extinction. not previously mentioned it because ior need to be
he or she believes it to be untreatable. identiﬁed.
History of Treatment For example, a dog may be aggressive,
Another critical piece of the history is how the own- but the owner has brought it in for storm phobia
ers have already attempted to correct the behavior. because of a recent news story about treatments
There is a tremendous amount of information about for storm phobia.
animal behavior on the Internet. Some is excellent. If the animal has multiple behavior problems,
Some is mediocre. Some is unclear or confusing, and it may be necessary to prioritize treatments. It is
some will actually make behavior problems worse. rare that the treatments for multiple problems are
Clients are likely to have tried various treatment pro- mutually exclusive. More typically, there are simply
tocols they have found on the Internet or in books. limitations to how much time and effort a client can
As with terms describing behaviors, this is a poten- put into treating a pet’s behavior problems. Thus, if
tial area of misunderstanding. Just because a client a dog has fear aggression toward men, moderate
knows the word desensitization does not mean that storm phobia, mild separation anxiety, and a nui-
the Web site or book where he or she read about it sance habit of jumping up on women as a form of
described it accurately or that the client understood friendly greeting, and the client can spend approxi-
the description correctly. Even if the original resource mately 20 minutes a day conducting speciﬁc behav-
is accurate, the client may have conducted the pro- ior modiﬁcation, it will be impossible to address all
tocol improperly and attempted a different treatment, these problems at once. It therefore makes sense to
such as ﬂooding, instead. Thus, if a client says that prioritize them in the order presented.
he or she has already tried “treatment X,” ask for an
exact, detailed description of what he or she did. Owner Commitment
In some cases, the client has identiﬁed the cor- For some owners, the amount of time and effort
rect behavior modiﬁcation treatment and conducted necessary to treat one problem, let alone several,
it appropriately, and it is helping, but not enough. In is daunting. Therefore, one of the most important
this circumstance, conﬁrm that the treatment should pieces of information to obtain at the ﬁrst appoint-
be continued. However, it will be necessary to build ment, in addition to a complete
on the current protocol, perhaps with a new variation description of any problem behav- TO LEARN
of the established behavior modiﬁcation plan or with ior, is a full understanding of how MORE
medication. In other cases, the treatment may be a motivated the owner is to treat the
reasonable option, and the client may be conducting problem and keep the pet. At one
it accurately, but it is having no effect. In these cases, end of the spectrum are owners For more information about
an entirely different approach is needed. who intend to keep the pet, regard- clarifying the correct terms
If medications prescribed by other veterinar- less of the success of treatment. At in conversations with
owners, see the December
ians have not been effective, verify the medication, the other end are those who intend
2008 article “Behavior
the dose, and how long it was given to determine to euthanize or give away the pet
Assessment: History Forms
whether it was genuinely not beneﬁcial or was sim- if resolution of the behavior prob- and Interviews” at
ply not given at an adequate dose for an adequate lem is not quick and easy. If the CompendiumVet.com.
time. For example, if a client discontinued ﬂuoxetine owners are considering giving the
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 9
pet away, it is important to in which the pet lives. The
apprise them of the difﬁcul- - Previously attempted treat- same information should
ties of ﬁnding an alternative be gathered for all the
home for a pet with a major r ments need to be identi- other pets in the household.
behavior problem. This is ﬁed. It is important to Finally, ask for a complete
especially the case with description of the pet’s phys-
aggressive pets. Sometimes verify that these treatments ical environment, including
owners think the police or r the house and yard. How
armed forces will want their r
were carried out correctly big is the house? Are there
aggressive dog as a guard and appropriately. The parts of the house in which
dog. However, for guard and the pet is not allowed? Is the
attack work, police and mili- - fact that someone knows yard fenced in, and does the
tary organizations want only y a word characteristic of fencing adequately contain
dogs that are trained to attack the pet? Is the pet walked on
in a specific way at a spe- - the jargon of learning and a leash? If so, how often and
ciﬁc command. They do not for how long? What is the
want dogs that have behavior r
behavior modiﬁcation neighborhood like? Is there
problems and are likely to does not mean that he or a problem with encoun-
inﬂ ict bites because of such tering other pets while on
issues as fear. she knows how to conduct walks? Are pedestrians and
Beyond the extremes of f the treatment correctly. cars rare, common, or con-
willingness to keep a pet or r stant? Does this vary with
intent to give it up, there is the time of day?
the question of how much time and effort an owner Certain aspects of the environment may be iden-
can and will put into treating a pet. Major behavior tiﬁed as contributing to the existence and exacer-
problems typically require daily effort by the owner bation of the problem. For example, if the pet is
during a period of weeks or months. Even if the nervous and timid, living in the midst of boister-
owner is highly motivated to do whatever it takes, ous young children may make improvement difﬁcult
it is essential for the owner and the veterinarian to unless a mechanism can be identiﬁed to give the pet
take a realistic look at the owner’s current schedule time away from the children in a quiet, calm atmo-
and lifestyle. If the owner can realistically identify sphere. Aspects of the environment that can be used
only three times a week in which he or she can to help the pet, or that need to be changed for the
do structured behavior modiﬁcation for 20 minutes, pet, can also be identiﬁed. If a healthy young dog
it is important to set up a treatment program that is getting inadequate exercise because no one has
assumes only three treatment sessions a week. If the time to take it on long walks or jogs, the addition
treatment plan assumes that the owner will conduct of fencing in the backyard may be critical. In some
behavior modiﬁcation every day and this is simply cases, the owners may have already been consider-
not possible, then the owner and the pet are on ing a change (e.g., a fence). The news that making
track for failure from the beginning. the change is likely to help their pet may be all that
is needed to get them to follow through.
Owner lifestyle is only one aspect of the context in Signalment
which the pet’s behavior problem exists. To prop- Signalment is a basic
erly identify and treat the problem, it is important to information set that TO LEARN
understand all the aspects of the pet’s environment, veterinarians are MORE
both social and physical. The social environment already accustomed
includes the people and animals with which the pet to collecting. As with
regularly interacts. All the humans who either live many medical con- For more information about
in the same household as the pet or visit frequently, ditions, signalment cognitive dysfunction, see
the February 2008 article
either as guests or employees (e.g., gardener, maid), often gives us infor-
“Cognitive Dysfunction in
need to be identiﬁed. In addition to their names, mation about the Senior Pets” at
sexes, and ages, their relationship and interactions relative likelihood CompendiumVet.com.
with the pet are critical to understanding the world of a given behav-
10 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
13. ior problem. In cases of older pets presenting with with treatment. Dogs and cats that were born and
behavior problems, it is essential to identify whether raised in puppy or kitten mills where they received
the current problem is actually of recent onset. little to no socialization with humans may be exces-
Sometimes owners have tolerated a given behavior sively shy around humans and susceptible to devel-
problem in a pet for years, but changes in the fam- oping a variety of anxiety disorders as
ily circumstances, rather than any substantial changes a consequence of their early experience. QuickNotes
in the pet, have made the problem less tolerable. If Extra effort will be required to help them
the problem is of recent onset, or if there has been overcome these problems. Likewise, pets
a signiﬁcant change in the intensity or frequency of that have spent time as strays, fending for assist in prioritiz-
the problem in an older pet, cognitive dysfunction, themselves to survive, may have become ing the differential
analogous to Alzheimer disease, should be consid- very aggressive around food, especially diagnosis.
ered. However, cognitive dysfunction should not be if their ability to obtain food while stray
considered as a possible diagnosis in a young animal. was not very successful and they became under-
If the complaint is aggression in a dog, aggressively weight. Owners who find problem behaviors very
“herding” people or other animals should be a diag- frustrating are often more tolerant of them if they
nostic differential for herding breeds, but it is unlikely understand why their pet behaves in an undesir-
in nonherding breeds. able fashion.
If possible, ﬁnd out about the early history of
the pet. Sometimes this is not possible because the Conclusion
owners adopted the pet at several months to several The third article in this series will complete the
years of age. However, if background information discussion of the history that needs to be reviewed
is available, it can be useful in helping the owners at the first visit and address direct assessment of
understand the problem, even if it does not help the patient.
Particularly intriguing or difﬁcult cases
Case Presentation #1
❯❯ Karen A. Moriello, DVM, DACVD, University of Wisconsin-Madison
A 7-month-old dog presented with
“bumps,” a common clinical presenta-
TO LEARN MORE
tion of superﬁcial bacterial pyoderma
in dogs. Note the “goose bumps” or
hive-like lesions on the skin. Clinical Snapshot presents illustrated
1. What is the name of this condition, case histories and challenges you to
and what is seen upon close examina- answer the questions posed. This case
tion of the skin? is part of the series of Self-Assessment
Colour Review books on multiple topics
2. What are the diagnostic differentials,
from Manson Publishing Ltd., London,
and what diagnostic tests should be
available from Blackwell Publishing
conducted to conﬁrm the diagnosis? Professional.
3. What is the mechanism of action of
ﬂuoroquinolone antibiotics, and why For more information or to obtain any of the
would this drug class not be an appro- books in the series, call 800-862-6657
priate antibiotic choice in this dog? or visit BlackwellProfessional.com
SEE PAGE 21 FOR ANSWERS AND EXPLANATIONS.
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 11
COLOSTRUM IN THE DIET
FOR CANINE INTESTINAL HEALTH AND IMMUNE SYSTEM SUPPORT
Arleigh Reynolds, DVM, PhD, DACVN COLOSTRUM BENEFITS SHOWN
Ebenezer Satyaraj, PhD Research shows dietary colostrum may beneﬁt growing
While veterinarians have long recognized the connection puppies and adult dogs. Weaned puppies fed a bovine
between colostrum and enhanced immunity in newborns, colostrum–supplemented diet for 10 days after arrival at
recent research shows dogs of all ages can beneﬁt from pet stores had signiﬁcantly improved fecal quality compared
colostrum’s supportive effects on gastrointestinal (GI) health. to the control group.4 In a 40-week study, bovine colostrum
was fed to adult Alaskan sled dogs under exercise stress.5
The ﬁndings demonstrate that, while colostral antibodies Compared to controls, colostrum-supplemented dogs had:
are not absorbed by older puppies and adult dogs as in 1- or
2-day-old pups, the immunoglobulin-rich substance contains • Increased intestinal microﬂora diversity,5 which reduces
elements that support proper GI tract development, nutrient the risk of bacterial pathogens colonizing the GI tract.6
absorption, growth and healthy intestinal microﬂora.1 • More stable microbial populations following stress, which
GI TRACT KEY TO IMMUNE FUNCTION helps reduce risk of diarrhea and GI upset.5
The GI tract plays a vital role in protecting the body • Increased fecal IgA levels, indicating improved GI mucosal
from pathogens. With gut-associated lymphoid tissue immune status.5
(GALT), the intestinal tract is the body’s largest • Greater, persistent antibody levels following canine
immune organ.2,3 distemper virus (CDV) vaccination, suggesting enhanced
The intestinal mucosa provides a protective barrier and systemic immune status. The immune systems of
secretes immunoglobulin A (IgA), which helps neutralize colostrum-supplemented dogs were not hyperactive, based
potential pathogens and stabilize intestinal microﬂora. on normal C-reactive protein levels. 5
Measure of microﬂora stability
0 * <0.05
During stress, dogs fed a colostrum-supplemented
diet had more stable gut microflora.
1. Edwards, Christine. Interactions between nutrition and the intestinal microflora.
GI TRACT KEY TO IMMUNE FUNCTION Proc Nutr Soc. 1993;52(2):375–82.
2. Hall EJ. Mucosal immunity—Why it’s important [Internet]. In: The 32nd Congress of the
(1) Immunoglobulin (Ig) binds to an immune cell in the GI mucosa. World Small Animal Veterinary Association Proceedings Online; 2007 Aug 19–23; Sydney,
(2) Ig binding activates the immune cell. Australia. Available at: http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA
2007&PID=18137&Print=2986&O=Generic. Accessed April 25, 2008.
(3) Cytokines are secreted into the circulatory system, enabling 3. Tizard IR. Immunity at body surfaces. In: Tizard IR, ed. Veterinary Immunology: An
communication with other immune cells. Introduction. 7th ed. Philadelphia, Pa: Saunders; 2004:234–246.
(4a) Activated systemic immune cells release IgG into the 4. Giffard CJ, Seino MM, Markwell PJ, Bektash RM. Bene ts of bovine colostrum on fecal
quality in recently weaned puppies. J Nutr. 2004;134:2126S–2127S.
circulatory system in response to immune system challenges. 5. Data on le, 2006. Nestlé Purina PetCare Company.
(4b) Mucosal immune cells release IgA into the GI tract lumen, 6. Kuehl CJ, Wood HD, Marsh TL, et al. Colonization of the cecal mucosa by
Helicobacter hepaticus impacts the diversity of the indigenous microbiota. Infect Immun.
leading to increased levels of fecal IgA. 2005;73:6952–6961.
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16. 3 CE
CREDITS CE Article 1
The Diagnostic Approach to Fever
of Unknown Origin in Dogs*
❯❯ Julie Flood, DVM, DACVIM Abstract: Identifying the cause of a fever of unknown origin (FUO) in dogs presents a consider-
Antech Diagnostics able diagnostic challenge. The diagnostic workup can be frustrating for veterinarians and clients,
especially when it fails to reach a ﬁnal diagnosis after extensive testing. Fortunately, most causes
of FUO can be found or treated successfully. This article discusses FUO in dogs and provides
information about common causes, the diagnostic approach, and potential treatments.
rue fever (pyrexia) is deﬁned as an serum biochemistry proﬁle, and urinaly-
increase in body temperature due to sis with antimicrobial culture. The cause
an elevation of the thermal set point of fever in most dogs is an infection that
in the anterior hypothalamus secondary to either is found during the initial workup or
the release of pyrogens.1 With hyperther- responds to antibiotic treatment; therefore,
mic conditions other than true fever, the most dogs do not have a true FUO.5
hypothalamic set point is not adjusted.1
At a Glance Nonfebrile hyperthermia occurs when heat Differential Diagnosis
Differential Diagnosis gain exceeds heat loss, such as with inade- The differential diagnosis for FUO in dogs
Page 14 quate heat dissipation, exercise, and patho- is extensive, and development of an algo-
Clinical Approach logic or pharmacologic causes.1 rithm covering all causes is not feasible.
Page 14 Dogs with true fever typically have body Some causes of FUO in dogs are listed
Potential Causes of Fever temperatures between 103°F and 106°F in BOX 1.2,4,5 Most FUOs are caused by a
of Unknown Origin in Dogs (39.5°C to 41.1°C).2 Prolonged body tem- common disease presenting in an obscure
Page 15 peratures above 106°F are dangerous and fashion.6
can result in organ failure, disseminated Current information in the veterinary
Approach to Fever of intravascular coagulation, systemic inﬂam- literature regarding FUO in dogs is lim-
Unknown Origin in Dogs matory response syndrome, and death.1,3 ited.1,5 Infectious, immune-mediated, and
Page 16 Such temperatures are usually seen with neoplastic diseases are all important and
nonfebrile causes of hyperthermia rather common causes.2,5,7,8 About 10% to 15%
than with true fever.4 Temperatures less of FUOs in dogs remain undiagnosed
than 106°F are unlikely to be harmful and despite thorough diagnostic evaluation.5
may be beneﬁcial because they constitute The prognosis for undiagnosed FUO in
a protective response to inﬂammation.1,5 dogs is not known. However, a retrospec-
The term fever of unknown origin (FUO) tive study7 revealed that in 13 of 14 dogs
is used liberally in veterinary medicine.5 with undiagnosed FUO, the fever either
It should be used to identify a fever that resolved spontaneously or responded to
does not resolve spontaneously, that does antibiotics, NSAIDs, or corticosteroids.
not respond to antibiotic treatment, and
for which the diagnosis remains uncer- Clinical Approach
WEB tain after an initial diagnostic workup.5 The diagnostic approach must be tailored
EXCLUSIVE Along with a thorough history and physi- to the patient. It should be guided by his-
cal examination, initial diagnostics should tory and physical examination ﬁndings,
Supplemental material to this
include a complete blood count (CBC), simple laboratory testing, and the poten-
article is available at tial causes common to the geographic
CompendiumVet.com. *A companion article about fever of unknown location.9,10 A three-stage approach, such as
origin in cats begins on page 26. the one presented in BOX 2, is commonly
14 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
The Diagnostic Approach to FUO in Dogs CE
used.2,4,5 Communication with the owner is or subtle clinical signs (historical, intermit-
of utmost importance to ensure understand- tent, and current) because these may help
ing of the time and ﬁnancial commitment that localize the fever source. A history of stiffness
may be required to obtain a deﬁnitive diagno- may suggest joint disease, but fevers can pres-
sis. Fortunately, a diagnosis can be obtained ent similarly.3 Often, diagnostic clues are not
in most circumstances, and many causes are readily apparent on physical examination, so
treatable or manageable.8 repeated detailed physical examinations are
All medications should be discontinued to essential (by multiple clinicians, if possible).10
help rule out a drug-induced fever. If the fever Careful attention should be paid to the whole
persists beyond 72 hours after medication cessa- body—pulses, skin, mucous membranes, oral
tion, a drug reaction can be ruled out.11 cavity, lymph nodes, heart, abdomen, bones
and joints, and rectum. Repeated fundic and
History and Physical Examination neurologic examinations are also important to
Obtaining a thorough history is the ﬁrst step identify subtle changes. As the disease pro-
of a successful diagnostic approach. Clients gresses, new clues may emerge to help guide
should be questioned carefully about speciﬁc the next diagnostic steps.
Complete Blood Count and Serum
Potential Causes of Fever Biochemistry Profile
of Unknown Origin in Dogs2,5 CBC and serum biochemistry proﬁle abnor-
malities in dogs with FUO are generally non-
Bacterial infection (focal or systemic): Bacter- speciﬁc, but they may indicate a need for
emia, infective endocarditis, septic arthritis, further diagnostic tests. Every CBC should
osteomyelitis, diskospondylitis, septic meningi- be accompanied by a blood smear evaluation
tis, pyothorax, pyelonephritis, prostatitis, stump to detect morphologic changes and parasites.
pyometra, peritonitis, deep pyoderma, abscess Frequently, multiple blood smears and care-
Bacterial diseases: Brucellosis, bartonello- ful scanning are necessary to ﬁnd infectious
sis, borreliosis, leptospirosis, mycoplasmo- organisms (FIGURE 1). Sometimes only one
sis (hemotrophic and nonhemotrophic), tu- organism will be seen on an entire slide. It
berculosis and other mycobacterial diseases, is wise to save serum for serologic testing or QuickNotes
diseases caused by L-form bacteria (e.g., cel- other special tests that may be crucial in the
lulitis, synovitis) future. A serum bile acids assay may be indi-
Urine culture should
Viral: Canine distemper, parvovirus
cated because fever may be the only predomi- be conducted for all
Rickettsial: Ehrlichiosis, anaplasmosis, Rocky dogs with fever of
nant clinical sign in dogs with portosystemic
Mountain spotted fever, salmon poisoning
shunts.12 unknown origin.
Fungal: Histoplasmosis, blastomycosis,
Protozoal: Toxoplasmosis, neosporosis, Urinalysis with Culture
babesiosis, trypanosomiasis, hepatozoonosis, A urine sample obtained via cystocentesis
leishmaniasis (unless contraindicated) should be submitted
Immune-mediated diseases: Immune-
mediated hemolytic anemia, polyarthritis,
systemic lupus erythematosus, rheumatoid
arthritis, vasculitis, meningitis, steroid-
responsive neutropenia and fever
Neoplastic: Lymphoma, leukemia, multiple
Courtesy of Dr.Ty McSherry
myeloma, malignant histiocytosis, necrotic
Noninfectious inﬂammatory diseases: Lym-
phadenitis, panniculitis, pansteatitis, panos-
teitis, pancreatitis, granulomatosis
Miscellaneous: Portosystemic shunt, drug
reaction, toxin, shar-pei fever, metabolic bone
disorders, idiopathic causes HISTOPLASMA ORGANISMS found on a blood
smear from a dog.
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 15
CE The Diagnostic Approach to FUO in Dogs
for a complete urinalysis with bacterial cul-
Staged Diagnostic Approach to Fever ture even if sediment is inactive. These tests
of Unknown Origin in Dogs2,4 should be repeated, especially if there is a his-
tory of lower urinary tract disease, as a nega-
Stage 1 tive urine culture does not rule out infection.
Take a thorough history. Further diagnostic testing could include urine
Stop all medications to rule out drug-induced fever. protein:creatinine ratio if proteinuria is pres-
Perform a meticulous physical examination, including fundic and
ent with inactive sediment.
Obtain samples for CBC, blood smear, and serum chemistry proﬁle.
Save serum for serology or other testing.
Two-view abdominal and three-view thoracic
Obtain a urine sample for complete urinalysis and urine culture.
radiographs should be obtained if the mini-
Submit a sample for urine protein:creatinine ratio if proteinuria and
inactive sediment are present. mum database does not reveal the cause of the
Conduct fecal centrifugation and fecal cytology, if indicated. fever. Total body radiographs can help aid in
Consider obtaining thoracic and abdominal radiographs. the diagnosis of masses, pneumonia, pyotho-
Consider trial antibiotics if bacterial infection is suspected (e.g., rax, or other infections. Joint radiographs can
doxycycline if ehrlichiosis is suspected). aid in the diagnosis of an erosive immune-
If necessary, proceed to stage 2. mediated polyarthritis.3 Other anatomic areas
to radiograph include long bones (especially in
Stage 2 young dogs), the spine, and dental structures
Repeat stage 1 tests as indicated. (tooth root abscesses, masses). Special contrast
Obtain thoracic and abdominal radiographs if not obtained in stage 1. radiographic studies can focus on other body
Conduct abdominal and other ultrasonography as indicated. systems (urogenital, spinal, gastrointestinal).
Conduct echocardiography if a heart murmur is present.
Conduct heartworm testing, if indicated. Ultrasonography
Conduct ﬁne-needle aspiration with cytology of masses, lymph Abdominal ultrasonography allows for evalu-
nodes, and ﬂuids (cyst, pleural, peritoneal, prostatic wash), if ation of organ parenchyma and can detect
indicated. lesions not apparent on survey radiographs.
Conduct blood culture. It can also assist with ﬁne-needle aspiration
Conduct arthrocentesis. or biopsy if needed. Thoracic ultrasonogra-
Conduct fecal cultures, if indicated. phy can be conducted if abnormalities (e.g.,
Conduct bone marrow aspiration if warranted by CBC results. pleural effusion, cysts, masses) are detected
Conduct serology for infectious diseases. on radiographs. When thoracic disease is
Obtain long bone and joint radiographs.
not radiographically evident, ultrasonography
Conduct protein electrophoresis, if indicated.
is not rewarding because the lungs obscure
Conduct an immune panel, if indicated.
intrathoracic anatomy.13 Ultrasonography can
If necessary, proceed to stage 3.
also be used to evaluate ocular (including
Stage 3 retrobulbar), ventral cervical (thyroid/parathy-
Repeat stage 1 and 2 tests as indicated. roid, lymph node, salivary gland), and muscu-
Conduct echocardiography even if no murmur is present. loskeletal (skin, subcutaneous, joint, muscle)
Conduct transesophageal echocardiography. regions if indicated.14–16
Conduct bone marrow aspiration even if CBC results are normal.
Perform biopsy as indicated. Echocardiography
Conduct bronchoscopy and bronchoalveolar lavage as indicated. Echocardiography should be conducted in
Conduct cerebrospinal ﬂuid analysis. dogs with FUO and a heart murmur, especially
Conduct dental radiography. a new or diastolic murmur. Vegetative lesions
Consider computed tomography, magnetic resonance imaging, must be differentiated from proliferative myx-
nuclear imaging, or positron emission tomography. omatous valve degeneration. Dogs with infec-
Conduct laparoscopy or thoracoscopy as indicated. tive endocarditis are usually medium to large
Consider exploratory celiotomy. breeds that do not tend to have myxomatous
Administer trial antibiotic or antifungal therapy. valve degeneration.17 Echocardiography can
CBC = complete blood count
also be used to evaluate for a heart base mass
if one is clinically suspected.
16 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
The Diagnostic Approach to FUO in Dogs CE
Blood Culture FIGURE 2
Blood cultures should be conducted (prefera-
bly during a pyrexic episode) for all dogs with
FUO, especially those with a heart murmur,
bounding pulses, lameness (polyarthritis),
Courtesy of Dr.Ty McSherry
back pain (diskospondylitis), or urinary tract
infection, as the latter three conditions can be
sequelae to endocarditis.17 It is common for
dogs with positive blood cultures to have iso-
lation of the same organism from other tissue
or ﬂuid sites (cardiac, urinary, spinal).18 Aseptic
techniques for obtaining samples are described
elsewhere.2,19,20 The volume of the blood sam- MORULAE in macrophages in a splenic aspirate from a dog infected with
ple is more important than the timing; larger Ehrlichia canis.
volumes are associated with an increased diag-
nostic yield in human medicine.19,21,22 Patient FIGURE 3
size determines the amount of blood to be
drawn. As a general guideline, 16 to 20 mL of
blood should be obtained from large dogs,
and 5 mL of blood should be obtained from
Courtesy of Dr.Ty McSherry
cats and small dogs.2 The blood should be
divided evenly and placed aseptically into aer-
obic and anaerobic blood culture vials (~70-mL
vials for large patients, and ~20-mL vials for
small patients).2 If the patient’s size allows, a
second blood sample can be obtained immedi-
ately from a different site and divided as
described above.2 If the dog has recently FINE-NEEDLE ASPIRATE from a spleen in a dog with malignant histiocytosis.
received antibiotics, blood culture vials with
resins that bind antibiotics should be used.2,19 planum, skin, feces) can also be conducted if
Evidence suggests that recovery is improved in indicated. Fluid samples should be submitted
samples from blood culture resin vials because for bacterial culture if the sample quantity is
the resins may absorb inhibitors other than anti- sufﬁcient.
biotics23; therefore, use of these vials for all
blood samples may be warranted. Bartonella Bone Marrow Evaluation
spp are emerging as an important cause of Bone marrow aspiration should be conducted
culture-negative infective endocarditis in dogs; early in the evaluation of dogs with FUO if CBC
therefore, submission of samples for Bartonella abnormalities consistent with bone marrow Arthrocentesis can
polymerase chain reaction (PCR) testing as disease are present. It should be considered in yield critical diag-
well as serology is recommended in suspected later diagnostic stages if no deﬁnitive diagno-
cases.24 Blood culture PCR techniques are sis has been made, even if the CBC is normal,
being used in human medicine and may be because neoplasia and infectious diseases can
for many dogs with
valuable for use in dogs for detecting other be common causes of FUO in dogs.2,8 fever of unknown
infections in the future.25 origin.
Cytologic Examination Immune-mediated polyarthritis is a common
Fine-needle aspiration with cytology should cause of FUO in dogs even when no signs of
be conducted on any suspicious masses or arthritis are present (FIGURE 4).7,8 Arthrocentesis
lymph nodes, ﬂuid accumulations, or abnor- should be conducted on several joints and the
mal organs. Cytology can be rewarding in samples submitted for cytologic evaluation
the diagnosis of many infections as well (EDTA microcontainer) and possibly bacterial
as in the identiﬁcation of abnormal cells culture (aerobic, anaerobic, and mycoplasma).
(FIGURES 2 AND 3). Impression cytology (nasal Infectious arthropathy needs to be ruled out
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 17
CE The Diagnostic Approach to FUO in Dogs
FIGURE 4 exposure (e.g., fungal disease, most rickettsial
diseases) or previous infection (e.g., protozoal
disease) and does not necessarily correlate with
active disease or current clinical signs.28
Immunodiagnostic Screening Panels
Immunodiagnostic panels (antinuclear anti-
body, rheumatoid factor, Coombs) are typically
Courtesy of Dr.Ty McSherry
unrewarding in dogs with FUO for several
reasons, including the potential for false-pos-
itive results.2,7,8 Antiplatelet antibody tests and
serum protein electrophoresis can be con-
ducted if thrombocytopenia or hyperglobu-
linemia, respectively, is present.
JOINT FLUID from the tarsus of a dog with
immune-mediated polyarthritis. Other Diagnostic Tests
Other diagnostic tests, such as prostatic wash,
if suppurative inﬂammation is seen on cytol- cerebrospinal ﬂuid analysis, and bronchos-
ogy because samples from septic joints do not copy with bronchoalveolar lavage, should be
always contain degenerate neutrophils, and a considered if clinical abnormalities suggest
negative joint culture does not rule out infec- prostatic, neurologic, or respiratory disorders,
tion.26 If only a small sample can be obtained, respectively. Samples should be submitted for
it should be used for direct cytology. Otherwise, cytologic evaluation as well as aerobic and
it is recommended to submit synovial ﬂuid sam- anaerobic bacterial culture if quantity permits.
ples in blood culture medium to improve the Bronchoalveolar lavage samples should also
diagnostic yield.26 Synovial membrane biopsy be submitted for mycoplasma and slow-grow-
with culture can also be considered.26 Bacterial ing fungal cultures.
endocarditis can cause true infective arthritis
or immune-mediated arthritis, and the two Advanced Imaging
conditions must be differentiated.27 Immune- Computed tomography (CT) and magnetic res-
mediated polyarthritis tends to involve the onance imaging (MRI) should be used to help
carpi and tarsi, whereas infective arthritis fre- delineate diagnosed conditions or when the
quently involves larger joints (e.g., stiﬂe, elbow, diagnosis remains equivocal.10 Nuclear scintig-
shoulder).27 If immune-mediated polyarthritis is raphy is being used more frequently in vet-
suspected, serology for rickettsial disease and a erinary medicine to detect infections and may
heartworm test may be indicated.27 be a valuable tool in the investigation of FUO
in dogs.29 Another promising imaging modal-
Serology ity being used in human medicine, called
Serum samples should be submitted for fungal image fusion, is the combination of positron
and rickettsial disease testing if these diseases emission tomography (PET; a type of nuclear
are clinically suspected and if patient history imaging) and CT. A few reports of the use
indicates possible exposure. These tests should of image fusion in dogs demonstrate that this
not be used as screening procedures in the technique could play an important role in
hope that something abnormal will be found. investigating canine FUO.30–33
Because Toxoplasma and Neospora spp are
ubiquitous protozoal parasites, paired serum Biopsy
TO LEARN MORE
antibody titers for IgG and IgM should be sub- If ﬁne-needle aspiration cytology cannot pro-
For more information on mitted if a diagnosis continues to be elusive. A vide a deﬁnitive diagnosis, a biopsy may be
special tests that can be
single high IgM indicates active or recent infec- helpful. In one study,7 biopsy samples submit-
used in diagnosing the
cause of FUO in dogs, tion, and a fourfold IgG rising titer conﬁrms ted for histopathology enabled a diagnosis in
please visit the Web infection.28 It is important to remember that a 15 of 17 dogs with FUO. Tissue samples can
Exclusives section of negative antibody titer does not rule out infec- be obtained percutaneously (with or without
tion and that a single positive titer implies either imaging assistance); via endoscopy, laparos-
18 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
The Diagnostic Approach to FUO in Dogs CE
copy, or thoracoscopy; or surgically during trial antifungal agents may be of use.
laparotomy. Submission of tissue samples for If the fever does not respond to antibiotics or
histopathology and possibly bacterial or fun- antifungals, options include waiting to see if new
gal cultures is recommended. Exploratory diagnostic clues arise and considering an immu-
celiotomy with biopsy is indicated only by the nosuppressive trial of corticosteroids. A dramatic
results of diagnostic testing.8 The diagnostic improvement should be expected within 24 to
yield of exploratory celiotomy in a dog with 48 hours of corticosteroid therapy in dogs with
no indication for surgery is unknown. an immune-mediated FUO.2,5 It is important to
inform owners about the risks of trial corticos-
Treatment teroids, such as allowing a fungal or bacterial
Speciﬁc treatment is based on the deﬁnitive infection to disseminate or further decreasing the
diagnosis, if found. Administering intravenous chance to diagnose the problem, as with lym-
ﬂuids or placing a fan blowing toward the cage phoma. Ideally, during a corticosteroid trial, the
can be used to reduce the temperature in hos- dog should be hospitalized and monitored closely
pitalized patients. In dogs for which extensive for adverse effects.5 Initial improvement does not
investigation yields no diagnosis, judicious use equal successful treatment. One study7 revealed
of antibiotic therapy may be warranted. The that treatment 24 hours before referral was associ-
choice of antibiotic depends on the suspected ated with a statistically signiﬁcant increase in the
bacterial agent. If no response is seen after 72 time to diagnosis. Therefore, it is suggested that,
hours with appropriate dosing, another antibi- when possible, therapy be withheld or withdrawn
otic that covers a different spectrum may be in dogs referred for investigation of FUO.
chosen.34 If a bacterial infection is suspected
in a severely ill patient, the four-quadrant Conclusion
approach—choosing an antibiotic or combi- The most common and important causes of
nation of antibiotics that is effective against FUO in dogs are infection, immune-mediated
aerobic, anaerobic, gram-positive, and gram- disease, and cancer. Using a logical diagnostic
negative organisms—is recommended.34 If anti- approach to FUO in dogs usually results in a
biotic therapy is not successful, NSAIDs can be deﬁnitive diagnosis. Sometimes, being patient QuickNotes
administered, keeping in mind the potential and allowing new diagnostic clues to emerge
The most common
side effects.5,7 Fever can result in considerable by revamping historical information (via reas-
malaise, dehydration, and anorexia; therefore, sessing current information and possibly and important
clinicians must decide in each case whether obtaining a more detailed history) and repeat- causes of FUO in
NSAIDs could be beneﬁcial.4 Antipyretics (e.g., ing physical examinations and simple labora- dogs are infection,
ketoprofen, ﬂunixin meglumine, dipyrone) tory tests is more desirable than proceeding immune-mediated
should be used with caution because fever can with more invasive and expensive tests if the disease, and cancer.
be beneﬁcial, and many argue that antipyretic dog is stable. Communicating with the client
therapy can have a negative impact on the is of utmost importance. A broad knowledge
body by causing hypothermia and impairing of the possible causative diseases and the abil-
the host’s immune defenses.4,5,35 Fevers may ity to interpret speciﬁc diagnostic test results
increase the bactericidal effect of antibiotics in the context of FUO in dogs are essential to
and serum and can also decrease the pathoge- diagnose the source of an FUO.
nicity of some pathogens.4,5,35 If an antipyretic
is considered necessary, aspirin can be admin- The author thanks Leo “Ty” McSherry, DVM, DACVP,
istered at a dosage of 10 mg/kg q12h PO.2 If clinical pathologist at Antech Diagnostics in Irvine,
there is clinical suspicion of a fungal disease, California, for the cytology images.
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er SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. fever of unknown origin. Vet Med 2000;95(8):633-642.
Vol 1. 6th ed. St. Louis: Elsevier Saunders; 2005:9-13. 5. Couto CG. Fever of undetermined origin. In: Nelson RW, Couto
2. Lunn KF. Fever of unknown origin: a systematic approach to CG, eds. Small Animal Internal Medicine. 4th ed. St. Louis: Elsevier;
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1995;17:470-481. cats. J Small Anim Pract 1987;28:167-181.
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19. Haggstrom J, Kvart C, Pedersen HD. Acquired valvular heart Vet Radiol Ultrasound 2006;47(2):228-233.
disease. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary 33. LeBlanc AK, Jakoby B, Townsend DW, et al. Thoracic and ab-
Internal Medicine. Vol 2. 6th ed. St. Louis: Elsevier Saunders; dominal organ uptake of 2-deoxy-2-[18F]ﬂuoro-D-glucose (18FDG)
2005:1022-1039. with positron emission tomography in the normal dog. Vet Radiol
20. Calvert CA, Wall M. Cardiovascular infections. In: Greene CE, Ultrasound 2008;49(2):182-188.
ed. Infectious Diseases of the Dog and Cat. 3rd ed. St. Louis: El- 34. Lappin MR. Practical antimicrobial chemotherapy. In: Nelson
sevier Saunders; 2006:841-865. RW, Couto CG, eds. Small Animal Internal Medicine. 4th ed. St.
21. Li J, Plorde JJ, Carlson LG. Effects of volume and periodicity on Louis: Elsevier; 2009:1291-1301.
blood cultures. J Clin Microbiol 1994;32(11):2829-2831. 35. Klein NC, Cunha BA. Treatment of fever. Infect Dis Clin North
22. Karchmer A. Infective endocarditis. In: Braunwald E, ed. Heart Am 1996;10(1):211-216.
CREDITS CE TEST 1 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 CompendiumVet.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 statement regarding the investi- 2. What is the correct deﬁnition of a true 3. Which statement regarding fever in dogs
gation of FUO in dogs is false? fever? is true?
a. Two-view abdominal and three-view a. increase in body temperature due to an a. The cause of fever in most dogs is
thoracic radiographs are recommended. elevation of the thermal set point in the neoplasia.
b. Joint radiographs can aid in the diag- anterior hypothalamus b. Most FUOs in dogs are caused by a
nosis of an erosive immune-based b. increase in body temperature due to an common disease presenting in an
polyarthritis. elevation of the thermal set point in the obscure fashion.
c. Thoracic ultrasonography should anterior pituitary gland c. Dogs with true fevers commonly
always be conducted, especially if c. a marked, rapid rise in body tempera- have prolonged body temperatures
abnormalities are not detected on tho- ture without adjustment of the thermal above 106°F.
racic radiographs. set point in the anterior hypothalamus d. Prolonged body temperatures
d. Dogs with infective endocarditis are d. a marked, rapid rise in body tempera- above 106°F are not dangerous.
usually medium to large breeds that ture without adjustment of the
do not tend to have myxomatous valve thermal set point in the anterior
degeneration. pituitary gland
20 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
The Diagnostic Approach to FUO in Dogs CE
4. FUO in dogs is commonly the result 7. Which statement regarding blood cul- 9. Which statement is true with regard to
of ____________ disease. tures for dogs with FUO is false? dogs with FUO?
a. infectious a. Blood cultures can be conducted for a a. Antibiotics should never be started
b. neoplastic dog currently on antibiotics. unless the deﬁnitive cause of FUO is
c immune-mediated b. It is rare for dogs with positive blood determined.
d. all of the above cultures to have isolation of the same b. A negative fungal antibody titer rules
organism from other sites. out infection with that organism.
5. Which statement regarding sample c. Obtaining a larger blood sample c. Initial improvement after the start
culture is true? volume is more important than of corticosteroids does not equate
a. A negative urine culture can rule the timing of the sample. to successful treatment because
out pyelonephritis. d. Bartonella spp are emerging as many diseases can respond favorably
b. A negative blood culture can rule an important cause of culture-negative initially.
out bacteremia. infective endocarditis in dogs. d. Bone marrow aspiration is only indi-
c. A negative joint culture can rule out cated if the CBC is abnormal.
septic arthritis. 8. Which statement regarding arthrocente-
d. none of the above sis in the evaluation of a dog with FUO is 10. Which statement is false with regard to
true? dogs with FUO?
6. When evaluating a dog with FUO, a. Only one joint should be tapped a. Using a logical approach usually results
a. it is usually not necessary to evaluate to decrease the chance of septic in a deﬁnitive diagnosis.
a blood smear in conjunction with contamination. b. It is important to run as many diagnos-
the CBC. b. Immune-mediated polyarthropathies tic tests as quickly as possible when
b. a urine culture is only indicated tend to involve larger joints such as the evaluating a stable dog with FUO.
when there is an active urine stiﬂes, elbows, and shoulders. c. Conduct fecal centrifugation and fecal
sediment. c. Degenerate neutrophils are not always cytology, if indicated.
c. repeated neurologic and fundic exami- seen with septic joints. d. If fever persists beyond 72 hours
nations are important. d. Immune-mediated polyarthritis is after a medication has been discontin-
d. a joint tap is recommended only for extremely rare in asymptomatic dogs ued, a drug-induced fever can be
dogs presenting with lameness. with FUO. ruled out.
Answers and Explanations Case Presentation #1
SEE PAGE 11 FOR CASE PRESENTATION. common differentials include pem- warm weather, can occur in approx-
1. This is an example phigus, sterile eosinophilic pus- imately 50% of patients.
of superﬁcial bacte- tulosis, and pustular demodicosis. 3. Fluoroquinolone antibiotics prevent
rial infection of the However, bacterial folliculitis is most bacterial DNA synthesis by partly
skin involving the commonly confused with dermato- inhibiting bacterial DNA gyrase.
hair follicles, hence phytosis or urticaria. Demodicosis, This class of drugs is primarily
the name superﬁcial concurrent Malassezia infection, active against gram-negative aero-
bacterial folliculitis. and other infections should be bic and facultative anaerobic bac-
Close examination ruled out by skin scrapings, impres- teria. Although they are effective
of the skin reveals small papules at sion smears, and dermatophyte cul- against many gram-positive organ-
the base of the hairs. These papules/ tures, respectively. isms (e.g., staphylococci), the mini-
pustules may rupture, causing the The diagnosis of a bacterial pyo- mum inhibitory concentrations are
formation of tiny epidermal collar- derma is often a clinical diagnosis usually higher than for gram-nega-
ettes, which may be seen encircling supported by ruling out demodi- tive bacteria. Fluoroquinolone anti-
the base of the hairs. cosis and dermatophytosis, the biotics are contraindicated in this
2. The major diagnostic differentials two most common follicular dis- particular patient because they are
are dermatophytosis, demodico- eases. Concurrent bacterial and known to cause erosive arthropathy
sis, and Malassezia dermatitis. Less Malassezia infections, especially in in young dogs.
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 21
24. Using a Diet History
to Improve Adherence to
❯❯ Kathryn E. Michel, DVM, MS, DACVN,* University of Pennsylvania
Proper dietary management is essential to pet health, yet changing pet owners’ feeding practices is often
difﬁcult. Taking a diet history provides an opportunity to open a dialogue about animals’ dietary needs as
well as invaluable information that will aid in tailoring speciﬁc dietary interventions to the needs and prefer-
ences of patients and their caregivers.
ommunicating effectively with people the household? Do any of them spend all day
C about the nutrition and dietary manage- with the pet? Inquire whether there are other
ment of their pets can be difﬁcult, par- pets in the home and whether they are—or
ticularly when the goal is to persuade them to can be—fed separately from the patient. Can
alter their feeding practices. However, circum- the patient get into the other pets’ food? Ask
stances frequently arise in which a change in whether the pet is conﬁned indoors or is
feeding management may be in the best inter- allowed outside. If the pet is allowed out, is
ests of a pet. Obtaining a complete diet history is it supervised while it is outside? Does it have
the essential ﬁrst step in the process of altering the opportunity to steal food, get into garbage,
feeding practices to suit a pet’s needs. The diet scavenge, or hunt?
history provides information about what the pet
is being fed and whether this food is complete, The Principal Diet, Feeding Routines,
balanced, and appropriate to the pet’s life stage and Eating Behaviors
QuickNotes and health status. Just as important, the history Obtain the precise names (including ﬂavor, if
provides information about how food is used appropriate) and brands of all commercial pet
Information from in interactions between the pet and the other foods that the patient is receiving and the spe-
the diet history is members of the household. Understanding this ciﬁc amounts fed. Often, caregivers cannot pro-
essential for deter- relationship is a key element when designing vide this information accurately by recall alone
mining whether a dietary interventions that meet the health and and need to check labels and measure feeding
patient is receiving nutritional needs of the patient and are accept- portions. Also, pet owners who use a scoop to
an appropriate and able to the pet’s caregivers. measure dry food often do not realize the true
adequate diet. size of their measuring device. If the pet is eat-
Elements of the Diet History ing a canned diet, ask what size can the owner
A complete diet history gives an accurate account buys. Some varieties of pet food are sold in
of all foods fed to a pet on a typical day. It is an multiple can sizes (e.g., 5.5 and 12 oz), so the
opportunity to evaluate all the ways that food size used by the client is important informa-
is involved in interactions between the pet and tion. Make sure to ask whether the food the pet
the other members of its household. It should is currently eating is its usual diet and, if not,
also be an opportunity for the pet’s caregivers when the diet change was implemented.
to offer their viewpoints regarding the propo- If the pet is eating a commercial pet food,
sition of modifying their feeding practices. ask if the diet is being supplemented with any
*Dr. Michel discloses that human foods. If this is the case, it is important
she has received ﬁnancial
support from Nestlé
The Household to get accurate details, including measured
Purina PetCare Company Begin by asking about who lives with the amounts of all foods routinely given to the
and Royal Canin. pet. How many adults and children are in pet. If the pet is being fed a home-prepared
22 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
25. CONTRIBUTED BY
THE AMERICAN COLLEGE OF
diet, ask for the recipe, including measured consider such items treats, and many of the Founded in 1988, the primary
amounts of all the ingredients. Some owners products and foods used for these purposes objective of the American College
do not use a standard recipe when making a are high in calories. of Veterinary Nutrition (ACVN) is
home-prepared diet. It is useful to ask these It is important to remember to inquire to advance the specialty area of
owners to keep a diary of all food fed to the pet whether the pet routinely receives any supple- veterinary nutrition and increase
the competence of those who
for 5 to 7 days. Be certain to inquire whether ments or medications that are disguised with
practice in this ﬁeld by establish-
the pet is receiving any dietary supplements. food. Human foods that are typically used to ing requirements for certiﬁcation
If possible, have the client bring in the supple- pill a dog or cat, such as cheese, lunch meats, in veterinary nutrition, encour-
ments—or at least the label information—so or peanut butter, are often high in sodium, fat, aging continuing professional
you can see exactly which nutrients are being and calories. For example, one study evalu- education, promoting research,
supplemented and in what quantities. ating dogs with cardiac disease showed that and enhancing the dissemination
Ask about the daily routine of feeding the 62% of the owners used human or pet food of new knowledge of veterinary
nutrition through didactic teaching
pet. Is the pet fed at certain times of the day, for pill administration and that many of these
and postgraduate programs.
or is food always available? If the pet is fed foods were high-sodium table foods such as
with other pets, are the meals supervised? cheese or lunch meats.1 For more information, contact:
Does one person assume responsibility for One further point to ask about is the pet’s American College of Veterinary
feeding the pet, or can it vary day-to-day? This level of activity and opportunity to exercise. Is Nutrition, c/o Dawn Cauthen,
is important information, especially when you the pet walked regularly? How often, and how Administrative Assistant,
are making dietary recommendations, because far? Find out whether the pet goes outside, School of Veterinary Medicine:
Dept. of Molecular Biosciences
the person who brings the pet to the ofﬁce may has a fenced-in yard—and if so, how large—
One Shields Avenue
not be the person who will be implementing or participates in regular activities that involve
Davis, California 95616-8741
the new plan. Ask about how and where the exercise, such as going to a dog park or an
food is stored (e.g., in a sealed container, in agility class. See if you can gauge whether Telephone: 530-752-1059
the refrigerator). If the pet is fed a dry food, is increasing the opportunity to exercise would
the food bought in large quantities, and how be feasible in the household. This information
long does it take to use up a bag of food? Food is especially valuable when you are designing
can lose its freshness over time, especially if it a weight reduction program for a patient.
is not stored under optimal conditions.
Inquire about the pet’s normal feeding Gathering the Information
behavior. Is the pet an “easy keeper” or a picky This may seem like a great deal of information
eater? Does the pet eat the food as soon as it to gather in a routine ofﬁce visit, but the pro-
is offered, or is it content to graze through- cess can be expedited by having a diet history
out the day? Does the pet usually eat all the form available for clients to ﬁll out while they
food that is offered? Does the pet beg for food are in the waiting room. As previously men-
between meals? If the pet is not eating as it tioned, the client may not be able to recall all
normally does, ﬁnd out what has changed and of the information in the ofﬁce and may need
for how long the behavior has been altered. to take the form home. If your practice has a
Web site, you can have a link to a download-
Treats, Supplements, and Exercise able version of the form so that clients can
When inquiring about treats, ask the question ﬁll it out before the ofﬁce
several times in different ways. Ask speciﬁcally visit. To help expedite the
about which commercial treats are used—not process, a veterinary techni-
just the brand name but also the ﬂavor, variety, cian familiar with taking diet
and size. Ask about human foods and table histories can either gather
scraps. Ask about products or foods that are the pertinent information Photocopy the diet history form
used to promote chewing and dental hygiene directly from a client during on pages 47 and 48 for your clients,
or to alleviate boredom. Also inquire about the visit or review the diet or download a customizable PDF
different ways food may be used as a reward, history form for complete- of the same form from
such as for performing tricks or for good ness and accuracy once the CompendiumVet.com.
behavior during walks. Owners do not always client has ﬁlled it out.
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 23
26. Negotiating a Diet Change
The information obtained in the diet history HEALTHY BITES
will be invaluable for making appropriate and,
hopefully, acceptable dietary recommendations To get an accurate account of
for your patients. Knowing a pet’s current diet the foods fed to a pet on a
and any recent changes to it will inform your
decision about what kind of dietary modiﬁca-
tion may be necessary to address the pet’s health Find out if you are speaking to the person
condition and what kind of diet the pet may ﬁnd responsible for feeding the pet.
most acceptable. Being aware of owner prefer- Have a diet history form available that the
ences and potential obstacles to change will help client can take home so he or she can check
you tailor your recommendations not only to the the labels and measure the amounts of food
pet but also to the entire household to ensure that the pet is fed (see pages 47 and 48 or
the greatest probability of success and adherence. CompendiumVet.com for a sample diet
Understanding the client’s attitude toward, and history form).
concerns about, the dietary management of pet Request that dry pet foods be measured
dogs and cats will present you with the oppor- with an 8-oz kitchen measuring cup.
tunity to open a dialogue with the client about Ask speciﬁcally about the different treats
pet nutrition and educate him or her about the
and supplemental foods a pet might receive
(e.g., commercial treats, table foods and
QuickNotes reasons for your recommendations.
scraps, oral hygiene products, foods used as
Investigations in human medicine have
Making an effort found that when physicians make an effort
rewards, foods used for administering pills,
to talk with pet dietary supplements).
to talk with patients about their knowledge,
owners about their beliefs, concerns, and expectations about
beliefs, concerns, their condition, the result is better adherence Conclusion
and expectations to treatment regimens.2 Exploration of all of The information that can be obtained from a
can result in bet- these issues from a patient’s perspective on diet history can greatly facilitate the process
ter adherence to his or her illness permits the attending health of implementing dietary therapy for a patient.
professional to address deﬁciencies in knowl- It can help not only in making an appropri-
edge or understanding of the condition and its ate diet selection and accurate feeding recom-
treatment and the patient’s ability and willing- mendations but also in understanding the pet
ness to pursue a particular course of therapy. owner’s rationale for current feeding practices
In veterinary medicine, the owner speaks for and assessing any concerns that may arise
the patient, but the same principle applies. from a diet change. By anticipating problems,
With regard to dietary practices, despite a you should be able to craft the dietary inter-
basic uniformity in nutritional requirements vention in a way that will be acceptable to the
and physiologic needs, there is considerable pet’s household or, at the very least, to com-
variation in what humans eat. In the case of pet municate more effectively with the pet owner
dogs and cats, their owners largely determine about the rationale for the changes in feeding
what they eat on a daily basis. Yet in many, management. You will be in a better position
if not most, cases, client education alone will to explain why you feel the changes you are
not succeed in changing habits and behaviors proposing are in the pet’s best interest and to
relating to how a pet is fed. Just as a person’s look for compromise when your recommen-
social and cultural context will inﬂuence his dations and the pet owner’s preferences are
or her own dietary habits, it will also have an in conﬂict.
impact on how and what that person feeds
a pet. Therefore, it is important to consider References
the social and cultural aspects of owners’ food 1. Freeman LM, Rush JE, Markwell PJ. Dietary patterns of dogs
with cardiac disease. J Nutr 2002;132:1632S-1633S.
consumption in order to communicate effec-
2. The “why”: a rationale for communication skills teaching and
tively with them about their pets’ nutritional learning. In: Kurtz S, Silverman J, Draper J. Teaching and Learning
needs and appropriate dietary management, Communication Skills in Medicine. 2nd ed. San Francisco: Radcliffe
particularly if you are attempting to change 3. Michel KE. Unconventional diets for dogs and cats. Vet Clin
current feeding practices.3 North Am Small Anim Pract 2006;36:1269-1281.
24 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
The Curious Case of
the Cat with the Munchies
We found the article “Five Common Toxins
Ingested by Dogs and Cats” extremely in-
teresting and practical. We recently treated
a 5-month-old domestic shorthaired cat for CE Article #1
Five Common Toxins Ingested
marijuana toxicity following ingestion of a by Dogs and Cats
Julie Ann Luiz, DVM
“hash brownie.” The cat presented with per- University of Hawaii at Hilo
Johanna Heseltine, DVM, MS, DACVIM
Oklahoma State University
plexing sudden-onset neurologic signs and ABSTRACT: Substances that are toxic to pets are present in most households. Early identification of
intoxication is crucial to preventing or minimizing gastrointestinal absorption of toxins.The history,
clinical signs, and laboratory test results can be used to make a presumptive diagnosis and begin therapy.
hypothermia (temperature 94.5°F [34.7°C]). O
nce absorbed from the gastrointestinal
(GI) tract, many toxins lack a specific
antidote and are associated with severe
systemic effects that are difficult to treat.
in veterinary medicine are derived from the
human medical literature. Decontamination and
treatment strategies for the toxins discussed in
this article are summarized in Table 1.
Therefore, prompt decontamination is the first
With gentle coaxing, the owners admitted step in managing patients that have ingested
toxic materials. If the toxin ingested is known,
therapy should be initiated before clinical signs
develop. This article discusses the general prin-
If the owner suspects toxicosis and calls the
clinic before presenting the animal, the veteri-
narian must consider the risks and benefits
ciples for minimizing GI absorption of ingested of instructing the owner to administer an
the source of the problem. (The brownie had toxins and the clinical presentation and man-
agement of toxicosis caused by five commonly
ingested household substances: anticoagulant
rodenticides, ethylene glycol (EG), marijuana,
emetic.1 Productive emesis requires the pres-
ence of food or liquid in the stomach, espe-
cially for retrieval of small volumes of toxin.2
Removal of the poison from the stomach is
chocolate, and metaldehyde. most effective within 1 hour of ingestion, is
been carefully wrapped in plastic ﬁlm and
useful up to 2 hours after ingestion, and is of
DECONTAMINATION STRATEGIES limited benefit more than 4 hours after inges-
FOR ORALLY INGESTED TOXINS tion.2,3 Early emesis may remove up to 80% of
GI decontamination techniques are used to pre- the ingested material.3
vent or limit the absorption of ingested toxins. Induction of emesis is contraindicated for
Because many toxins lack a specific antidote, corrosive and caustic materials, as well as for
hidden but had disappeared while the patient • Take CE tests
decreasing the amount of
toxin absorbed may be life -
saving, and decontamination
strategies should begin as soon
petroleum distillates and other volatile materials
that may result in aspiration pneumonia. 2,3
Vomiting should not be induced in patients
that are depressed or have decreased conscious-
• See full-text articles as possible after ingestion of a ness or those that have seizures or are likely to
was alone in the house. Clawed plastic and CompendiumVet.com
toxic substance. Most decont-
amination methods practiced
seizure.2,3 Emetics should not be administered if
the patient has already vomited.2
COMPENDIUM 578 November 2008
crumbs were found at the scene.)
At the time, we found little informa- Drs. Luiz and Heseltine mentioned are rare and—when they do occur—
tion in the literature speciﬁcally on drug testing as a means of conﬁrming carry a good prognosis. Nonetheless, we
cases of feline marijuana ingestion. To the diagnosis. We did not do this at the encourage colleagues treating known or
our knowledge (and anecdotally), mari- outset due to the client’s ﬁnancial con- strongly suspected cases of marijuana
juana toxicity in cats is more likely to straints. When we undertook a detailed toxicity to submit samples for toxicol-
occur via inhalation when owners blow literature search and realized so little ogy screening and to share their data.
smoke in the cat’s face, rather than via was known about feline toxicity due to Drs. Anne Fawcett
dietary indiscretion, as is more com- Cannabis sativa, we offered to cover and Angela Phillips
mon in dogs. In this case, we did not the cost of toxicology testing. The own- Sydney Animal Hospitals Inner West
ascertain the ingested dose and did not ers allowed us to collect a urine sample Stanmore, NSW
know how long the patient would take from the patient via cystocentesis; how- Australia
to recover. ever, the sample, collected 14 days after
Hypothermia persisted for approxi- ingestion, returned a negative result.
mately 24 hours. One of the signs not THC may be detectable in human urine DO YOU HAVE
mentioned in the article by Drs. Luiz samples for 4 to 6 weeks, but the time
SOMETHING TO SAY?
and Heseltine was marked polyphagia. frame in which it remains detectable
During hospitalization, our patient ate in samples from companion animal Send your letters, suggestions,
ravenously. At one point, the patient species is not known, according to the comments, or questions to
defecated, passing a piece of a shoelace. pathologist at the laboratory to which E-MAIL editor@
This may have been ingested as a result we submitted the sample (Dr. Bruce CompendiumVet.com
of the cat’s marijuana-enhanced appetite Duff at Symbion Vetnostics). The recom- FAX 800-556-3288
before hospitalization, suggesting that mended time frame for submission of
gastrointestinal foreign bodies are a samples is within 48 hours of exposure
Veterinary Learning Systems
potential side effect of marijuana toxic- to the toxin.
780 Township Line Road,
ity (as is chocolate toxicity, if marijuana In this case, we are conﬁdent the
Yardley, PA 19067
is ingested in a brownie). The patient patient was suffering from marijuana
was discharged 3 days later when the toxicity. The negative urinalysis result More letters are online at
neurologic signs resolved, although the may be due to the fact that a young, CompendiumVet.com
owner reported that the cat had a “lazy lean cat can metabolize marijuana rela-
eye” for 2 weeks after discharge. tively rapidly. Fortunately, these cases
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 25
28. 3 CE
CREDITS CE Article 2
The Diagnostic Approach to Fever
of Unknown Origin in Cats*
❯❯ Julie Flood, DVM, DACVIM Abstract: Identifying the cause of fever of unknown origin (FUO) in cats is a diagnostic challenge,
Antech Diagnostics just as it is in dogs. Infection is the most common cause of FUO in cats. As in dogs, the diagnostic
workup can be frustrating, but most FUO causes can eventually be determined. This article address-
es the potential diagnostic tests for, and the differential diagnosis and treatment of, FUO in cats.
rue fever (pyrexia) is deﬁned as an during the initial workup or responds to
increase in body temperature due to antibiotic treatment; therefore, most cats
an elevation of the thermal set point do not have a true FUO.4
in the anterior hypothalamus secondary to
the release of pyrogens.1 With hyperther- Differential Diagnosis
mic conditions other than true fever, the Information regarding FUO in cats is
hypothalamic set point is not adjusted.1 extremely limited, and there are no retro-
At a Glance Nonfebrile hyperthermia occurs when heat spective studies. Fevers are common in cats,
gain exceeds heat loss, such as with inade- and most diseases associated with FUO
Differential Diagnosis quate heat dissipation, exercise, and patho- in cats are infectious.5 Neoplasia is a less
Page 26 logic or pharmacologic causes.1 common cause of FUO in cats, and FUO
Clinical Approach Cats with true fever typically have body due to immune-mediated disease is rare in
Page 26 temperatures between 103°F and 106°F cats.6 FUO causes are often separated into
Potential Causes of Fever (39.5°C to 41.1°C).2 Cats are less likely than groups based on the underlying disease
of Unknown Origin in Cats dogs to succumb to the dangerous effects mechanism.2,3,7 Most FUOs are caused by a
Page 27 of body temperatures greater than 106°F, common disease presenting in an obscure
which are usually seen with nonfebrile fashion.8 BOX 1 lists some causes of FUO in
Approach to Fever of causes of hyperthermia.3 Temperatures cats. It is thought that about 10% to 15% of
Unknown Origin in Cats less than 106°F are unlikely to be harm- FUOs in cats remain undiagnosed despite
Page 28 ful in cats and may be somewhat beneﬁ- thorough diagnostic evaluation.4
cial because they constitute a protective
response to inﬂammation.1,4 Clinical Approach
The term fever of unknown origin (FUO) As in dogs, the diagnostic approach to FUO
is used liberally in veterinary medicine. It in cats must be targeted to each patient. It
should be used to identify a fever that does should be guided by history and physi-
not resolve spontaneously, that does not cal examination ﬁndings, laboratory test
respond to treatment with antibiotics, and results, and the potential causes common
for which the diagnosis remains uncertain to the geographic location.9,10 A three-
after an initial diagnostic workup.4 Along stage approach, such as the one presented
with a thorough history and physical in BOX 2, is commonly used.2–4 The goal of
examination, initial diagnostics include investigating an FUO is to promptly estab-
WEB a complete blood count (CBC), an FeLV lish a deﬁnitive diagnosis while minimiz-
EXCLUSIVE antigen test, an FIV antibody test, a serum ing patient discomfort, client expense,
biochemistry proﬁle, and urinalysis with
antimicrobial culture. The cause of fever aFor more information on the clinical ap-
Supplemental material to this in most cats is infection that either is found proach to cats with FUO, please refer to the
article is available at clinical approach section in the article starting
CompendiumVet.com. *A companion article about fever of unknown on page 14. Many of the same tests used in
origin in dogs begins on page 14. dogs can also be used in cats.
26 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
The Diagnostic Approach to FUO in Cats CE
and invasive diagnostic tests.2 Communication History and Physical Examination
with the owner is of utmost importance to Obtaining a thorough history is the ﬁrst step
ensure understanding of the time and ﬁnan- to a successful diagnostic approach. The vac-
cial commitment that may be required in order cination history should be ascertained because
to obtain a deﬁnitive diagnosis. vaccines can cause immune-mediated fevers
If possible, all medications should be dis- in cats during the immediate postvaccination
continued early in the evaluation to help rule period, and modiﬁed live virus vaccines can
out a drug-induced fever. If the fever persists induce local lymphoid replication of the atten-
beyond 72 hours after cessation of the medi- uated agent.5,12 Determining indoor/outdoor
cation, a drug reaction can be ruled out.11 status, travel history, ﬂea and tick control and
Drugs that are known to induce fever in cats potential exposure to diseases transmitted by
include tetracycline, sulfonamides, penicillins, parasites (e.g., hemotrophic mycoplasmosis,
and levamisole. ehrlichiosis, bartonellosis, cytauxzoonosis),
and contact with other cats is also impor-
BOX 1 tant as many FUO causes are transmissable.5
Knowledge of ingestion of prey species may
Potential Causes of Fever
be helpful because songbirds can carry sal-
of Unknown Origin in Cats2,4 monellosis, rabbits can carry tularemia, and
rodents can carry plague or toxoplasmosis.5
Bacterial infection (focal or systemic): Bac- Cats are frequently affected by stress hyper-
teremia, infective endocarditis, septic arthritis,
thermia, which must be ruled out before an
osteomyelitis, diskospondylitis, septic menin-
extensive diagnostic evaluation is pursued. As
gitis, pyothorax, pyelonephritis, prostatitis,
in dogs, FUO diagnostic clues in cats are gen-
stump pyometra, peritonitis, abscess
Bacterial diseases: Bartonellosis, borrelio- erally not readily apparent on physical exami-
sis(?), mycoplasmosis (hemotrophic and non- nation, so repeated detailed examinations are
hemotrophic), tuberculosis and other myco- essential.9 The whole body should be carefully
bacterial diseases, diseases caused by L-form palpated to detect subtle swelling or discom-
bacteria (e.g., cellulitis or synovitis secondary fort, which may help localize the fever source.
to bite wounds or surgical incisions) The thorax should be gently compressed
Viral: FeLV, FIV, feline infectious peritonitis, to evaluate for a cranial mediastinal mass.
feline calicivirusa Repeated fundic examination should be per-
Rickettsial: Feline ehrlichiosis, anaplasmosis, formed because numerous infectious diseases QuickNotes
Rocky Mountain spotted fever (e.g., FIP, FIV, FeLV) cause ocular changes.
Fungal: Histoplasmosis, blastomycosis, cryp- Absence of ocular changes does not rule out
tococcosis, coccidioidomycosis infection with these diseases. Repeated neu- are the most com-
Protozoal infections: Toxoplasmosis, cytaux- rologic and orthopedic examinations should mon causes of
zoonosis, neosporosis(?), babesiosis(?), try- be performed, although they can be difﬁcult fever and fever of
panosomiasis(?) to interpret in an uncooperative cat. unknown origin in
Immune-mediated diseases: Polyarthritis,
systemic lupus erythematosus, rheumatoid
Feline Leukemia and Feline
arthritis, vasculitis, meningitis, steroid-re-
sponsive neutropenia and fever
FeLV antigen and FIV antibody blood tests
Neoplastic: Lymphoma, leukemia, multiple
should be conducted on every febrile cat.
myeloma, necrotic solid tumors
Noninfectious inﬂammatory diseases: These tests are rapid and reliable, but it is
Lymphadenitis, panniculitis, pansteatitis, important to understand how to interpret posi-
pancreatitis, granulomatosis tive results.13,14
Miscellaneous: Portosystemic shunt, drug
reaction, toxin, hyperthyroidism, idiopathic Fecal Examinations
causes Fecal samples should be obtained from cats
with FUO. If diarrhea is discovered, rectal
Hurley KE, Pesavento PA, Pedersen NC, et al. An cytology should also be conducted. Other
outbreak of virulent systemic feline calicivirus dis- diagnostic tests to consider include fecal ﬂota-
ease. JAVMA 2004;224(2):241-249.
tion with centrifugation, direct fecal examina-
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 27
CE The Diagnostic Approach to FUO in Cats
tion, and fecal cultures. Cats can be bacteremic
Staged Diagnostic Approach to Fever from Salmonella (and possibly Campylobacter)
of Unknown Origin in Cats2,3 infection without diarrhea, so fecal cultures
should be submitted, especially if neutrophils
Stage 1 are evident on rectal cytology.15-17 If clostridial
Take a thorough history. spores are seen on cytology, samples should
Stop all medications to rule out drug-induced fever. be submitted for Clostridium perfringens
Perform a meticulous physical examination, including
fundic and neurologic examinations.
Conduct FeLV and FIV testing.
CBC and Serum Biochemistry Profile
Obtain samples for CBC, blood smear, and serum
Typically, the changes seen on the CBC and
Save serum for serology or other testing. serum chemistry proﬁle in cats with FUO are
Conduct a complete urinalysis and urine culture. nonspeciﬁc but can help suggest the next diag-
Submit a sample for urine protein:creatinine ratio if nostic steps. A blood smear should always be
proteinuria and inactive sediment are present. evaluated along with the CBC to help identify
Conduct fecal centrifugation and fecal cytology, if indicated. morphologic changes, infectious organisms, or
Consider obtaining thoracic and abdominal radiographs. changes consistent with neoplasia. Serum should
Consider trial antibiotics if bacterial infection is suspected be saved at this point for future testing, if needed.
(e.g., doxycycline if ehrlichiosis is suspected). Recently, a cat with nonspeciﬁc signs and a fever
If necessary, proceed to stage 2. was diagnosed with a portosystemic shunt, so a
serum bile acids assay should be considered.18
Repeat stage 1 tests as indicated. Urinalysis with Culture
Obtain thoracic and abdominal radiographs if not obtained A urine sample collected by cystocentesis (unless
in stage 1. contraindicated) should be submitted for urinaly-
Conduct abdominal and other ultrasonography as indicated. sis with antimicrobial culture and sensitivity for
Conduct echocardiography if a heart murmur is present. every cat with FUO, regardless of the appear-
Perform ﬁne-needle aspiration with cytology of masses,
ance of the urine. If the cat has a history of lower
lymph nodes, and ﬂuids (cyst, pleural, peritoneal).
urinary tract disease, urine should be submitted
Conduct blood culture.
for urinalysis and culture and sensitivity on mul-
tiple occasions because a negative urine culture
Conduct fecal cultures, if indicated.
Conduct bone marrow aspiration if warranted by CBC results. does not rule out infection. A sample should be
Conduct serology for infectious diseases. submitted for urine protein:creatinine ratio if pro-
Obtain long bone and joint radiographs. teinuria is present with inactive sediment.
Conduct an immune panel, if indicated.
If necessary, proceed to stage 3. Cytology
Fine-needle aspiration should be conducted on any
Stage 3 suspicious masses, lymph nodes, ﬂuid accumula-
Repeat stage 1 and 2 tests as indicated. tions, or abnormal organs, and samples should
Conduct echocardiography even if no murmur is present. be submitted for cytology (FIGURE 1). Impression
Conduct transesophageal echocardiography. cytology (nasal planum, skin lesion, feces, rectal
Perform bone marrow aspiration even if CBC results mucosa) can also be conducted, if indicated.
Perform biopsy as indicated. Serology
Perform bronchoscopy and bronchoalveolar lavage Serum samples should be submitted for infec-
as indicated. tious disease testing (e.g., feline infectious
Conduct cerebrospinal ﬂuid analysis. peritonitis, bartonellosis, hemoplasmosis, rick-
Perform dental radiography.
ettsiosis, anaplasmosis) if a disease is clinically
Consider computed tomography, magnetic resonance im-
suspected and if patient history suggests pos-
aging, nuclear imaging, or positron emission tomography.
sible exposure. Toxoplasmosis serology (IgG
Perform laparoscopy or thoracoscopy as indicated.
Consider exploratory celiotomy. and IgM) should be submitted for all cats
Administer trial antibiotic or antifungal (if indicated) therapy. with FUO. Natural clinical infections in cats
with neosporosis have not been documented,
28 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
The Diagnostic Approach to FUO in Cats CE
so testing for this disease may not be war- FIGURE 1
ranted.19 Serology for feline foamy virus (pre-
viously known as feline syncytium-forming
virus) can be conducted for cats with FUO
and suspected joint disease.20
Courtesy of Dr.Ty McSherry
Blood culture should be conducted for cats
with FUO and suspected bacteremia. Typical
signs of bacteremia in cats include anorexia,
pyrex ia, and shi f ti ng leg lameness. 21,22
Vegetative endocarditis is uncommon in cats, HISTOPLASMA ORGANISMS found in a pulmo-
but these animals typically have heart mur- nary fine-needle aspirate from a cat. The organisms
murs.21,22 Underlying predisposing causes for are located predominately in the macrophages.
which patients should be evaluated include
pyothorax, septic peritonitis, gastrointestinal are all associated with polyarthritis in cats.24–27
tract disease, pneumonia, endocarditis, pyelo- Other infective arthritides include fungal, rick-
nephritis, osteomyelitis, pyometra, and bite ettsial, and protozoal diseases.28
wounds.21 In a recent study,23 bacteremia was
diagnosed in 66 cats over a 9-year period. Immunodiagnostic Screening Panels
Immune panels (antinuclear antibody, rheuma-
Radiography toid factor [RF], Coombs) are thought to be unre-
Two-view abdominal and three-view thoracic warding in cats with FUO, but in a recent study, QuickNotes
radiographs should be obtained if the mini- 10 of 12 cats deﬁnitively diagnosed with rheu-
Urine culture should
mum database does not reveal the cause of matoid arthritis were strongly seropositive for
the FUO. Cats with lower respiratory disease RF.2,8,29,30 Therefore, although RF is not speciﬁc
be conducted for
are frequently asymptomatic, so care must be for rheumatoid arthritis, it may be an important every cat with fever
taken to rule out primary or secondary respi- diagnostic test in cats. The study also stated that of unknown origin
ratory problems. four cats diagnosed with periosteal proliferative regardless of the
polyarthritis were negative for RF.30 Antiplatelet appearance of the
Ultrasonography antibody tests and serum protein electrophore- urine sediment.
Abdominal ultrasonography can be valuable sis can be conducted if thrombocytopenia or
in detecting lesions not seen on radiographs. hyperglobulinemia, respectively, is present.
It can also assist with ﬁne-needle aspiration
or biopsy if needed. Thoracic ultrasonogra- Other Diagnostic Testing
phy is not rewarding unless there are radio- Other diagnostic tests, such as cerebrospinal
graphic changes. ﬂuid analysis and bronchoscopy with broncho-
alveolar lavage or transtracheal wash, should
Bone Marrow Evaluation
Bone marrow aspiration should be performed FIGURE 2
early in the evaluation of cats with FUO if
CBC abnormalities consistent with bone mar-
row disease are present (FIGURE 2). It should
be considered later if no deﬁnitive diagnosis
Courtesy of Dr. Robin Allison
has been made, even if the CBC is normal,
because neoplasia and infectious disease can
cause FUO in cats.2
Arthrocentesis should be conducted on cats
even if there is no obvious evidence of joint dis-
ease. Calicivirus, mycoplasmosis, L-form bacte- HISTOPLASMA ORGANISMS in a bone marrow
rial infection, and FeLV with feline foamy virus aspirate from a cat.
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 29
CE The Diagnostic Approach to FUO in Cats
FIGURE 3 Fevers may increase the bactericidal effect of
antibiotics and serum and can also decrease
the pathogenicity of some pathogens.3,31 Fever
can result in considerable malaise, dehydration,
and anorexia; therefore, clinicians must decide
in each case whether NSAIDs could be beneﬁ-
cial.3 If an antipyretic is considered necessary,
Courtesy of Dr. Robin Allison
aspirin dosed at 10 mg/kg q48–72h PO can
be used.2,4 Empirical antibiotic therapy should
be based on the organ system involved or the
infectious agent suspected.5 Trial antifungal
therapy should be considered for cats with sus-
pected fungal infections that cannot be proven.
Trial corticosteroids can be considered in cats
TOXOPLASMA ORGANISMS in a bronchoal- with FUO for which the cause cannot be iden-
veolar lavage cytology sample from a cat. tiﬁed, making sure to discuss potential compli-
cations with the owner before use.
be considered if clinical abnormalities suggest
QuickNotes neurologic or respiratory disorders, respectively. Conclusion
Samples should be submitted for cytologic eval- Fevers are common in cats, and infectious
Repeated fundic uation and aerobic and anaerobic bacterial cul- disease is the most common cause of fever
examinations ture and sensitivity testing if quantity permits in cats. Using a logical diagnostic approach
are essential in (FIGURE 3). Bronchoalveolar lavage samples to a cat with an FUO will usually result in a
cats with fever of should also be submitted for mycoplasma and deﬁ nitive diagnosis. Sometimes, being patient
unknown origin. slow-growing fungal cultures. Advanced and allowing new diagnostic clues to emerge
imaging techniques and biopsy may be helpful by revamping historical information (via
in some cases, as in dogs. reassessing current information and possibly
obtaining a more detailed history) and repeat-
Treatmentb ing physical examinations and simple labora-
Speciﬁc treatment is based on the deﬁnitive tory tests is more desirable than proceeding
diagnosis, if found. A fan directed toward the with more invasive and expensive tests if the
cat’s cage or administration of intravenous ﬂu- cat is stable. Communication with the client is
ids may be all that is necessary to lower the of utmost importance. A broad knowledge of
body temperature to a safer level. Antipyretics the possible causative diseases and the ability
(e.g., ketoprofen, ﬂunixin meglumine, dipy- to interpret speciﬁc diagnostic test results in
rone) are not typically advocated because the the context of FUO in cats is essential to cor-
fever can be beneﬁcial, and many argue that rectly diagnose the source of an FUO.
TO LEARN MORE
antipyretic therapy can have a negative impact
For more information on Acknowledgments
on immune responses by causing hypothermia
special tests that can be The author thanks Robin W. Allison, DVM,
used in diagnosing the and impairing host immune defenses.3,4,31
PhD, DACVP, of the Department of Veterinary
cause of FUO in cats,
please visit the Web
For more information on the treatment of cats with Pathobiology at Oklahoma State University and Leo
Exclusives section of FUO, please refer to the treatment section in the “Ty” McSherry, DVM, DACVP, clinical pathologist
CompendiumVet.com. article starting on page 14. Many of the treatments at Antech Diagnostics in Irvine, California, for the
used in dogs can also be used in cats. cytology images.
1. Miller JB. Hyperthermia and fever of unknown origin. In: Etting- 5. Lappin MR. Fever of unknown origin I and II. Proc Western Vet
er SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. Conf 2003.
Vol 1. 6th ed. St. Louis: Elsevier Saunders; 2005:9-13. 6. Wolfe AM. Fever of undetermined origin in the cat. Proc Atl
2. Lunn KF. Fever of unknown origin: a systematic approach to Coast Vet Conf 2002.
diagnosis. Compend Contin Educ Pract Vet 2001;23(11):976-992. 7. Feldman BF. Fever of undetermined origin. Compend Contin
3. Johannes DM, Cohn LA. A clinical approach to patients with Educ Pract Vet 1980;2(12):970-977.
fever of unknown origin. Vet Med 2000;95(8):633-642. 8. Dunn JK, Gorman NT. Fever of unknown origin in dogs and
4. Couto CG. Fever of undetermined origin. In: Nelson RW, Couto cats. J Small Anim Pract 1987;28:167-181.
CG, eds. Small Animal Internal Medicine. 4th ed. St. Louis: Elsevier; 9. Roth AR, Basello GM. Approach to the adult patient with fever
2009:1274-1277. of unknown origin. Am Fam Phys 2003;68:2223-2228.
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The Diagnostic Approach to FUO in Cats CE
10. Mourad O, Palda V, Detsky AS. A comprehensive evidence- 20. Greene CE. Feline foamy (syncytium-forming) virus infection.
based approach to fever of unknown origin. Arch Intern Med In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 3rd ed.
2003;163:545-551. St. Louis: Elsevier Saunders; 2006:154-155.
11. Johnson DH, Cunha BA. Drug fever. Infect Dis Clin North Am 21. Calvert CA, Wall M. Cardiovascular infections. In: Greene CE,
1996;10:85-91. ed. Infectious Diseases of the Dog and Cat. 3rd ed. St. Louis: El-
12. Greene CE, Schultz RD. Immunoprophylaxis. In: Greene CE, ed. sevier Saunders; 2006:841-865.
Infectious Diseases of the Dog and Cat. 3rd ed. St. Louis: Elsevier 22. Malik R, Barrs VR, Church DB, et al. Vegetative endocarditis in
Saunders; 2006:1069-1119. six cats. J Feline Med Surg 1999;1(3):171-180.
13. Hartmann K. Feline leukemia virus infection. In: Greene CE, ed. 23. Greiner M, Wolf G, Hartmann K. Bacteraemia in 66 cats and an-
Infectious Diseases of the Dog and Cat. 3rd ed. St. Louis: Elsevier timicrobial susceptibility of the isolates (1995–2004). J Feline Med
Saunders; 2006:105-131. Surg 2007;9(5):404-410.
14. Sellon RK, Hartmann K. Feline immunodeﬁciency virus infec- 24. Dawson S, Bennett D, Carter SD, et al. Acute arthritis of cats associ-
tion. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 3rd ated with feline calicivirus infection. Res Vet Sci 1994;56(2):133-143.
ed. St. Louis: Elsevier Saunders; 2006:131-143. 25. Liehmann L, Degasperi B, Spergser J, et al. Mycoplasma felis
15. Dow SW, Jones RL, Henik RA, et al. Clinical features of salmonello- arthritis in two cats. J Small Anim Pract 2006;47(8):476-479.
sis in cats: six cases (1981–1986). JAVMA 1989;194(10):1464-1466. 26. Carro T, Pedersen NC, Beaman BL, et al. Subcutaneous ab-
16. Rossi M, Hanninen ML, Revez J, et al. Occurrence and species scesses and arthritis caused by a probable bacterial L-form in cats.
level diagnostics of Campylobacter spp., enteric Helicobacter spp. JAVMA 1989;194(11):1583-1588.
and Anaerobiospirillum spp. in healthy and diarrheic dogs and cats. 27. Pedersen NC, Pool RR, O’Brien T. Feline chronic progressive
Vet Microbiol 2008;129(3-4):304-314. polyarthritis. Am J Vet Res 1980;41(4):522-535.
17. Fox JG. Enteric bacterial infections. In: Greene CE, ed. Infec- 28. Bennett D. Immune-mediated and infective arthritis. In: Ettinger
tious Diseases of the Dog and Cat. 3rd ed. St. Louis: Elsevier Saun- SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. Vol
ders; 2006:339-369. 2. 6th ed. St. Louis: Elsevier Saunders; 2005:1958-1965.
18. Wess G, Unterer S, Haller M, et al. Recurrent fever as the only 29. Battersby IA, Murphy KF, Tasker S, et al. Retrospective study of
or predominant clinical sign in four dogs and one cat with con- fever in dogs: laboratory testing, diagnoses and inﬂuence prior to
genital portosystemic vascular anomalies. Schweiz Arch Tierheilkd treatment. J Small Anim Pract 2006;47:370-376.
2003;145(8):363-368. 30. Hanna FY. Disease modifying treatment for feline rheumatoid
19. Dubey JP, Lappin MR. Toxoplasmosis and neosporosis. In: arthritis. Vet Comp Orthop Traumatol 2005;18(2):94-99.
Greene CE, ed. Infectious Diseases of the Dog and Cat. 3rd ed. St. 31. Klein NC, Cunha BA. Treatment of fever. Infect Dis Clin North
Louis: Elsevier Saunders; 2006:754-775. Am 1996;10(1)211-216.
CREDITS CE TEST 2
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Those who wish to apply this credit to fulﬁll state relicensure requirements should consult their respective state authorities
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1. An example of a true fever would be an 5. The underlying predisposing causes of 9. Which statement regarding fever in cats
elevated body temperature bacteremia in cats include is true?
a. secondary to heatstroke. a. pneumonia. a. Cats with true fevers typically have body
b. associated with a drug reaction. b. pyelonephritis. temperatures greater than 106°F.
c. secondary to a prolonged seizure. c. gastrointestinal tract disease. b. Cats are not affected by stress hyper-
d. secondary to malignant d. all of the above thermia; therefore, a thorough diagnos-
hyperthermia. tic evaluation should immediately be
6. The most common cause of FUO in cats is conducted on every febrile cat.
2. Stage 1 diagnostic testing for cats with a. neoplasia. c. A subtle subcutaneous swelling on
FUO should include b. infectious disease. the limb of a febrile cat can be ignored
a. urinalysis. c. immune-mediated disease. because it is an unlikely cause of fever.
b. ultrasonography. d. none of the above d. About 50% of FUOs in cats remain undi-
c. arthrocentesis. agnosed despite thorough diagnostic
d. biopsy. 7. __________ has been reported to cause evaluation.
FUO in cats.
3. __________ examination should be con- a. A portosystemic shunt c. Lymphadenitis 10. Which statement regarding testing in
ducted repeatedly in cats with an FUO. b. Polyarthritis d. all of the above cats with FUO is true?
a. Physical c. Neurologic a. FeLV and FIV tests do not need to be
b. Fundic d. all of the above 8. Thoracic radiography should be conducted conducted in cats previously tested for
a. in all cats with FUO. these diseases.
4. Which is not known to be associated b. if ultrasonography results indicate b. A serum bile acids assay is never indi-
with polyarthritis in cats? respiratory disease. cated in a cat with FUO.
a. feline infectious peritonitis c. if the minimum database does not c. A blood smear should be evaluated along
b. mycoplasma reveal the cause of the FUO. with the CBC for every cat with an FUO.
c. calicivirus d. only in cats with clinical signs of respi- d. Bone marrow aspiration is indicated
d. L-form bacterial infection ratory disease. only when the CBC is abnormal.
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 31
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32 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
35. CE Article 3 3 CE
for Canine Immune-Mediated
❯❯ Suliman Al-Ghazlat, BVSc, Abstract: The mortality for dogs with severe immune-mediated hemolytic anemia (IMHA) is unaccept-
DACVIMa ably high, and better immunosuppressive regimens are needed to increase survival. Understanding
NYC Veterinary Specialists the basic immunology of the disease and the mechanisms of action of the available immunosuppres-
Forest Hills, New York
sive therapies will help clinicians choose an appropriate immunosuppressive protocol. Prospective,
randomized clinical studies must be conducted to evaluate the efﬁcacy and safety of different com-
bined immunosuppressive modalities to treat canine IMHA and improve patients’ outcomes.
he pathogenesis of canine immune- Treatment Options
mediated hemolytic anemia (IMHA) Current immunosuppressive therapies for
At a Glance involves the production of immuno- IMHA act by a variety of mechanisms,
Treatment Options globulin (Ig) that recognizes either a self but ultimately they all suppress antibody
Page 33 (autoimmune) antigen or a foreign (immune- production by lymphocytes and/or inhibit
mediated) antigen associated with red blood the clearance of opsonized RBCs by mac-
cells (RBCs). This results in sensitization or rophages or lysis by the complement sys-
opsonization of the RBCs and their subse- tem.5,12–14 Because the half-life of IgG (the
Page 35 quent destruction by the complement system, antibody class involved in most cases of
the mononuclear phagocyte system, or both.1–3 canine IMHA) in dogs is approximately 1
Management of Relapse The interaction of RBC surface-bound Ig with week, therapies directed only at suppres-
protein crystallizable fragment receptors (FcRs) sion of antibody production are unlikely
on different cells in the immune system leads to affect the outcome in the acute phase
to a wide range of immune responses, includ- of the disease.13,14
ing antibody-dependent cellular cytotoxicity, Over the past 25 years, great advances
phagocytosis, complement activation, mast cell have been made in the field of immu-
degranulation, lymphocyte proliferation, anti- nology, especially in the development
body secretion, and enhancement of antigen of new immunosuppressive agents (e.g.,
presentation. These responses also promote cyclosporine, leflunomide, mycopheno-
phagocytosis and clearance of opsonized late mofetil) that are more potent, more
RBCs by the mononuclear phagocyte system selective, and less toxic than glucocorti-
cells and lead to intravascular hemolysis by coids.5,14,15 The wide array of new drugs
full activation of complement.1,2,4,5 In severe offers the opportunity to use combinations
cases, clinical signs of anemia progress that block different pathways of immune
rapidly, and animals may present in shock. activation while selecting agents with non-
Most dogs that succumb to IMHA do so overlapping toxicity proﬁles. Nonetheless,
within the ﬁrst 2 weeks after onset (acute IMHA mortality remains high, ranging
phase).3,6–11 A retrospective study of 60 dogs from 22% to 80%.2,3,6–11,16–18 Moreover, mul-
with IMHA showed a mortality of 52%, with tiple retrospective studies have shown that
a good long-term outcome in dogs that sur- the addition of cyclosporine, azathioprine,
vived the ﬁrst 2 weeks of the disease.11 or cyclophosphamide to glucocorticoids
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 33
CE Immunosuppressive Therapy for Canine IMHA
did not improve mortality.8,11 gastrointestinal (GI) signs at presentation. For
IMHA and its therapy can be divided into induction, the recommended dose is 2 mg/kg
three phases: induction of remission, mainte- bid for dogs weighing less than 6 kg and 1.1
nance of remission and prevention of relapse, mg/kg or 30 mg/m2 bid for those weighing
and management of relapse. The causes of more than 30 kg.2,17 Remission is signaled by a
death in dogs that die during the acute phase stable or rising packed cell volume (PCV) with
of IMHA are not well documented, but in addi- no clinical signs of decreased oxygen-carrying
tion to lack of response to immunosuppressive capacity over a period of 7 to 14 days. At this
agents, they include thromboembolic disease, time, the dose may be decreased by 25% to
sepsis, and other side effects of therapy, as 50% (depending on the severity of side effects)
well as reactions to antithrombotic therapy and and then by 25% every 2 weeks thereafter.2
blood transfusions.8,9,18 One way to improve Once a dose of 0.5 mg/kg sid is reached,
outcomes in the acute phase of IMHA is to the patient can be switched to alternate-day
focus the induction of immunosuppression prednisone therapy. As the side effects of pred-
on manipulating FcR/Ig interactions, reducing nisone at this point are typically mild, decreas-
phagocytosis, and inhibiting complement. The ing the dose by 25% every 4 to 6 weeks rather
causes of death during the maintenance phase than every 2 weeks is generally advisable.
of IMHA therapy are also unclear, but they may Prednisone administration can be completely
be related to disease recurrences or side effects discontinued if there are no signs of relapse
of immunosuppression. To improve outcomes while the patient is receiving 0.25 mg/kg every
and minimize relapses in this phase, mainte- other day for 4 to 6 weeks (TABLE 1). A com-
nance immunosuppressive therapy should be plete blood count (CBC) should be obtained
potent, speciﬁc, and associated with few or no before any decrease in the dose of immuno-
side effects. suppressive agents. A less aggressive tapering
protocol may be advised when glucocorti-
Glucocorticoids coids are used as the sole immunosuppressive
Glucocorticoids remain the mainstay of immu- agent. Although most dogs can be completely
nosuppressive therapy for canine IMHA. Their weaned from glucocorticoids, a few patients
activity is largely derived from their ability may require lifelong, low-dose therapy to
QuickNotes to repress the transcription of many genes maintain remission.2,11 This prednisone proto-
responsible for encoding proinﬂammatory col is based solely on my clinical experience,
The mortality for cytokines and adhesion molecules that inﬂu- and there are no published studies establish-
dogs with severe ence immune cell trafﬁcking and cellular inter- ing its superiority.
IMHA is high, with actions. The molecular basis of glucocorticoid Adverse effects of glucocorticoids include
most deaths occur- action lies in the capacity to diffuse through iatrogenic hyperadrenocorticism, GI ulcer-
ring within the ﬁrst the cell membrane and bind to cytosolic ste- ation and perforation, recurrent infections,
2 weeks of clinical roid receptors, which subsequently undergo sepsis, and thromboembolic disease.21–23
disease. nuclear translocation and modulate tran- Glucocorticoids may also predispose patients
scriptional activation.5,12,19,20 The main effect to pancreatitis, although this has not been
of glucocorticoids in the treatment of IMHA proven.24 Based on clinical experience, large-
is to suppress complement and phagocytosis and giant-breed dogs are especially sensitive
of opsonized RBCs by interfering with the to adverse effects of glucocorticoids. In con-
expression and function of macrophage FcRs, trast, most dogs weighing less than 6 kg gen-
which is an immediate effect.5,20 erally experience only mild adverse effects.
Prednisone (2 mg/kg bid) is commonly Dexamethasone is considered by some clini-
used to induce remission in IMHA, and a vari- cians to be superior to prednisone in induc-
ety of dosages and protocols have been advo- ing IMHA remission, but there are no studies
cated.1–3,5–11,16–18 There have been no studies to to support this opinion, and (anecdotally) GI
evaluate the effect of different prednisone dos- ulceration and pancreatitis are more common
ages on short- or long-term outcomes. Factors with dexamethasone than with prednisone.13,14
that may inﬂuence dosing include patient In addition, due to its longer duration of effect
size, body condition, breed, disease sever- in suppressing the hypothalamic–pituitary–
ity, concurrent illnesses, and the presence of adrenal axis, dexamethasone is not appropri-
34 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
Immunosuppressive Therapy for Canine IMHA CE
TABLE 1 Suggested Immunosuppressive Protocol
This protocol is for a 25-kg dog with a body condition score of 5/9, using prednisone for induction of remission and azathioprine to help with
maintenance, and is based on clinical experience.
Day 1 Prednisone at 30 mg PO bid or, if the dog cannot tolerate oral medication,
dexamethasone at 9 mg IV sid
Day 5 No GI disturbance for at least 48 hr Maintain prednisone at 30 mg bid and add azathioprine at 50 mg PO sid
Day 7 PCV is stable or rising for the previous 48 hr and there Discharge the patient from the hospital and continue the same medications
are no signs of GI disturbance
Day 14 PCV is rising but subnormal, with no signs of Obtain a CBC and chemistry proﬁle
myelotoxicity/hepatotoxicity or serious glucocorticoid side Maintain prednisone at 30 mg bid
effects Decrease azathioprine to 50 mg q48h
Day 21 PCV is normal, with no signs of myelotoxicity or Obtain a CBC
serious glucocorticoid side effects Decrease prednisone to 20 mg bid
Maintain azathioprine at 50 mg q48h
Day 28 (week 4) PCV is normal, with no signs of Obtain a CBC
myelotoxicity or serious glucocorticoid side effects Maintain prednisone at 20 mg bid
Maintain azathioprine at 50 mg q48h
Week 5 No signs of relapse, myelotoxicity, or hepatotoxicity Obtain a CBC and chemistry proﬁle
Decrease prednisone to 15 mg bid
Maintain azathioprine at 50 mg q48h
Week 7 No signs of relapse or myelotoxicity Obtain a CBC
Decrease prednisone to 10 mg bid
Maintain azathioprine at 50 mg q48h
Week 9 No signs of relapse or myelotoxicity Obtain a CBC
Decrease prednisone to 15 mg sid
Maintain azathioprine at 50 mg q48h
Week 11 No signs of relapse or myelotoxicity/hepatotoxicity Obtain a CBC and chemistry proﬁle.
Decrease prednisone to 10 mg sid
Maintain azathioprine at 50 mg q48h
Week 13 No signs of relapse or myelotoxicity Obtain a CBC
Decrease prednisone to 5 mg q48h
Maintain azathioprine at 50 mg q48h
Week 17 No signs of relapse or myelotoxicity/hepatotoxicity Obtain a CBC and chemistry proﬁle
Maintain azathioprine at 50 mg q48h
Week 23 No signs of relapse or myelotoxicity/hepatotoxicity Obtain a CBC and chemistry proﬁle
Decrease azathioprine dose to 50 mg q 3 days
Week 27 No signs of relapse Obtain a CBC
Week 30 No signs of relapse Recommend a CBC q 2 mo for the ﬁrst year and biannually to triennially thereafter
CBC = complete blood count; PCV = packed cell volume.
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 35
CE Immunosuppressive Therapy for Canine IMHA
ate for alternate-day therapy. Because the main Danazol
effect of glucocorticoids in treating IMHA is Danazol is an androgen derivative used in the
to suppress complement and FcR-mediated early 1990s as an adjunctive treatment for canine
clearance of opsonized RBCs, glucocorticoids immune-mediated thrombocytopenia.33,34 Similar
are the drugs of choice in the induction phase to glucocorticoids, danazol (10 to 15 mg/kg sid)
of treatment. However, as glucocorticoids can may inhibit binding of the Fc portion of immu-
have severe side effects when used chronically noglobulin to FcRs and hence prevent phago-
at high doses, they are not ideal for maintain- cytosis of opsonized RBCs.33,35 However, in one
ing remission and preventing relapse. preliminary report of a small, prospective study
in dogs with IMHA, adding danazol did not
Human Intravenous Immunoglobulin show any signiﬁcant beneﬁcial effects compared
Human IV immunoglobulin (hIVIG) is a ster- with prednisone alone.35 Danazol is an anabolic
ile, puriﬁed IgG preparation manufactured steroid and can cause dramatic weight gain in a
from pooled human plasma that typically short time, especially when used in combination
contains more than 95% unmodiﬁed IgG, with prednisone. Furthermore, danazol is expen-
which has intact Fc-dependent effector func- sive and may be hepatotoxic.36 Due to these side
tions, and only trace amounts of IgA and IgM. effects of chronic use, danazol is not recom-
Several mechanisms of action have been pro- mended to maintain remission.
posed, including antiidiotypic activity, inhibi-
tion of autoantibody production, acceleration Splenectomy
of autoantibody breakdown and removal, and Splenectomy may be considered for patients
suppression of complement activation.25–32 Most with IMHA that fail to respond to, or have severe
importantly, hIVIG may reduce Fc-mediated adverse effects from, immunosuppressive ther-
phagocytosis of IgG-coated RBCs.25,26 One apy or that require long-term, high-dose therapy
study showed that hIVIG binds to canine lym- to remain in remission. The spleen is a major
phocytes and monocytes and inhibits RBC site of autoantibody production and of seques-
phagocytosis.26 tration and destruction of IgG-sensitized RBCs.
hIVIG has been used successfully in mul- A thorough search for an underlying infection
tiple studies to treat a small number of dogs is mandatory before proceeding with splenec-
QuickNotes with IMHA.31,32 A total infusion of 0.5 to 2 g/ tomy. Preliminary results of a small, prospective,
kg administered in a divided dose on 2 con- unpublished study showed that splenectomy
Glucocorticoids secutive days over a period of 6 to 12 hours as an adjunctive therapy is superior to medical
are the mainstay of has been beneﬁcial in some refractory cases therapy alone in reducing mortality and short-
immunosuppressive of canine nonregenerative IMHA.31 No signiﬁ- ening the interval to normal PCVs in dogs with
therapy for canine cant side effects were reported in these lim- severe IMHA.37 In fact, splenectomy may be
IMHA, but they can ited samples.31,32 effective for both remission induction and main-
cause serious side Due to its rapid onset of action and poten- tenance therapy for severe IMHA. It may also
effects. tial to block the phagocytosis of sensitized be helpful in dogs with multiple acute relapses
RBCs, hIVIG may be useful in the induction or in those that only partially respond to medi-
of remission in dogs with severe IMHA. In the cal immunosuppression. However, as the site
few reported cases, the response was often of clearance of IgM-sensitized RBCs appears
rapid but transient, suggesting that hIVIG is to be the hepatic Kupffer cells, splenectomy is
not ideal for maintaining remission.31,32 Indeed, unlikely to be beneﬁcial in dogs with positive
it is potentially immunogenic in dogs, and Coombs’ test results or IgM autoantibodies.38
repeated infusions could induce acute anaphy- No large-scale studies have evaluated the
laxis. There are no studies on the efﬁcacy and short- and long-term safety of splenectomy in
the safety of repeated hIVIG infusions in dogs. dogs. Due to the cost of surgery and risk of
Although hIVIG is expensive ($600 for a 5-g complications, splenectomy is rarely recom-
bottle), it may be practical and economical to mended as a ﬁrst-line therapy for severe IMHA.
use for induction of remission if it signiﬁcantly On the other hand, given the encouraging pre-
decreases hospitalization time and transfusion liminary data, further studies to evaluate the
requirements. Repeated maintenance infusions safety and efﬁcacy of splenectomy in the treat-
are currently not recommended. ment of canine IMHA are warranted.
36 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
Immunosuppressive Therapy for Canine IMHA CE
Plasmapheresis on reducing levels of circulating antierythro-
Plasmapheresis is a process whereby the com- cyte antibodies. As such, it is probably inef-
ponents in plasma believed to cause or exac- fective for remission induction during the
erbate disease are removed. The remaining acute phase of IMHA.
blood components are then combined with One retrospective study showed no ben-
replacement plasma or an inert substitute and eﬁcial effect of adding cyclophosphamide
returned to the patient.39,40 The clinical effec- to prednisone in 60 dogs with IMHA,11 and
tiveness of plasmapheresis in the treatment of another study showed higher mortality in dogs
autoimmune disease may be due to the partial so treated compared with dogs that received
removal of autoantibodies, immune complexes, prednisone alone.8 Interpretation of these
complement components, proinﬂammatory studies is complicated by their retrospective
agents, and soluble adhesion molecules.39 nature, and it is likely that cyclophosphamide
Plasmapheresis is most useful for rapidly was used only in the more severe cases.
reducing plasma concentrations of autoan- However, a small, randomized, prospective
tibodies or immune complexes while other trial found no beneﬁcial effects from adding
immunosuppressive measures are applied cyclophosphamide to prednisone in the man-
to prolong the effect.39 One study reported agement of acute IMHA and even suggested
encouraging results for plasmapheresis in dogs that cyclophosphamide may adversely affect
with systemic immune-mediated diseases.40 outcome.10 Indeed, several in vitro and in vivo
The study suggested that any dog with an experimental studies suggest that cyclophos-
acute immune-mediated disease refractory to phamide may paradoxically augment immune
conventional immunosuppressive therapy can responses through a toxic effect on T regula-
be considered for plasmapheresis.40 Although tory cells.43 Cyclophosphamide also has seri-
there are no reported clinical trials of plas- ous adverse effects, including gastroenteritis,
mapheresis for IMHA, it may be helpful in myelosuppression, sterile hemorrhagic cystitis,
acute, refractory cases or cases complicated and secondary neoplasia.5,44,45 Based on this
by concurrent systemic infection.41 However, evidence, cyclophosphamide is not recom-
availability of plasmapheresis is limited in vet- mended for induction of remission in dogs
erinary medicine, and experience with its use with IMHA, and the risk–beneﬁt proﬁle should
for treating animals with immune-mediated be considered carefully before it is used for QuickNotes
diseases is minimal. maintenance therapy.
Due to its rapid
Cyclophosphamide Azathioprine onset of action,
Cyclophosphamide is a cytotoxic, myelosup- Azathioprine is a cy totoxic antimetabo- human intravenous
pressive alkylating agent. It cross-links DNA lite that is conver ted to 6 -mercaptopu- immunoglobulin
helixes to prevent their separation, thus pre- rine in the liver. It is a purine analogue may be a good
venting the formation of a DNA template.5,42 that functions as a competitive purine choice in the initial
Cyclophosphamide is toxic to both resting antagonist, thereby inhibiting cellular pro- management of
and dividing cells, particularly proliferating liferation.5,12,46 Azathioprine is less toxic to
immune cells (lymphocytes).5 It suppresses resting cells than cyclophos phamide and
both cell-mediated and humoral immunity, therefore has fewer side effects. It primarily
and it may suppress mononuclear phago- suppresses lymphocyte activation and pro-
cytic function.5,12 Historically and anecdot- liferation, reducing antibody production. In
ally, cyclophosphamide has been effective in vivo experimental studies have shown that
inducing and maintaining remission in dogs azathioprine may help to establish antigen-
with fulminant IMHA. Several authors have specific tolerance and decrease the risk of
recommended using cyclophosphamide in relapse.47 Azathioprine also suppresses mac-
cases in which intravascular hemolysis or rophage function, which reduces inflamma-
autoagglutination is present, suggesting that it tory cytokine production and phagocytic
is especially effective in IgM-mediated hemol- efficiency.4,5 The onset of action of azathio-
ysis.5 However, cyclophosphamide principally prine is slow in people but appears to be
targets lymphocyte proliferation and, there- faster in dogs, with immunosuppressive
fore, is unlikely to have an immediate effect effects evident in 2 to 4 weeks.
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 37
CE Immunosuppressive Therapy for Canine IMHA
Several studies have suggested a beneﬁ- properties through its blockage of transcrip-
cial effect of azathioprine in the treatment of tion of cytokine genes in activated T cells.
canine IMHA.6,11,17 However, as these studies CsA inhibits the phosphatase activity of cal-
are retrospective and lack data on azathio- cineurin, thereby preventing activation of the
prine timing and dosing and because mul- nuclear factor of activated T cells (NFAT).5,12,52
tiple concurrent immunosuppressive and NFAT activation and nuclear translocation are
antithrombotic agents were used, it is difﬁcult required for the transcription of many cytok-
to attribute the improved survival directly to ines, particularly interleukin-2 (IL-2), which
use of azathioprine. A large, retrospective is necessary for the proliferation and matura-
study showed that in dogs treated for IMHA tion of T cells.5,52,53 CsA also enhances expres-
with the combination of prednisone, azathio- sion of transforming growth factor-β (TGF-β),
prine, and ultralow-dose aspirin (0.5 mg/kg which is a potent inhibitor of IL-2–stimulated
sid), the survival rates at discharge, 1 month, T cell proliferation and generation of antigen-
and 1 year were 88%, 82%, and 69%, respec- speciﬁc cytotoxic lymphocytes.5,52 Studies indi-
tively, which compared favorably with rates in cate that CsA blocks the activation of C-Jun N
previously reported studies (57%, 58%, 34%).17 terminal kinases and p38 signaling pathways
Due to azathioprine’s slow onset of action, it triggered by antigen recognition, making CsA
is unlikely to play any role in improving short- a highly speciﬁc inhibitor of T cell activation.12
term survival. The recommended canine load- In addition, by suppressing the production of
ing dose is 2 mg/kg sid for 5 to 7 days, followed interferon γ, CsA may inhibit the phagocytic
by 2 mg/kg every other day for maintenance.17 capabilities of macrophages.5,53
I generally continue azathioprine maintenance The efﬁcacy of CsA has been demonstrated
until the patient has been weaned off predni- in cats and dogs undergoing renal transplan-
sone for 4 weeks. There is no well-established tation and in dogs with immune-mediated
dose-tapering protocol for azathioprine, but I disorders.54 One retrospective study showed
taper the dose gradually over 2 to 3 months by improved outcome in dogs with IMHA that
extending the period of time between doses received CsA and glucocorticoids compared
by 1 day every 4 weeks (TABLE 1). with glucocorticoids alone, but the difference
The most common adverse effects of azathi- did not reach statistical signiﬁcance.8 This
QuickNotes oprine therapy are GI disturbances and myelo- ﬁnding suggests that CsA may be superior to
suppression, particularly in large dogs.46,48,49 glucocorticoids alone, as CsA was likely added
Cyclophosphamide Acute pancreatitis and cholestatic hepatopa- only in the more severe cases. Preliminary
is not recom- thy have been anecdotally reported in dogs results from a prospective study showed no
mended for induc- receiving azathioprine.48,50,51 The prognosis beneﬁcial effect from combining CsA with
tion of remission in for azathioprine-induced bone marrow toxic- prednisone on the survival of dogs with IMHA
dogs with IMHA. ity is good if the drug is discontinued before in the ﬁrst 28 days after onset.55 However, four
severe myeloﬁbrosis occurs.49 Therefore, a of the 19 dogs in the prednisone-only group
CBC should be obtained every week for the experienced relapses compared with none in
ﬁrst month of azathioprine therapy and every the combination group. This study has not
4 weeks for the duration of therapy, and the yet been published, and the number of sub-
drug should be discontinued immediately if jects was small. In addition, a relatively small
the neutrophil count declines signiﬁcantly. dose of CsA was used (4 mg/kg sid), and there
Due to its slow onset of immunosuppressive was no mention of monitoring drug levels.
action, azathioprine is not a drug of choice for Generally, a dosing regimen of 5 to 10 mg/kg
induction of remission. Conversely, due to its sid is recommended for dogs, and plasma con-
selective immunosuppressive effects, few side centrations should be periodically monitored
effects, availability, and relatively low cost, it is to achieve an effective but safe trough level
a good choice for maintenance therapy. (400 to 500 ng/mL); an optimal level has not
Cyclosporine A The most common side effects of CsA in
Cyclosporine A (CsA) is a cyclic polypep- dogs include GI irritation, gingival hyper-
tide metabolite of the fungus Tolypocladium plasia, antibiotic-responsive dermatitis, and
inﬂatum. It has potent immunosuppressive papillomatosis.5,54,56 Malignancies, including
38 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
Immunosuppressive Therapy for Canine IMHA CE
lymphoma and squamous cell carcinoma, dogs are especially sensitive to the adverse GI
have been noted as well.57,58 In addition, effects (e.g., diarrhea, vomiting) of this drug.61
anaphylaxis has been reported in people There are no reports on the use of MMF to
and dogs receiving IV CsA.59 CsA-associated manage canine IMHA, but based on its mech-
nephrotoxicosis is a well known complica- anism of immunosuppressive action, it should
tion in people but appears to be rare in dogs be investigated for maintenance of remission.
and cats whose serum CsA levels are main-
tained within the therapeutic range (400 to Leflunomide
500 ng/mL).54 CsA is expensive and requires Leﬂunomide is a synthetic isoxazole derivative
blood level monitoring, which usually makes that is metabolized in the gut and liver.60 The
it cost-prohibitive for large dogs. However, active metabolite of leﬂunomide, A77 1726,
due to its potent and speciﬁc suppressive reversibly inhibits dihydro-orotate dehydro-
effects on lymphocyte proliferation and genase, the rate-limiting enzyme in the de
autoantibody production and tolerable side novo synthesis of pyrimidines.12,52,60,65–67 Again,
effects even when used chronically, it may be lymphocytes need both the salvage and the
a good choice for maintenance. In addition, de novo pathways of pyrimidine synthesis to
due to its suppression of phagocytosis, it may meet the high demand for pyrimidines dur-
be beneﬁcial during the induction phase of ing lymphocyte activation and proliferation.
therapy. 5,53 Leﬂunomide speciﬁcally suppresses activated
T and B cells while other cells maintain their
Mycophenolate Mofetil basal cell division. Experimental transplanta-
Mycophenolate mofetil (MMF) is a fermenta- tion studies showed that A77 1726 prevents
tion product of several Penicillium spp that antibody production.60 Leﬂunomide also inhib-
is metabolized completely in the plasma and its the production of proinﬂammatory cytok-
liver into its active metabolite, mycophenolic ines (e.g., IL-1, tumor necrosis factor α) and
acid (MPA).60–62 MPA is an effective, reversible augments the production of the antiinﬂamma-
inhibitor of inosine monophosphate dehy- tory cytokine TGF-β, culminating in signiﬁcant
drogenase (IMPDH), which is a key enzyme antiinﬂammatory effects.43,52,61,65
in de novo purine biosynthesis.12,52,60–62 Most One study reported promising results of the
other cell lines can maintain their function use of leﬂunomide for treatment of immune- QuickNotes
through the salvage pathway of purine bio- mediated and inﬂammatory diseases in dogs
synthesis alone, but proliferating lymphocytes refractory to conventional therapy.65 In this
depend on both the salvage pathway and the study, 26 dogs with different immune-medi- sive regimen is only
de novo pathway. Due to the high speciﬁc- ated diseases were treated with leﬂunomide, one part of a com-
ity of MPA for IMPDH, MPA is a very selec- including six dogs with IMHA. Five of these six prehensive thera-
tive lymphocyte inhibitor.60,61,63 Blockade of dogs responded well to leﬂunomide therapy, peutic approach to
IMPDH by MPA was shown to deplete the and the one dog that died had severe myeloﬁ- improve the out-
guanosine pool in lymphocytes and to inhibit brosis that was probably related to the primary come of dogs with
T- and B-cell proliferation, differentiation of disease. The initial dose of leﬂunomide was
alloreactive cytotoxic T cells, and antibody 4 mg/kg/day, but the dose was adjusted to
responses.60–62 Other mechanisms that may obtain a target trough A77 1726 plasma level
contribute to the immunosuppressive effects of 20 μg/mL.67 Most of the dogs had mild to
of MPA include induction of apoptosis of acti- moderate disease or partial response to con-
vated T cells and impairment of the matura- ventional therapy, affording sufﬁcient time for
tion of dendritic cells.64 leﬂunomide to exert its immunosuppressive
MMF has been shown to be safe and effec- effects.
tive in prolonging the survival of canine Leﬂunomide is not commonly used in vet-
experimental renal allografts and, anecdotally, erinary medicine, so adverse effects are not
has been used successfully in several cases of well documented. Adverse effects reported
canine immune-mediated disease.61,62 The rec- in a small number of dogs were rare and
ommended starting MMF dose for dogs is 20 mild, including decreased appetite, lethargy,
to 40 mg/kg/day PO divided into two or three mild anemia, and self-limiting GI signs.65
doses.62 Experimental studies showed that However, most of the dogs in the study were
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 39
CE Immunosuppressive Therapy for Canine IMHA
concurrently receiving other immunosup- can be managed by increasing the dose to the
pressive agents that may have contributed to previous level. This dog can be managed as
these effects. Based on this single study of an outpatient if it is asymptomatic for anemia,
dogs with IMHA, it seems that leﬂunomide but its CBC should be reevaluated in 1 week
may be an effective immunosuppressive drug to assess the efﬁcacy of therapy. Importantly,
with minimal side effects and should be inves- a drop in PCV for a dog with IMHA does not
tigated for maintenance of remission of canine always signal a relapse. Other causes of a
IMHA. decreased PCV in dogs receiving immunosup-
pressive therapy for IMHA include sepsis and
Mizoribine GI hemorrhage. Failure to identify patients
Mizoribine is an imidazole nucleoside, and its with these complications can be detrimental
active metabolite (mizoribine monophosphate) and potentially fatal.
is a potent inhibitor of IMPDH.52,68 Therefore,
like MMF, it blocks purine biosynthesis in B Conclusion
and T cells and inhibits their proliferation. Canine patients with severe IMHA have a
The antiproliferative effect of mizoribine is guarded prognosis. Despite the introduction of
linked to a decrease in guanine ribonucle- several new immunosuppressive agents, mor-
otide pools. Mizoribine has been approved in tality remains high.2,3,5–7,12–16 Glucocorticoids
Japan for renal transplant recipients and is cur- are the mainstay of IMHA therapy for induc-
rently undergoing clinical testing in Europe as tion of remission, but the addition of more
a substitute for azathioprine in human renal potent immunosuppressive agents to pred-
transplant recipients. It appears to be safe and nisone therapy may be warranted in severe
(unlike azathioprine) to have minimal myelo- cases and in patients with major adverse
toxicity or hepatotoxicity. The availability of glucocorticoid effects. Because azathioprine,
this drug is very limited, and little is known CsA, leﬂunomide, and MMF are unlikely to
about its safety and efﬁcacy in veterinary med- have immediate beneﬁcial effects in dogs
icine, but theoretically, it could be employed with IMHA but may have immediate adverse
for the maintenance of IMHA remission. reactions, I generally wait to add one of these
agents to glucocorticoid therapy until the PCV
Management of Relapse is stable and the dog exhibits no GI distur-
The relapse rate for canine IMHA is not well bances. At my institution, the most common
documented, but retrospective studies suggest immunosuppressive agents used in combina-
that it is relatively high (13% to 20%).8,9,11,16,17 tion with prednisone for severe IMHA are CsA
Clinicians must monitor patients for relapse and azathioprine. CsA is faster acting and has
(Table 1), make a prompt diagnosis, assess the fewer side effects than azathioprine, but it can
severity and the acuteness of the relapse, and be cost prohibitive in large dogs. Preliminary
institute an appropriate immunosuppressive results seem promising for leﬂunomide and
protocol. The choice of regimen depends on discouraging for cyclophosphamide, but there
the severity of the relapse. A patient with an are few published prospective, randomized
acute relapse (e.g., drop in PCV from normal trials evaluating the use of various immuno-
to 25% or lower) should be hospitalized for suppressive agents used in combination with
supportive care and aggressively treated to prednisone versus prednisone alone.
reinduce remission. Immunosuppressive doses Immunosuppressive therapy is only one part
of glucocorticoids are the mainstay of therapy of a comprehensive approach to improving the
for relapse; adjunctive induction therapies for outcome of IMHA. Other therapies being stud-
severe, refractory cases include hIVIG, sple- ied include antithrombotic agents; one large,
nectomy, and plasmapheresis. retrospective study showed improved survival
On the other hand, a patient with a mild in dogs with IMHA that were treated with
relapse while being weaned off immunosup- ultralow-dose aspirin to prevent thromboem-
pressive therapy can be managed less aggres- bolic complications.17 The timing, volume, and
sively. For example, a dog in which the PCV type of oxygen-carrying support provided by
drops from 40% to 35% after the prednisone blood products or blood substitutes is another
dose is decreased from 1.5 to 1 mg/kg/day area that requires further investigation.
40 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
Immunosuppressive Therapy for Canine IMHA CE
1. Baker RN. Anemia associated with immune responses. In: Feld- 29. Byrne KP, Giger U. Use of human immunoglobulin for the treatment
man BF, Zinkl JG, Jain NC, et al, eds. Schalm’s Veterinary Hematol- of severe erythema multiforme in a cat. JAVMA 2002;220:197-201.
ogy. Baltimore: Lippincott Williams & Wilkins; 2000:169-175. 30. Nuttall TJ, Malham T. Successful intravenous human immuno-
2. McCullough S. Immune-mediated hemolytic anemia: under- globulin treatment of drug induced Stevens-Johnson syndrome in
standing the nemesis. Vet Clin Small Anim 2003;33:1295-1315. a dog. J Small Anim Pract 2004;45:357-361.
3. Klag AR, Giger U, Shofer FS. Idiopathic immune-mediated hemolytic 31. Scott-Moncrieff JCR, Reagan WJ, Glickman LT, et al. Treatment
anemia in dogs: 42 cases (1986–1990). JAVMA 1993;202:783-788. of nonregenerative anemia with human gamma globulin in dogs.
4. Heyman B. Regulation of antibody responses via antibodies, JAVMA 1995;206:1895-1900.
complement and Fc receptors. Ann Rev Immunol 2000;18:709-737. 32. Kellerman DL, Bruyette DS. Intravenous human immunoglobu-
5. Gregory CR. Immunosuppressive agents. In: Kirk RW, Bonagu- lin for the treatment of immune-mediated hemolytic anemia in 13
ra JD, eds. Kirk’s Current Veterinary Therapy XIII. Philadelphia: dogs. J Vet Intern Med 1997;11:327-332.
Saunders; 2000:509-513. 33. Jans HE, Armstrong PJ, Price GS. Therapy of immune-mediat-
6. Reimer ME, Troy GC, Warnick LD. Immune-mediated hemolytic ed thrombocytopenia: a retrospective study of 15 dogs. J Vet Intern
anemia: 70 cases (1988–1996). JAAHA 1999;35:384-391. Med 1990;4:4-7.
7. Duval D, Giger U. Vaccine-associated immune-mediated hemo- 34. Bloom JC, Meunier LD, Thiem PA, Sellers TS. Use of danazol
lytic anemia in the dog. J Vet Intern Med 1996;10:290-295. for treatment of corticosteroid-resistant immune-mediated throm-
8. Grundy SA, Barton C. Inﬂuence of drug treatment on survival of bocytopenia in a dog. JAVMA 1989;194(1):76-78.
dogs with immune-mediated hemolytic anemia: 88 cases (1989– 35. Miller E. Danazol therapy for the treatment of immune-mediated
1999). JAVMA 2001;218:543-546. hemolytic anemia in dogs (abstract). J Vet Intern Med 1997;11(2):130.
9. Carr AP, Panciera DL, Kidd L. Prognostic factors for mortal- 36. Welder AA, Robertson JW, Melchert RB. Toxic effects of an-
ity and thromboembolism in canine immune-mediated hemo- abolic-androgenic steroids in primary rat hepatic cell cultures. J
lytic anemia: a retrospective study of 72 dogs. J Vet Intern Med Pharmacol Toxicol Methods 1995;33:187-195.
2002;16:504-506. 37. Toll J, Aronsohn M. Prospective evaluation of medical therapy
10. Mason N, Duval D, Shofer FS, et al. Cyclophosphamide exerts with or without early splenectomy for treatment of severe immune-
no beneﬁcial effect over prednisone alone in the initial treatment of mediated hemolytic anemia in the dog (abstract). J Vet Intern Med
acute immune-mediated hemolytic anemia in dogs: a randomized 2003;17(3):383.
controlled clinical trial. J Vet Intern Med 2003;17:206-212. 38. Yan J, Vetvicka V, Xia Y, et al. Critical role of Kupffer cell CR3
11. Burgess K, Moore A, Rand W, Cotter SM. Treatment of immune- (CD11b/CD18) in the clearance of IgM-opsonized erythrocytes or
mediated hemolytic anemia in dogs with cyclophosphamide. J Vet soluble beta-glucan. Immunopharmacology 2000;46(1):39-54.
Intern Med 2000;14:456-462. 39. Bartges JW. Therapeutic plasmapheresis. Semin Vet Med Surg
12. Allison AC. Immunosuppressive drugs: the ﬁrst 50 years and a 1997;12(3):170-177.
glance forward. Immunopharmacology 2000;47(2-3):63-83. 40. Matus RE, Gordon BR, Leifer CE, et al. Plasmapheresis in
13. Couto CG. Use and misuse of immunosuppressants. Proc 20th ﬁve dogs with systemic immune-mediated disease. JAVMA
ACVIM Forum 2002;16:599. 1985;187(6):595-599.
14. Cohn L. Immune mediated blood dyscrasias: therapeutic opin- 41. Creager AJ, Brecher ME, Bandarenko N. Thrombotic throm-
ions. Proc 22nd Annu Forum Am Coll Vet Intern Med 2004:326-327. bocytopenic purpura that is refractory to therapeutic plasma ex-
15. Braun F, Lorf T, Ringe B. Update of current immunosuppressive drugs change in two patients with occult infection. Transfusion Pract
used in clinical organ transplantation. Transpl Int 1988;11(2):77-81. 1998;38:419-423.
16. Jackson ML, Kruth SA. Immune-mediated hemolytic anemia 42. Stanton M, Legendre A. Effects of cyclophosphamide in dogs
and thrombocytopenia in the dog: a retrospective study of 55 cas- and cats. JAVMA 1986;188:1319-1322.
es diagnosed from 1969 through 1983 at the Western College of 43. Su Y, Rolph M, Cooley M, Sewell W. Cyclophosphamide augments
Veterinary Medicine. Can Vet J 1985;26:245-250. inﬂammation by reducing immunosuppression in a mouse model of
17. Weinkle TK, Center SA, Randolph JF, et al. Evaluation of prognos- allergic airway disease. J Allergy Clin Immunol 2006;117(3):635-641.
tic factors, survival rates, and treatment protocols for immune-me- 44. Marin MP, Samson RJ, Jackson ER. Hemorrhagic cystitis in a
diated hemolytic anemia in dogs: 151 cases (1993–2002). JAVMA dog. Can Vet J 1996;37(4):240.
2005;226(11):1869-1880. 45. Ruther U, Nunnensiek C, Schmoll HJ. Secondary neoplasias
18. Scott-Moncrieff JC, Treadwell NG, McCullough SM, et al. He- following chemotherapy, radiotherapy and immunosuppression.
mostatic abnormalities in dogs with primary immune-mediated Contrib Oncol 2000;55:36-61.
hemolytic anemia. JAVMA 2001;37:220-227. 46. Beale KM. Azathioprine for treatment of immune-mediated dis-
19. Rhen T, Cidlowski JA. Anti-inﬂammatory action of glucocorticoids— ease of dogs and cats. JAAHA 1988;192:1316-1318.
new mechanisms for old drugs. N Engl J Med 2005;353(16):1711-1723. 47. Tiede I, Fritz G, Strand S, et al. CD28-dependent Rac1 activa-
20. Ruiz P, Gomez F, King M, et al. In vivo glucocorticoid modula- tion is the molecular target of azathioprine in primary human Cd4+
tion of guinea-pig splenic macrophage Fc-receptors. J Clin Invest T lymphocytes. J Clin Invest 2003;111(8):1133-1145.
1991;88:149-157. 48. Houston DM, Taylor JA. Acute pancreatitis and bone marrow sup-
21. Cosenza SF. Drug-induced gastroduodenal ulceration in dogs. pression in a dog given azathioprine. Can Vet J 1991;32(8):496-497.
Mod Vet Pract 1984;12:923-925. 49. Rinkardt NE, Kruth SA. Azathioprine-induced bone marrow tox-
22. Toombs JP, Collins LG, Graves GM, et al. Colonic perforation in icity in four dogs. Can Vet J 1996;37:612-613.
steroid-treated dogs. JAVMA 1986;188:145-150. 50. Perini GP, Bonadiman C, Fraccaroli GP, Vantini I. Azathioprine-
23. Casonato A, Pontara E, Boscar M, et al. Abnormalities of von related cholestatic jaundice in heart transplant patients. J Heart
Willebrand factor are also part of the prothrombotic state of Cush- Transplant 1990;9(5):577-578.
ing’s syndrome. Blood Coagul Fibrinolysis 1999;10:145-151. 51. King PD, Perry MC. Hepatotoxicity of chemotherapy. Oncolo-
24. Moriello KA, Bowen D, Meyer DJ. Acute pancreatitis in two dogs gist 2001;6:162-176.
given azathioprine and prednisone. JAVMA 1987;191(6):695-696. 52. Halloran PF. Molecular mechanisms of new immunosuppres-
25. Knezevic-Maramica I, Kruskall MS. Intravenous immune globu- sants. Clin Transplant 1996;10:118-123.
lins: an update for clinicians. Transfusion 2003;43:1460-1480. 53. Salom RN, Maquire JA, Hancock WW. Mechanism of a clinically
26. Reagan WJ, Scott-Moncrieff JC, Christian J, et al. Effects of hu- relevant protocol to induce tolerance of cardiac allografts. Perioper-
man intravenous immunoglobulin on canine monocytes and lym- ative donor spleen cells plus cyclosporine suppress IL-2 and inter-
phocytes. Am J Vet Res 1998;213(59):1568-1574. feron-gamma production. Transplantation 1993;56(6):1309-1314.
27. Rahilly LJ, Keating JH, O’Toole TE. The use of intravenous hu- 54. Robson D. Review of the pharmacokinetics, interactions and
man immunoglobulin in treatment of severe pemphigus foliaceus adverse reaction of cyclosporine in people, dogs and cats. Vet Rec
in a dog. J Vet Intern Med 2006;20:1483-1486. 2003;152:739-748.
28. Trotman TK, Phillips FH, King LG, et al. Treatment of severe 55. Husbands B, Polzin D, Armstrong PJ, et al. Prednisone and cy-
adverse cutaneous drug reactions with human intravenous immu- closporine vs prednisone alone for treatment of canine immune-mediat-
noglobulin in two dogs. JAAHA 2006;42:312-320. ed hemolytic anemia (IMHA) (abstract). J Vet Intern Med 2004;18:389.
CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 41
44. Quick Course
Factors to Consider When
Choosing Kitten Vaccines
At no time are cats at greater risk for of age.3 Studies have also shown that for adult cats, the AAFP strongly
disease than in the first few months of maternal antibody interference may recommends vaccinating kittens against
life.1 That’s why it’s important to vaccinate persist beyond 14 weeks of age.2–4 this disease. In an experimental study,
kittens early to induce immunity before To compensate for variations in susceptibility to FeLV decreased with
they are exposed to pathogens. maternal immunity, initial kitten age, but young kittens were most
“Maternal antibodies can block the vaccinations should begin at 6 to 8 vulnerable.6 Persistent viremia occurred
kitten’s ability to respond to a vaccine,”2 weeks of age and continue at 3- to 4- with 100% of cats infected with FeLV as
according to Alice Wolf, DVM, DACVIM, week intervals until the kitten is at least newborns, 85% of cats exposed between
DABVP, emeritus/adjunct professor 16 weeks of age.5 Practitioners are 2 weeks and 2 months of age, and 15%
at Texas A&M University College of encouraged to consult the 2006 of cats infected at 4 months to 1 year of
Veterinary Medicine and chief medical American Association of Feline age.6 Even though owners may claim a
consultant for the Veterinary Practitioners (AAFP) feline vaccination kitten is a strictly indoor pet, kittens can
Information Network. “Every kitten has guidelines for complete vaccine escape or owners may eventually allow
a different level of maternal antibodies— recommendations. them outdoors.
even kittens from the same litter—and
these antibodies can persist for different The Case for FeLV Vaccination Choosing the Right Vaccines
periods of time.” Some kittens have very Although vaccination for feline leukemia Some vaccine components, such as
low or no maternal antibodies at 6 weeks virus (FeLV) is considered noncore preservatives, adjuvants, or pH, can
contribute to local inflammation.2
Chronic inflammation has been
POSTINJECTION LUMPS: THE 3-2-1 RULE implicated as a potential factor in the
Most postvaccination lumps development of vaccine-associated
usually resolve within a few weeks. sarcomas (VAS).7 Although the precise
However, lumps that persist for more cause of VAS is not known, the AAFP
than 3 months after the injection, Feline Vaccine Advisory Panel suggests
are larger than 2 cm in diameter,
using less inflammatory products
or continue to increase in size
1 month after injection should be
investigated.5 In these cases, a Most products today are killed,
biopsy and chest radiographs can modified-live virus (MLV), or recombinant
help determine the diagnosis and canarypox-vectored vaccines. Killed virus
prognosis. Cats with vaccine-associated vaccines generally require an adjuvant to
sarcomas require aggressive treatment, bolster the immune response. Most MLV
and, if possible, injectable vaccines and recombinant feline vaccines, on the
should be discontinued in the future
other hand, are capable of stimulating
in these cats.5
an effective immune response without
Sponsored by an educational grant from Merial © 2009 Merial Limited, Duluth, GA. All rights reserved.
® VET JET is a registered trademark of Merial.
45. Primary Kitten Vaccine Series5
Vaccine Initial Dosea Booster Intervals Considerations
Feline panleukopenia As early as 6 weeks of age Every 3 to 4 weeks
Feline herpesvirus-1 As early as 6 weeks of age Every 3 to 4 weeks
Feline calicivirus As early as 6 weeks of age Every 3 to 4 weeks
Rabies As early as 8 weeks of age Single dose in the first year;
or 12 to 16 weeks of age follow state or local statutes
Feline leukemia virus As early as 8 weeks One booster 3 to 4 Kittens should test negative
(FeLV) of age weeks later for FeLV before vaccination
aDepends on the vaccine.
adjuvants. The canarypox-vectored a few weeks. However, a lump that 2006, pp. 1069–1119.
recombinant vaccines, for example, persists or grows can be a sign of VAS. 3. Dawson S, Willoughby K, Gaskell R, et al: A
field trial to assess the effect of vaccination
stimulate protective immunity and Although the risk of VAS is relatively against feline herpesvirus, feline calicivirus and
reduce the potential risks associated low (approximately one to two cases per feline panleukopenia virus in 6-week-old kit-
tens. J Feline Med Surg 3:17–21, 2001.
with an adjuvant. 10,000 vaccinated cats 8,9), the probability 4. Reese MJ, Patterson EV, Tucker SJ, et al: The
Another way to potentially reduce that a kitten will be exposed to a effect of anesthesia and surgery on serological
responses to vaccination in kittens. JAVMA
inflammation at the injection site is with potentially fatal disease is considerably 233(1):116–121, 2008.
the needle-free VET JET® transdermal higher.10 5. AAFP Advisory Panel: The 2006 American
delivery system. Compared with Still, vaccines are important, even for Association of Feline Practitioners Feline
Vaccine Advisory Panel Report. JAVMA
conventional needles and syringes, this indoor kittens. “It’s possible for owners 9(1):1405–1441, 2006.
system disperses a smaller volume of to track the panleukopenia virus into the 6. Hoover EA, Olsen RG, Hardy WD Jr, et al: Feline
leukemia virus infection: Age-related variation in
vaccine (0.25 ml) into the tissue through house,” according to Dr. Wolf, “and response of cats to experimental infection. J Natl
a tiny orifice (about the diameter of a 36- while less likely, owners can bring Cancer Inst 57:365–369, 1976.
gauge needle). respiratory viruses home on their 7. Macy DW, Hendrick MJ: The potential role of
inflammation in the development of postvacci-
clothing.”11 Kittens may also be exposed nal sarcomas in cats. Vet Clin North Am 26(1):
Discussing Vaccine Issues to sick cats through porch screens or 103–108, 1996.
with Clients when boarded, groomed, or traveling 8. Kass PH, Barnes WG Jr, Spangler WL, et al:
Epidemiologic evidence for a causal relation
Owners should be instructed to monitor with their owners. “Certainly, all kittens between fibrosarcoma and tumorgenesis in
their kittens for signs of possible vaccine need to receive their core vaccines,” says cats. JAVMA 203:396–405, 1993.
9. Esplin DG, McGill LD, Meininger AC, et al:
reactions. “The most common reaction Dr. Wolf. Postvaccination sarcomas in cats. JAVMA
is a mild malaise or fever that may last 202:1245–1247, 1993.
for 24 hours,” explains Dr. Wolf. “That’s REFERENCES 10. Tizard IR: The uses of vaccines, in Veterinary
1. Richards J, Rodan I: Feline vaccination guide- Immunology: An Introduction, St. Louis, Saun-
simply the immune system responding lines. Vet Clin North Am Small Anim Pract ders Elsevier, 2009, pp. 270−285.
to the vaccine.” (31)3:455−472, 2001. 11. Gaskell RM, Dawson S, Radford A: Feline respira-
2. Greene CE, Schultz RD: Immunophylaxis, in tory disease, in Greene CE (ed): Infectious Dis-
Mild swelling at the vaccine site may Greene CE (ed): Infectious Diseases of the Dog eases of the Dog and Cat, ed. 3. St. Louis,
also occur and generally resolves within and Cat, ed. 3. St. Louis, Saunders Elsevier, Saunders Elsevier, 2006, pp. 145−154.
This information has not been peer reviewed and does not necessarily reflect the opinions of, nor constitute or imply endorsement or
recommendation by, the Publisher or Editorial Board. The Publisher is not responsible for any data, opinions, or statements provided herein.
CE Immunosuppressive Therapy for Canine IMHA
56. Ryffel B. Experimental toxicological studies with cyclosporine A. anaemia and auto-immune thrombocytopenia purpura. Br J Hae-
In: White CE, White DJG, eds. Cyclosporin A. Amsterdam: Elsevier matol 2002;117:712-715.
Biomedical Press; 2003:45-75. 64. Mehling A, Grabbe S, Voskort M, et al. Mycophenolate mofetil
57. Blackwood L, German AJ, Stell AJ, O’Neil T. Multicentric lymphoma in impairs the maturation and function of murine dendritic cells. J Im-
a dog after cyclosporine therapy. J Small Anim Pract 2004;45:259-262. munol 2000;165:2374-3281.
58. Callan MB, Preziosi D, Mauldin E. Multiple papillomavirus-as- 65. Gregory CR, Stewart A, Sturges B, et al. Leﬂunomide effective-
sociated epidermal hamartomas and squamous cell carcinoma in ly treats naturally occurring immune-mediated and inﬂammatory
situ in a dog following chronic treatment with prednisone and cy- diseases of the dog that are unresponsive to conventional therapy.
closporine. Vet Derm 2005;16:338-345. Transplant Proc 1998;30:4143-4148.
59. Kuiper RAJ, Malingre MM, Beijnen JH, et al. Cyclosporine-in- 66. Cohen S, Cannon GW, Schiff M, et al. Two-year, blinded, ran-
duced anaphylaxis. Ann Pharmacother 2000;34:858-861. domized, controlled trial of treatment of active rheumatoid arthri-
60. Gummert JF, Ikonen T, Morris RE. Newer immunosuppressive tis with leﬂunomide compared with methotrexate. Arthritis Rheum
drugs: a review. J Am Soc Nephrol 1999;10:1366-1380. 2001;44:1984-1992.
61. Platz KP, Sollinger HW, Hullett DA, et al. RS-61443—a new, po- 67. Gregory CR, Silva HT, Patz JD, Morris RE. Comparative effects
tent immunosuppressive agent. Transplantation 1991;51:27-31. of malononitriloamide analogs of leﬂunomide on whole blood lym-
62. Dewey CW, Boothe DM, Rinn KL, et al. Treatment of a myasthenic dog phocyte stimulation in humans, rhesus macaques, cats, dogs, and
with mycophenolate mofetil. J Vet Emerg Crit Care 2000;10:177-187. rats. Transplantation Proc 1998;30:1047-1048.
63. Howard J, Hoffbrand AV, Prentice HG, Mehta A. Mycopheno- 68. Yokota S. Mizoribine: mode of action and effects in clinical use.
late mofetil for the treatment of refractory autoimmune haemolytic Pediatr Intl 2002;44:196-198.
CREDITS CE TEST 3 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 CompendiumVet.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 statement regarding dogs with of cyclophosphamide. b. increased risk of infection
IMHA is correct? c. Secondary malignancies have been c. bone marrow suppression
a. Most dogs die during the maintenance reported in dogs receiving cyclosporine. d. increased risk of thromboembolic
phase of disease management. d. Cyclosporine is a potent cytotoxic disease
b. All dogs can be successfully weaned off immunosuppressive drug.
immunosuppressive therapy. 8. Which patient is the most suitable candi-
c. Dogs that survive the ﬁrst 2 weeks of 4. Which statement regarding the mecha- date for hIVIG treatment?
the disease generally have a good long- nism of action of immunosuppressive a. a dog with a 3-day history of mild weak-
term prognosis. agents is incorrect? ness, a PCV of 26%, total bilirubin of 1.5
d. To avoid relapses, dogs should never a. Azathioprine is a competitive purine mg/dL, and 2+ spherocytes
be weaned off immunosuppressive antagonist. b. a dog experiencing an IMHA relapse
medications. b. Mizoribine blocks the purine biosyn- with PCV of 24% and a history of
thetic pathway. receiving an hIVIG dose 1 month earlier
2. Which statement regarding glucocorti- c. Leﬂunomide blocks the biosynthesis of c. a dog that has been hospitalized for
coid therapy for treating IMHA is correct? pyrimidine. IMHA for 3 days and received pred-
a. Prednisone at 2 mg/kg bid is a good d. Cyclosporine works by blocking the nisone 2 mg/kg bid and three blood
dose for large- and giant-breed dogs, biosynthesis of pyrimidine. transfusions
whereas small-breed dogs should not d. a dog presenting with acute IMHA, a
receive more than 1.2 mg/kg bid. 5. Which is not a reported side effect of PCV of 20%, and a history of conges-
b. It has been proven that dexamethasone cyclosporine therapy in dogs? tive heart failure
is superior to prednisone for inducing a. GI disturbances
remission. b. infection 9. Which immunosuppressive therapy
c. Dexamethasone is not appropriate for c. development of secondary neoplasia is unlikely to be effective in the ﬁrst 2
alternate-day therapy. d. aplastic anemia weeks of treating IMHA?
d. Prednisone at doses higher than 2 a. glucocorticoids c. azathioprine
mg/kg bid is associated with better 6. Which is not a side effect of azathioprine b. splenectomy d. hIVIG
outcomes. therapy in dogs?
a. pancreatitis 10. In dogs with IMHA, administration of
3. Which statement regarding immunosup- b. bone marrow toxicity which immunosuppressive drug has
pressive agents used to treat canine c. gingival hyperplasia been associated with a worse outcome
IMHA is correct? d. GI disturbances in retrospective studies?
a. Azathioprine is a good drug to induce a. cyclosporine
remission, but it can cause bone mar- 7. Which is not a side effect of b. leﬂunomide
row suppression. glucocorticoids? c. cyclophosphamide
b. Hepatotoxicity is a common side effect a. GI ulceration and perforation d. mycophenolate mofetil
44 Compendium: Continuing Education for Veterinarians® | January 2009 | CompendiumVet.com
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CompendiumVet.com | January 2009 | Compendium: Continuing Education for Veterinarians® 45
49. DIET HISTORY FORM
Date: _______________________________________________ Stamp clinic information below:
Case Number: ________________________________________
Email address: ________________________________________
Phone (home): ________________________________________
Best time to call:_______________________________________
Is food left out for your pet during the day? ❏ Yes ❏ No
Name: __________________________________ Age: ________
Does your pet have access to other, unmonitored food sources
Species: _____________________ Breed: ___________________
Gender: ❏ Male ❏ Female Neutered/spayed: ❏ Yes ❏ No (e.g., treats fed by neighbor, food left for outdoor cats)?
Current weight: _____________ Usual weight: _____________ ❏ Yes ❏ No
Body condition score (1–9): _____ If yes, please describe:________________________________
Evidence of muscle wasting ❏ None ❏ Mild ❏ Severe ____________________________________________________
Reason for Visit ____________________________________________________
____________________________________________________ If you have more than one pet, do they have access to each other’s
____________________________________________________ food? ❏ Yes ❏ No If yes, please describe:
How many adults are in your household? ___________________
How many children are in your household, and how old are they?
How do you store your pet’s food? ________________________
Where is your pet housed? ❏ Indoors ❏ Outdoors ❏ Both
Do you have other pets? ❏ Yes ❏ No If so, please list species ____________________________________________________
and specify if they live indoors or outdoors. ____________________________________________________
How active is your pet?
❏ Hyperactive ❏ Very active ❏ Average
❏ Not very active ❏ Hardly moves
Feeding Management How often is your pet walked?
Who typically feeds your pet? ____________________________ ❏ At least 3 times/day ❏ 1-2 times/day ❏ Once a day
____________________________________________________ ❏ Seldom ❏ Never
____________________________________________________ Do you have access to a yard? ❏ Yes ❏ No
When is your pet fed? __________________________________ Is it difﬁcult to exercise your pet? ❏ Yes ❏ No
____________________________________________________ Can exercise be increased? ❏ Yes ❏ No
____________________________________________________ Has your pet participated in training? ❏ Yes ❏ No
____________________________________________________ Has your pet participated in competition? ❏ Yes ❏ No
©2009 Veterinary Learning Systems
50. DIET HISTORY FORM
Behavior Table foods or scraps; home-prepared foods
How does your pet act toward food? ____________________________________________________
❏ Greedy ❏ Indifferent ❏ Shows avoidance ____________________________________________________
Has your pet’s attitude toward food changed? If so, describe: ____________________________________________________
____________________________________________________ Dietary supplements; food used to give pills
If you have other pets, is this pet dominant or submissive to them? ____________________________________________________
❏ Dominant ❏ Submissive ____________________________________________________
Has your pet recently lost or gained weight? If so, please describe: ____________________________________________________
____________________________________________________ List anything else given by mouth (e.g., medications):
Have there been any recent changes in activity level? __________ ____________________________________________________
Have you observed any of the following:
Is your pet’s current diet a change from its typical diet?
Nausea/salivation ❏ Yes ❏ No
❏ Yes ❏ No
Difﬁculty chewing ❏ Yes ❏ No
If so, please describe the change and why the diet was changed.
Difﬁculty swallowing ❏ Yes ❏ No
Vomiting ❏ Yes ❏ No ____________________________________________________
Diarrhea ❏ Yes ❏ No ____________________________________________________
Constipation ❏ Yes ❏ No ____________________________________________________
Have there been any changes in urination? ❏ Yes ❏ No ____________________________________________________
Are you open to making a change in your pet’s diet?
For each of the following categories, list the brand names (if appli-
cable) and amounts of all foods your pet eats daily, as well as how ❏ Yes ❏ No
often each food is fed (e.g., twice a day). What are your pet’s food preferences?______________________
Commercial foods ____________________________________________________
____________________________________________________ What foods does your pet refuse? _________________________
Commercial treats; dental hygiene products ____________________________________________________
____________________________________________________ Are there foods to which your pet is allergic? ❏ Yes ❏ No
____________________________________________________ If so, which foods? ____________________________________
©2009 Veterinary Learning Systems
51. Raising the
level of care
“AAHA is continually looking for ways to help
member practices run better. AAHA endorses
Vetstreet because it offers clinics an important
client outreach tool. The Vetstreet Pet Portal® service
allows us to better connect with and educate
our clients, increase compliance and,
most importantly, raise the level of
health care for our patients. ”
Anna Worth, DVM
2008-2009 AAHA President
West Mountain Veterinary Hospital
Easy to set up and easy to use, Vetstreet™ is a powerful practice communication and
management tool that keeps you in touch with your clients via Pet Portals. To discover how
Vetstreet can help you increase client satisfaction, build compliance, and enhance your
bottom line, visit Vetstreet.com, call toll-free 888-799-8387 or email firstname.lastname@example.org.
Visit us at NAVC/Booth #927and WVC/Booth #1951
Vetstreet is a trademark of VetInsite.com, Inc. Pet Portal is a registered trademark of VetInsite.com, Inc.
52. Month-long ﬂea protection
in a chewable tablet
Fast-acting Convenient Family-friendly Doesn’t wash off
• Starts killing ﬂeas in 30 minutes
• 100% effective within 4 hours
in a controlled laboratory study
• Approved by the FDA and
available by prescription only
To learn more about Comfortis®, see your Lilly representative or
distributor representative, call 1 (888) LillyPet or visit www.comfortis4dogs.com
The most common adverse reaction recorded during clinical trials was vomiting. Other adverse reactions were decreased
appetite, lethargy or decreased activity, diarrhea, cough, increased thirst, vocalization, increased appetite, redness of the
skin, hyperactivity and excessive salivation. For product label, including important safety information, see page 46.
©2009 Eli Lilly and Company CF00305 010109