PURINA Pro Club
German Shepherd Dog Update
Vol. 7, No. 1
■
June 2008
Research Focuses on Genetic Basis of Perianal Fistula
arolyn Lavengood found the
perfect canine companion in
her first German Shepherd Dog,
Kinderheim’s Kandi-Ana Angel, CGC.
She and “Kandi” became good friends
at puppy socialization classes and
later at canine obedience training.
Though Lavengood had no intention
of showing Kandi in conformation, the
shepherd’s sire was a conformation
champion, and the dam came from a
police canine line. When Kandi was
2 ½ years old, Lavengood noticed
she frequently licked her bottom and
struggled to defecate. At first, she
thought it could be related to impacted anal glands; Kandi went monthly
to the veterinarian to have the glands
expressed. Then, Lavengood noticed a
near-perfect circle of tiny pin holes
around Kandi’s rear end.
As it turned out, Kandi was diagnosed with anal furunculosis, more
commonly known as perianal fistula
(PAF). A chronic, progressive, inflammatory condition, perianal fistulas
occur in several breeds, but German
Shepherd Dogs make up about 90
percent to 95 percent of cases. Though
the majority of affected dogs are 7 years
old or older, the condition has been
reported in puppies as young as 6 to
8 months old. Perianal fistulas also
occur in humans with Crohn’s disease.
A painful disease, PAF can become
inflamed and raw from dogs constantly
licking. Infection oozes from tiny pin
holes, which actually are fistulous
tracts, or tubelike structures that the
body creates for the infection to drain.
The thick, bushy tail of the German
Shepherd Dog is believed to aggravate
the condition by keeping the area moist.
Adding to owners’ frustrations, dogs
emanate a constant odor. Sadly, some
owners have had to euthanize affected
dogs due to chronic problems.
In 1993, when Kandi was diagnosed
with perianal fistulas, Lavengood, who
lives in Lexington, Ky., learned about
an experimental treatment involving
prednisone, a steroid, developed by
veterinarians at Michigan State University. She was eager to try it, so her
veterinarian contacted the Michigan
State veterinarians to learn the pro-
C
tocol. At first, Lavengood could not
believe the required dosage.
The first two weeks of treatment
were the most intense. Dogs were given
one milligram of prednisone per pound
of body weight. Kandi, who weighed
80 pounds, received 80 milligrams.
The dosage was reduced to half over
the next four weeks. Eventually a
Signs of Perianal Fistula
erman Shepherd Dogs
account for 90 percent to
95 percent of reported cases of
perianal fistula, although the
condition has been identified in
many other breeds. Owners
should be aware of signs of this
condition as early diagnosis and
treatment can help to improve a
dog’s prognosis.
Among common signs are:
• Licking and biting the anal area;
• Difficulty defecating;
• Behavioral changes, such as
lethargy and anorexia;
• Anorexia, or prolonged loss
of appetite;
• Depression; and
• Diarrhea.
G
maintenance level was determined.
“We were never able to get the
prednisone down to an acceptable
level,” Lavengood recalls. “When the
level became too low, the fistulas began
festering again. All along Kandi experienced terrible side effects. She thought
she was starving to death and was
always thirsty. She developed puppy
mange and had bare spots on her coat.
She experienced a staph infection,
muscle wasting and was depressed.
She totally was not herself.”
After 10 months of prednisone
treatment, Lavengood decided to take
Kandi off the steroid and try surgery.
Though the surgery was not guaranteed to work, it offered hope. The twoand-a-half-hour procedure involved
the veterinarian excising the diseased
tissue and cauterizing the fistulous
tracts. Risks included possible scar
tissue, damage to the sphincter muscle
that could lead to incontinence, and
stenosis, or narrowing of the anus.
Following surgery, “the veterinarian
told me if Kandi made it six months
without perianal fistulas, she had a
good chance they would not recur,”
says Lavengood.
With her bottom full of surgical
staples, Kandi went home, where she
received optimal care from Lavengood.
Indeed, the PAF did not return. In fact,
after her anal glands were removed a
few months later, Kandi never had
another surgery the rest of her life.
She died in June 2004 at age 13 ½.
The lessons learned from the
experience prompted Lavengood in
1998 to organize an online support
group to help others. She serves as
moderator of the PAF chat room that
today has 458 members worldwide.
Study Involves Genome Scan
One investigator has a keen interest
in discovering the genetic aspects of
perianal fistulas. Lorna Kennedy, Ph.D.,
senior scientist at the University of
Manchester Centre for Integrated
Genomic Medical Research in the
United Kingdom, has received an AKC
Canine Health Foundation grant to
examine genes potentially associated
with PAF. She is conducting a genomewide scan looking for variations in the
DNA sequence that are potentially
associated with perianal fistula.
“The prevalence of this disease in
German Shepherd Dogs suggests a
genetic predisposition,” Kennedy says.
“Their high risk for PAF is almost
certainly due to the presence of a
particular gene or several genes acting
together at high frequency,” she says.
“Because cyclosporine, an immunosuppressant, is effective in treating
this disease, we believe an immunemediated pathogenesis exists.”
The research team has studied
canine major histocompatibility complex (MHC) immune response genes
in 107 German Shepherd Dogs with
perianal fistulas and 196 unaffected
German Shepherd Dogs. They also
looked at a second smaller group of
Continued on page 2
Perianal Fistula
PAF Support Group & Web Site Available
continued from page 1
German Shepherd Dogs from Finland
consisting of 12 diagnosed with PAF
and 15 with various other diagnoses.
A breakthrough came when the
investigators discovered a strong
association between one particular
gene variant in the major histocompatibility complex and perianal fistula.
The MHC is known to play a part in
determining the susceptibility of dogs
to several immune-mediated diseases,
such as rheumatoid arthritis, hemolytic
anemia, lymphocytic thyroiditis, and
even diabetes.
“The association confirms there is
a partly genetic basis for this disease
that is likely to have an autoimmune
component,” says Kennedy. “However,
since not all German Shepherd Dogs
carrying this particular variant devel-
“THE
ASSOCIATION CONFIRMS
THERE IS A PARTLY GENETIC BASIS
FOR THIS DISEASE THAT IS LIKELY
TO HAVE AN AUTOIMMUNE
COMPONENT.
NOT ALL
HOWEVER,
SINCE
GERMAN SHEPHERD DOGS
CARRYING THIS PARTICULAR VARIANT
DEVELOP PERIANAL FISTULAS, THE
LIKELIHOOD IS THAT THERE ARE
OTHER GENES INVOLVED IN DISEASE
DEVELOPMENT, AS WELL AS A
POSSIBLE ENVIRONMENTAL TRIGGER.”
LORNA KENNEDY, PH.D., SENIOR SCIENTIST AT THE
UNIVERSITY OF MANCHESTER CENTRE FOR
INTEGRATED GENOMIC MEDICAL RESEARCH
IN THE UNITED KINGDOM
op perianal fistulas, the likelihood is
that there are other genes involved
in disease development, as well as a
possible environmental trigger. Thus,
a dog will have to carry particular
variants at several different genes in
order to develop the disease.”
The results of the whole genome
scan currently are being analyzed.
The investigators are optimistic that
the scan will indicate several areas of
the genome that are associated with
the disease. These areas will then be
targeted for further research to identify the genes that may contribute to
the disease development.
Meanwhile, Kennedy advises breeders to avoid breeding dogs with the
condition, especially dogs that develop
the disease at an early age. If a genetic basis could be found for perianal
fistulas and a genetic test developed,
breeders could potentially selectively
breed dogs that would not produce
affected offspring.
wners whose dogs have been diagnosed with perianal fistula (PAF)
can visit http://groups. yahoo. com to find an online support group.
Carolyn Lavengood, whose German Shepherd Dog “Kandi” was diagnosed
with PAF in 1993, moderates the chat room.
Additional information on PAF can be found at this Web address:
http://members.tripod.com/~perianal-fistulas/MainIndex.html.
O
Disease Management
Until a test is available, veterinarians
continue to work to improve treatment
and surgical options for affected dogs.
Since Kandi received treatment for
PAF in 1993, cyclosporine has been
discovered as an effective, although
expensive, treatment option. This medication was known to help humans
with Crohn’s disease who develop
perianal fistulas and was likewise
found to benefit dogs.
Researchers at the University of
Wisconsin School of Veterinary Medicine found that cyclosporine effectively resolved or reduced perianal fistula
in 25 of 26 dogs they studied. Robert
Hardie, D.V.M., assistant professor of
surgery at the University of Wisconsin,
says, “We now largely treat canine
perianal fistula with a combination
of cyclosporine and ketoconazole, a
drug given to slow down the metabolism of cyclosporine. Our approach
to treating this disease has changed
dramatically over the last several years
with the success of cyclosporine therapy, and we rarely recommend surgery
as a ‘first line of treatment.’
“Unfortunately, recurrence of PAF
after an initial course of cyclosporine
treatment is still relatively high, and
many dogs require long-term or maintenance therapy to control the disease,”
Hardie says. “For these dogs, the goal
of treatment is to minimize the clinical
signs and extent of the lesions with
the least amount of cyclosporine
possible, similar to how humans with
Crohn’s disease are managed throughout their lives.”
Rod Rosychuk, D.V.M., associate
professor of dermatology at Colorado
State University College of Veterinary
Medicine, agrees. “Surgery is seldom
used today,” he says. “This is because
medical management using cyclosporine largely has been more successful
than surgery.”
A wide variety of cyclosporine
dosages and dosage regimens are
used. “We typically begin at a higher
level and then reduce the dosage
gradually once the maximal degree
of benefit is achieved,” Rosychuk says.
“Once individuals go into remission,
the drug can eventually be stopped in
some individuals. In others, perianal
fistulas recur as the cyclosporine is
reduced, and the dog must be returned
to a higher dose to control the problem.
Long-term maintenance therapy may
be required.”
Besides the cauterization surgery
that Kandi received, other surgical
techniques include electrosurgery,
2
laser surgery and surgical excision.
“All have potential postoperative
complications such as PAF recurrence,
anal stricture formation, fecal incontinence, and difficulty defecating,”
says Hardie. “In other words, all of
these surgical procedures involve some
risk that is generally avoided with
cyclosporine therapy.”
Kandi was one of the lucky German
Shepherd Dogs whose surgery did
successfully manage PAF and who went
on to live a long life. Lavengood has
continued to stay involved as moderator
of the online PAF chat room. She now
lives with two German Shepherd Dogs,
neither having experienced perianal
fistulas. Lavengood is optimistic that
Kennedy and the United Kingdom
research team will eventually unravel
the genetic mystery about the disease.
“Perianal fistula is a horrible condition to go through with your dog,”
Lavengood says. “Kandi and I were
handed a bunch of lemons, and we
tried to make lemonade. I think we
are on the brink of some major discoveries that will help breeders and
owners everywhere.” ■
Purina appreciates the support of
the American German Shepherd
Dog Charitable Foundation and
particularly Ginny Altman, AGSDCF health liaison and immediate
past president of the German
Shepherd Dog Club of America
Inc., in helping to identify topics
for the Purina Pro Club German
Shepherd Dog Update newsletter.
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