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Health Issues:
Written by: Jeff Vidt, DVM
Familial Shar-Pei Fever
Familial Shar-Pei Fever (FSF) is a hereditary inflammatory disorder seen in
Shar-Pei. It is inherited as an autosomal recessive condition.
Clinical signs:
Episodic fever is the most important and consistent clinical sign of this disorder.
The temperature commonly is in the 105-107°F range. The fever is generally
self-limiting lasting 12-36 hours. Another common clinical sign often
accompanying the fever is swelling of a joint, usually the hock (tibiotarsal) joint
and is known as Swollen Hock Syndrome (SHS). This painful, hot swelling can also
involve the carpus (wrist) and the lips. Dogs with FSF are sick -- they are reluctant
to move and when they do walk they have a characteristic "walking on eggs" gait.
They often are painful in the abdomen and have a characteristic "roached" back.
Pathogenesis:
What we do know about this disease is as follows:
- Shar-Pei with FSF have increased levels of the cytokine Interleukin-6 (IL-6).
IL-6 is involved with the fever response and and is an integral part of triggering
the production of Acute Phase Reactant Proteins by the liver. IL-6 is also
involved in the Systemic Inflammatory Response Syndrome (SIRS). Dysregulation
of IL-6 is the cause of much of the disease in Shar-Pei with FSF. IL-6 also
plays a major role in the body's stress response and serves to "prime" the
immune system.
- Shar-Pei with FSF are at risk from early death from systemic amyloidosis.
About 25% of the FSF dogs will develop renal failure including renal amyloidosis --
a smaller percentage will develop hepatic amyloidosis. This is usually seen in
Shar-Pei between the ages of 2-5 years of age. They also seem more susceptible
to immune-mediated kidney disease such as membranous glomerulonephritis,
protein-losing glomerulopathies, DIC, thromboembolic phenomena such as mesenteric,
splenic and pulmonary embolism and Streptococcal Toxic Shock Syndrome (STSS).
- FSF in Shar-Pei was hypothesized to be an animal model of Familial
Mediterranean Fever (FMF) in humans. Recent work indicates this is not true, although
FSF is very similar to FMF in man.
- FSF is a heredofamilial disease with a genetic basis. It appears to be inherited
as an autosomal recessive condition.
Laboratory Findings:
Unfortunately there are no blood test, etc. which are
specific for FSF. During a fever episode there will often be an increased white
blood cell count, an increase in liver enzyme levels and other non-specific findings.
Work done by Dr. Gary Johnson at the University of Missouri College of Veterinary
Medicine to develop a DNA blood test to screen for the disease was unsuccessful and
the research effort will still continue.
Treatment:
It is very important to monitor the temperature in this condition.
Initially, fever can be treated using aspirin. Usually a regular strength adult aspirin
is given every 6 hours for the first 24 hours and then twice a day for 3-5 day
thereafter. In rare cases where aspirin doesn't work of for extremely high fevers,
dipyrone is given. Some patients will require supportive care with intravenous fluid
therapy and in extreme cases emergency treatment similar to heat stroke treatment.
Antibiotics are not normally indicated in this condition.
Colchicine:
Colchicine is a drug that has been in use in people with FMF to prevent
amyloidosis. It is currently being recommended in Shar-Pei with FSF for the same
purpose. No studies have been completed to determine if it is useful for this purpose
in the Shar-Pei or not. The clinical impression is that it does help. Those dogs on
colchicine seem to have fewer FSF episodes and less severe signs while on the drug.
Side-effects appear to be minimal at this time and are primarily gastrointestinal
such as vomiting, diarrhea, anorexia (decreased appetite), etc.
Prevention:
Shar-Pei with FSF only show symptoms sporadically. It would appear
that there are "triggers" involved in initiation of the FSF episodes. One of the major
triggers appears to be stress. This may be a dog training class, a dog show, another
illness, a dog in heat, excessive exercise, etc. If the owner can recognize these
triggers and take steps to avoid them the number of FSF episodes can often be
reduced. Diet does not appear to be helpful in prevention of FSF or kidney disease.
Surely diet has a role in the management of the kidney disease once clinical signs are
apparent. Low dose aspirin therapy may be useful in decreasing the incidence of
FSF and its severity as well. Aspirin may also be useful as an adjunct therapy in the
prevention of thromboembolism.
Monitoring:
Monitoring for the complications which often accompany FSF is one of the
major goals of the owner of an FSF dog. The primary and most consistent
sequela to FSF is kidney failure either due to immune-mediated kidney disease or renal
amyloidosis. I currently recommend monitoring a urinalysis every 3 months. The sample
should be collected first thing in the morning after the water has been taken up overnight.
I primarily look at the urine specific gravity which is a measure of the concentration of the
urine and the protein levers in the urine. When the kidneys begin to fail the initial
indication is a loss in the ability to produce a concentrated urine. This occurs before
there are blood changed related to kidney failure. Increased water consumption,
increased urination are the clinical signs associated with the loss of concentrating
ability, but these signs are often not recognized. I also thing it is wise to do a blood
panel every 6-12 months and certainly do one in the urinalysis is abnormal. Weighing
your dog periodically is very important. We often don't recognize a significant weight
loss because it is very subtle over a longer period of time. Water consumption and appetite
are other important indicators to watch.
Complications of FSF:
We have already discussed the kidney complications in this condition. Other
Complications which have been documented include thromboembolism
(mesenteric, splenic, pulmonary), DIC (disseminated intravascular coagulation),
SIRS (systemic inflammatory response syndrome), MODS (multiple organ dysfunction
syndrome), STSS (streptococcal toxic shock syndrome), hypertension associated with
renal failure. Many of the deaths following an acute FSF episode are due to these
complications. No FSF episode should be treated lightly!
Diagnosis:
There is no specific diagnostic test for FSF at this time. Diagnosis is based
on the clinical sign of episodic fever in a Shar-Pei. I think every Shar-Pei that
dies should be autopsied to determine the cause of death, but this is even more
critical in cases involving FSF. Renal amyloidosis can only be diagnosed based on
kidney biopsy and staining with Congo Red stain. This stain is specific for the
presence of amyloid. Amyloid has been found in other tissues in Shar-Pei as well
so special staining should be requested on all tissues submitted for histopathology.
Many dogs with FSF will not have amyloid in the tissues at the time the tissues
were harvested -- this means the absence of amyloid in a biopsy specimen does not
mean that dog will not or would not have gone on to develop amyloidosis at a later time.
To further confuse the issue, not all Shar-Pei with amyloidosis have shown signs of FSF.
Future:
Research is currently underway at the University of Missouri College of Veterinary
Medicine by Dr. Gary Johnson to develop a DNA blood test. The gene for human
FMF was sequenced in the Fall of 1997 and with that information Dr. Johnson had
hoped to sequence the FSF gene. That information was applied by Dr. Gary Johnson to
FSF in a research project founded by the CSPCA Charitable Trust. That project did
determine that the mutations causing FMF in man do not exist in FSF in the Shar-Pei,
hence they are two distinct, although similar diseases. There are other hereditary
inflammatory fever disorders in man and Dr. Kastner ant the National Institutes of
Health are looking at the disorder with information supplied by Dr. Tintle. Familial
Hibernian Fever in man has also been ruled out as the cause of FSF by Dr. Johnson
with information supplied by NIH. Work will continue to find the genetic mutation(s)
responsible for FSF in Shar-Pei.
As of this writing the mutation responsible for FSF has not been found. If a test can be
developed, a screening program can be established to screen breeding stock and
determine normal individuals, carriers and affected dogs. With this information Shar-Pei
breeders can gradually eliminate this genetic disease from the breed. One of the major
obstacles to research revolves around the unpredictable phenotype of FSF. There is
no consistent age range when clinical signs develop, the clinical signs can be variable,
some dogs develop amyloidosis, some don't, etc. This makes it very difficult to use
genetic selection methods which are based on phenotype.
Recommendations:
All Shar-Pei with FSF should be on colchicine and be regularly monitored via urine
samples and blood work for development of complications. Dogs with FSF should not be
used in breeding programs and should be neutered. Dogs with a family history of FSF
should be on colchicine and monitored. Dogs with FSF should be maintained as
stress-free as possible.