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Familial Shar-Pei Fever and Familial Amyloidosis of Chinese Shar-Pei
Dogs
Linda J.M. Tintle, D.V.M.
Shar-Pei with Familial Shar-Pei Fever (FSF):
* Have
one or more bouts of unexplained fever, usually 103-107 degrees F
(39.4-41.7 degrees C) but rare cases may go higher.
* If
they do not have a fever, it is
not FSF. (Assuming not
on colchicine).
* Fevers
usually start before they are 18 months old but adult-onset attacks are
not uncommon. Fever episodes usually become less frequent with age.
* Fever
episodes last 24-36 hours in most cases without treatment.
*
Of the dogs that experienced fevers, approximately
53% had experienced
Swollen Hock Syndrome (SHS)
at some time along
with the fever.
*
Be very careful not to mistake the normal “socks” (excess wrinkling
around the hocks on some Shar-Pei) for SHS.
*
One or more of the following signs may accompany fever episodes:
* Swelling around a joint (cellulitis) with or without
inflammation of the joint itself. One or more joints may be affected
but most cases involve the tibiotarsal or hock joint (SHS).
* Sometimes a swollen painful muzzle.
* Abdominal pain, reluctance to move, “roached” back, mild
vomiting or diarrhea, shallow rapid breathing.
Familial Mediterranean Fever (FMF) vs. FSF - FMF is:
* An
autosomally recessive inherited periodic fever disorder of humans. The
hereditary fever syndromes are inherited disorders characterized by
self-limited episodes of fever with inflammation of joint or body cavity
linings without any apparent infectious cause.
* Characterized
by recurrent bouts of fever, usually starting in childhood.
* Polyserositis
(inflammation of the thin membranes that line certain cavities of the
body... joints, abdomen, chest, etc.) resulting in abdominal, chest and
joint pain, usually involving the knee or ankle.
* Swelling/inflammation
of the skin about the ankles or top of the foot.
* Free
from symptoms between attacks.
* May
develop amyloidosis.
Shar-Pei with FSF have abnormally high resting levels of a cytokine
called Interleukin-6 (IL-6).
* IL-6
turns on various parts of the immune system. It is involved in
controlling the fever
response and is a trigger, alone or with other cytokines, for the
production of the acute phase reactant proteins (APP) of inflammation...
the precursors of Amyloid AA. Chronically elevated levels of IL-6 and
other cytokines lead to chronically elevated levels of the APP.
* The
APP are normally
produced during active inflammation. The healthy animal breaks down the
APP soon after the injury or disease and the toxic wastes are excreted
from the body.
* Amyloidosis
occurs when the APP cannot be broken down normally by the animal because
of a defect in metabolism or when a large amount of APP continuously
overwhelms the body’s ability to get rid of it. Amyloid is then
deposited outside the cell walls and not eliminated from the body. The
build-up of the waste product amyloid is what causes the disease.
Amyloid may be detected in many different organs and in blood vessels.
In the kidneys, the damage is irreversible and usually results in
kidney failure
and subsequent death of the dog.
FSF is an
autoinflammatory disease characterized by dysregulation of the normal
paths of inflammation.
Inheritance of FSF and Amyloidosis in Chinese Shar-Pei.
* Published
research indicates that this trait is compatible with an autosomal
recessive inheritance. (AL Rivas, L Tintle, JM Scarlett, CP van Tassel,
& FW Quimby Journal of Heredity
1993; 84:438-442.)
* My
personal opinion, based on my experience and pedigree analysis, is that
heterozygous carriers may (or may not) experience fevers +/- SHS but do
not die prematurely from amyloidosis. I believe the homozygous animals
(which usually
but not always experience fevers +/- FSF) are the ones dying prematurely
from amyloidosis. There is evidence that environmental influences are
also important in whether or not an at-risk individual develops
amyloidosis.
* Private
communication with many of the original breeders and importers of these
dogs has led me to believe that many of these imported foundation dogs
were affected by this immune system dysregulation. Since all lines go
back to this same small genetic
pool of dogs, it is not surprising that the problem is
widespread throughout the breed and throughout the world.
-
In people with
“Phenotype II” FMF, signs of amyloidosis may precede outbreaks of
fever or the patient may never experience or report any fever.
-
Fever episodes
should be considered to be
an important marker
that the dog is at extremely
high risk to
develop amyloidosis and should be carefully monitored BUT not all
FSF patients will develop amyloidosis.
Amyloidosis>>> kidney failure or, less commonly, liver disease/ failure.
Amyloidosis is a killer.
* Deaths
have been reported to me as young as 8 months of age and as old as 12
years of age. It most commonly strikes between 3 and 5 years of age.
* Amyloidosis
can only be
diagnosed by surgical biopsy or by tissues obtained at autopsy. The
abnormal amyloid protein is identified with special stains when examined
under the microscope.
Frequency of FSF.
* A
survey done at the 1991 CSPCA National Specialty and data from records
at my own and Dr. Jeff Vidt’s practice suggests that the incidence of
FSF in Shar-Pei is about 23-28% affected. I believe the incidence may
be higher now.
How is
FSF diagnosed?
* No
single test is yet available
* Still
a clinical diagnosis by history, signs and excluding the other
possibilities.
* Blood
tests are usually negative/normal except that an elevated white blood
count with a left shift is not uncommon as is mildly elevated alkaline
phosphatase levels.
I
perform the following minimum database on patients with possible FSF and
then at least annually thereafter:
* Complete
blood count (CBC) with differential, serum chemistry panel, and complete
urinalysis (UA) on a first morning urine sample.
I also
routinely recommend these tests on all bitches prior to breeding and
studs at least annually! There are few worse horrors for a breeder than
having the stress of pregnancy cause a bitch to go into kidney failure
and die before the pups are a few weeks old and then having to raise a
litter of orphan puppies which you
know
are carrying the gene for amyloidosis.
* Lyme
Disease (Borreliosis) and other tick borne diseases should be ruled out
in endemic areas.
* If
UA suggests an increased amount of protein is being lost in the urine, I
recommend a urine protein to creatinine ratio be run on the urine. Most
affected Shar-Pei have medullary amyloid and may or may not have
proteinuria (unlike humans) but proteinuria is always a significant
finding. Loss of ability to concentrate urine (specific gravity
consistently 1.010 to 1.022) is a more common early indicator of a
problem.
* Immune
panels, joint taps, radiographs, cultures, immunoglobulin levels, and
other diagnostic procedures are sometimes needed in individual cases.
Treatment of FSF episodes.
* Tender
loving care, close observation of body temperature and otherwise benign
neglect.
* Buffered
aspirin.
* 1.0
ml of 50% Dipyrone SQ, or Banamine (flunixin meglumine) to reduce fever
and provide pain relief, particularly for fevers > 105 degrees.
* Extremely
high fevers or other systemic inflammatory response syndrome (SIRS) may
indicate that rapid aggressive iv fluid therapy and shock treatment is
necessary in some very rare
cases. FSF episodes
can be fatal and should
never be
shrugged off as inconsequential.
* There
is no infection
and therefore, antibiotics are unnecessary unless the veterinarian is
concerned that the stressed dog may be secondarily infected.
-
Recently, a few
cases of severe pustular dermatosis with high fevers and vast
sloughing of skin have been reported to or seen by Dr Jeff Vidt and
I. These seem to resemble the “flesh eating” Streptococcus
infections reported in humans and require aggressive antibiotic and
supportive treatment. These can be fatal even with treatment. A
recent report suggested that this is an immune mediated vasculitis
and steroids +/- azathioprine may be indicated. I have seen most
of my cases of this start with a “routine” FSF episode which for
some unknown reason triggers the immune mediated vasculitis and
sloughing.
Colchicine.
* Used
in humans for over 3000 years and most commonly used as a treatment for
gout.
* Used
in FMF patients to reduce the frequency and severity of painful fever
episodes and prevent the development of amyloidosis.
* Before
colchicine therapy, up to 30% of all FMF patients died prematurely
(usually around age 40) of amyloidosis.
* I
currently recommend the use of colchicine prophylactically in any
Shar-Pei that I believe to have FSF as soon as I am convinced of my
diagnosis. I do not
recommend waiting until evidence of disease due to amyloidosis is seen.
At that point, it is almost to late.
* We
have had some Shar-Pei on colchicine for over 7 years and I have yet to
see evidence of any serious side effects other than gastrointestinal
disturbances (diarrhea +/- vomiting) which resolve when the drug is
withdrawn. Some dogs are, however, unable to tolerate the drug because
of associated diarrhea. Others seem to tolerate a reduced dosage.
* In
FMF treatment, the drug has been shown to be
safe in children as
young as 3 years of age, in pregnant women, and when given lifelong.
Fatalities associated with massive overdoses have been due to bone
marrow suppression. I have monitored CBC’s in my patients and have not
seen evidence of bone marrow suppression but this should always be kept
in mind.
* I
recommend once daily treatment with 0.025-0.03mg/kg for 2 weeks
and if no gastrointestinal problems have occurred, I double the dose to
twice daily. For your average Shar-Pei, this is one 0.6 mg tablet
twice daily. I will provide a lengthy treatment protocol with
pertinent scientific references to any veterinarian upon request.
* I
personally believe that this
drug works in this disorder and is the best treatment
option currently available. I would like to see double-blind
controlled studies done to prove this but, so far no research has been
conducted or funded.
-
Dogs on colchicine
may continue to experience some fever episodes. Some cease
completely. Others commonly report a decrease in severity and
frequency. Some owners report SHS without fever. I believe the
colchicine works in dogs as it does in people: the control of fevers
and the blocking of amyloid deposition are by two different pathways
and on-going fevers are not
evidence of worsening amyloidosis.
-
There is
no association between the number, frequency and severity of the
episodes and the development or degree of amyloidosis.
A dog
that experiences one single fever episode in his entire life is just
as likely to get amyloidosis as the dog that gets them every 7-10
days. Any fever episode typical of FSF should be considered a
marker that the patient is at high risk for amyloidosis. This is
also why I do not recommend waiting to see if they ever get another
episode before starting colchicine!
Most
Common Signs of Advanced Amyloidosis.
* Unexplained
weight loss.
* Increased
thirst and frequency of urination.
* Vomiting
* “Bad
Breath” as a result of uremia (the buildup of toxins/wastes in the
bloodstream as the kidney +/- liver fails to process them).
How is
Amyloidosis Treated?
* Slow
the progression of irreversible kidney disease with dietary management
and supportive care... prescription kidney diets, omega 3 fatty acids,
low dose aspirin therapy, ACE-inhibitors (benazepril or enalapril), and
antioxidants may be indicated in individual cases.
* Thromboembolism
“throwing a clot” is not uncommon in these patients and is why low dose
(1/4 of a baby aspirin once daily) may be recommended.
* Liver
disease often shows up as severe jaundice along with weight loss,
vomiting and inappetance. These cases seem to have a better prognosis
than those primarily affecting the kidneys and have shown good response
to colchicine therapy with survival times over 4 years possible.
Other
causes of kidney failure in Shar-Pei (or... Why you need to get the
biopsy/necropsy specimens).
* Glomerulonephritis
* Pyelonephritis
* Renal
Infarcts
You
cannot assume that every Shar-Pei that died of kidney failure had
amyloidosis.
It is, however, the overwhelming cause of premature death in the breed.
Linda
J.M. Tintle, D.V.M.
Wurtsboro Veterinary Clinic, P.C.
163 Sullivan Street
P.O. Box 910
Wurtsboro, New York 12790
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