Shar-Pei Fever and Familial Amyloidosis of Chinese Shar-Pei Dogs
J.M. Tintle, D.V.M.
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
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.
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
Characterized by recurrent bouts of fever, usually starting in
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
Swelling/inflammation of the skin about the ankles or top of the
Free from symptoms between attacks.
May develop amyloidosis.
with FSF have abnormally high resting levels of a cytokine called
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.
is an autoinflammatory disease characterized by dysregulation
of the normal paths of inflammation.
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.
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
kidney failure or, less commonly, liver disease/ failure.
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.
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.
is FSF diagnosed?
No single test is yet available
Still a clinical diagnosis by history, signs and excluding the
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.
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.
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
of FSF episodes.
Tender loving care, close observation of body temperature and
otherwise benign neglect.
Buffered aspirin, Metacam (metacarpfen) - Canadian S-P owners
have reported that this has worked very well in reducing fever
and I am starting to recommend having it on hand to my clients'
whose dogs experience episodes of fever now that it is available
in the U.S.
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.
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 (although other bacteria
have been cultured as well) and require aggressive antibiotic
and supportive treatment. These can be fatal even with treatment.
A recent reports suggest that this is an immune mediated vasculitis
and steroids +/- azathioprine may be indicated.
Acute febrile neutrophilic vasculitis of the skin of young Shar-Pei
Aust Vet J 80:200-6 2002 Apr
vasculitis in a shar-pei with swollen hock syndrome.
Can Vet J 42:137-9 2001 Feb
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. Here is a photo of a very severe
case that did survive despite lesions covering large portions
of her body:
is a very, very rare complication of an FSF episode.
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
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
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.
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!
Common Signs of Advanced Amyloidosis.
Unexplained weight loss.
Increased thirst and frequency of urination.
"Bad Breath" as a result of uremia (the buildup of toxins/wastes
in the bloodstream as the kidney +/- liver fails to process them).
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
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.
causes of kidney failure in Shar-Pei
(or... Why you need to get
the biopsy/necropsy specimens).
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.
J.M. Tintle, D.V.M.
Wurtsboro Veterinary Clinic, P.C.
163 Sullivan Street
P.O. Box 910
Wurtsboro, New York 12790