|
FAMILIAL SHAR-PEI FEVER AND
FAMILIAL AMYLOIDOSIS
OF CHINESE SHAR-PEI DOGS
Linda J. M. Tintle, DVM
(Reprinted from
March/April 1997 BARKER)
SHAR-PEI WITH
FSF:
- Have one or more bouts of unexplained fever, usually
103-107 degrees F (39.4-41.7 C) but rare cases may go higher.
- If they don't have a fever it is not FSF
- 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.
- Fever episodes may be accompanied by one or more of
the following signs:
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:
An autosomally recessive inherited disorder of
humans. 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 ankle or top of foot. Free from symptoms between attacks. May develop amyloidosis.
SHAR-PEI WITH FSF HAVE
ABNORMALLY HIGH 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
cytokine, for the production of the acute phase reactant proteins (APP) or
inflammation ... the precursors of Amyloid AA. Chronically elevated levels of IL-6
leads 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 can not be broken down normally by the animal because of a defect 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 disease. Amyloid compresses the
adjacent cell walls causing cell damage or death. Amyloid is deposited throughout the
body and 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.
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, C van Tassel & F.W. 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. Private communication with many of the original
breeders and importers of these dogs has led me to believe that many of them were
affected by this immune system dys-regulation. 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 episodes. This unfortunately occurs in Shar-Pei as well. Generally,
FSF episodes should be considered to be an important marker that the dog is extremely
high risk to develop amyloidosis and should be carefully monitored.
AMYLOIDOSIS - KIDNEY FAILURE
OR, LESS COMMONLY, LIVER DISEASE/FAILURE. AMYLOIDOSIS IS A KILLER.
- Deaths have been reported to me as young as eight
months of age and as old as twelve years of age. It most commonly strikes between
three and five years of age.
- Amyloidosis can only be diagnosed by surgical biopsy
or 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.
HOW IS FSF DIAGNOSED?
- No single test yet available.
- Still a diagnosis of excluding the other
possibilities.
- Blood test are usually negative/normal except that an
elevated white blood count with a left shift in not uncommon as is a mildly
elevated alkaline phosphatase level.
I PERFORM THE FOLLOWING
MINIMUM DATABASE ON PATIENTS WITH POSSIBLE FSF:
- Complete blood count(CBC) with differential, serum
chemistry panel, complete urinalysis (UA). 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 weeksold 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 Shar-Pei have medullary amyloid may or may not have proteinuria
(unlike humans) but proteinuria is always a significant finding. Loss of ability to
concentrate urine (specific gravity consistently 1.01 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. Research is currently being conducted at the University of Missouri
by Dr. Gary Johnson and staff to attempt to identify the genetic defect associated
with FSF/Amyloidosis in Chinese Shar-Pei.
- This research is being supported by contributions tot
he CSPCA Charitable Trust, c/o Lee Arnold, Chairman, P.O. Box 7007, Bedminster, NJ
07921 U.S.A.
- The gene for FMF was located on human chromosome 16
and efforts are centering on finding a similar defect in the equivalent are of the
canine genome.
- A DNA test should accurately differentiate between
normal, affected and carrier animals whether have experienced fever episodes or not.
We desperately need this test!
TREATMENT OF FSF EPISODES
- Tender loving care, close observation of body
temperature and otherwise benign neglect.
- Buffered aspirin.
- 50% Dipyrone, Banamine (flunixin meglumine) to reduce
fever and provide pain relief.
- Extremely high fevers or other evidence of severe
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. 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 myself. 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. We would appreciate hearing about
any new cases.
COLCHICINE
- Used in humans for over 400 years and most commonly
used as the 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
prophlactictically in any Shar-Pei which I believe to have FSF as soon as I am
convinced that this is what the dog has. I do not recommend waiting until evidence of
disease due to amyloidosis is seen. At that point, it is almost too late.
- We have some Shar-Pei on Colchicine for over four
years and I have yet to see evidence
- of 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 three years of age, in pregnant women and when given
lifelong. Fatalities associated with massive overdose 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 for two weeks and if
no gastrointestinal problems have occurred, I double the dose to 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. So far, no research has been
conducted/funded to do so but I have kept careful records and Dr. DiBartola at Ohio
State University who did the original studies on amyloidosis in Shar-Pei has
expressed an interest in overseeing such a study.
- 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 the 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 FEVER EPISODES AND THE DEVELOPMENT OR DEGREE OF
AMYLOIDOSIS
A dog that experiences on single fever episode in
his entire life is just as likely to get amyloidosis as the dog that gets them every
seven to ten days. They should be considered a marker for high risk for the disease.
This is also why I do not recommend waiting to see if they ever get another one!
MOST COMMON SIGNS OF ADVANCED
AMYLOIDOSIS
- Unexpected 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 ... Omega three fatty acids, low dose
aspirin therapy, enalapril, superoxide dimutase and other free radical scavengers may
be indicated in some individual cases.
- Thromboembolism "throwing a clot" is not
uncommon in these patients and is why low dose (1/4 a baby aspirin once daily)
may be recommended.
- Liver disease often shows up as severe jaundice along
with weight loss, vomiting and inappetence. 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 four 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.
251 Sullivan Street
P.O. Box 910
Wurtsboro, New York 12790
For more information about
amyloidosis and how you can help, please visit the CSPCA's website and learn more about
the:
CSPCA Charitable Trust
[BACK]
|