I really wanted to do a write up on Shar Pei Fever. This is going to be long, maybe at times boring, but very informative. I know when Chloe first had symptoms of Shar Pei Fever - I went nuts. I DIDN'T know what to do, and I was panicked.
Luckily she has never had to go to the vet for her fevers, but we've been VERY close.
I will post all the links to informative sites right now, then talk.
This is Jeff Vidt's section on Shar Pei Fever - he is a Shar Pei medical specialist
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.
Linda Tintle's write up on FSF and Amyloidosis
An Article by Linda Tintle, DVM
Published in the July/August 1993 issue of The Barker
What is Amyloidosis?
A generic term for a collection of diseases that result in the abnormal deposition of amyloid protein throughout the body.
How is Amyloid Made?
When inflammation occurs, certain chemicals are produced and released into the blood. These chemicals of inflammation are called the Acute Phase Reactant Proteins (APP). After the inflammation has gone away, the APP are broken down by the body and excreted. Dogs (or people) with amyloidosis can't break these APP down into excretable form and instead turn it into Amyloid AA and dump it outside the cells but still within the body.
Why does the Amyloid make them sick?
Amyloid is constantly deposited outside the cells. It builds up like a garbage heap in an alley vay until it starts to squeeze the adjacent cell walls.
The compressed cells can't work properly. The damage or disease that results depends on what kinds of body cells are most severely damaged or killed.
Kidncys can't heal themselves by growing new kidney cells. If a kidney cell dies, it is gone for good and can't be replaced. This is why the amyloid protein usually causes kidney failure first.
tress commonly, the liver fails from amyloidosis.
What is FamiLiial Shar-Pei Fever (FSF)?
l Gave one or more bouts of unexplained fever, usually 103-107 degrees but rare cases may go h igher.
Fevers usually start when they are 18 months old but sometimes first attack is not until they are full grown. Fever episodes usually become less frequent with age.
Fevers last 24-36 hours in most cases without treatment.
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 ("synovitis"). One or more joints may be affected but most cases involve the tibiotarsal or "hock" joint... Swollen Hock Syndrome (SHS).
Sometimes a swollen, painful muzzle.
Abdominal pain, reluctance to move, "roached" back, mild vomiting or diarrhea, shallow rapid breathing.
Swollen hock syndrome was reported to be experienced by up to 53% of those dogs having fever episodes by owners responding to the 1991 National Specialty survey.
What is Familial Mediterranean Fever and What does FSF have in Common with FMF?
An inherited disorder of humans, reportedly as an autosomally recessive trait.
Recurrent bouts of [ever, usually starting in childllood.
Polyserositis, involving one or more of the following:1.Abdominal pain.2. Chest pain.3. Joint pain, usually involving one of the larger joints.4. Swelling/inflammation of skin about the ankle or top of foot.5. Free from symptoms between attacks.6. May develop amyloidosis. Before colchicine therapy, up to 30% of FMF patients died of amyloidosis.
FMF is accepted to be a disorder of the regulation of the immune system, specific defect unknown.
What Causes the Fevers in FSF?
We don't know exactly.
What we Do Know: Shar-Pei seem to have a problem regulating their immune system. The immune system:
Recognizes "self" from "non-self' and eliminates foreign invaders such as bacteria and removes cancer cells.
It does this with specialized cells and/or their chemical products.
It is miraculaously complex but is controlled in part by a vast communocation system involving chemical messengers called CYTOKINES.
Shar-Pei with FSF have abnormally high levels of a cytokine called Interleukin-6.
Interleukin-6 (IL-6) "turns on" various parts of the immune system. It is involved in contl-ol-ling the fever response and is a trigger, alone or with other cytokines, for the production of the APP... the precursors of Amyloid AA.
Shar-Pei with FSF:
Have excessively high levels of certain protective antibodies (immunoglobulins).
Have an exaggerated rate of division of their Iymphocytes... one of the immune system cells rcspollsilgle for fighting infection and mounting an antibody response...when grown in the laboratory and compared to normal dogs.
Why do some dogs with FSF get Amyloidosis and others don't?
Shar-Pei with FSF have an abnormal inflammatory response... the immune system's accelerator pedal, IL-6, is always being pushed, sometimgs a little, sometimes a lot and this probably varies with individuals.
Extra APP are produced chronically.
Some Shar-Pei can't properly excrete the APP and dump them within the body as amyloid.
In people with FMF, the fever disorder and the abnormal production of amyloid protein are believed to be different parts of the same or linked genes.
Patterns of Inheritance
we have submitted a paper which has been accepted by theJorunal of Heredity offering evidence that this disorder is inherited as an autosomally recessive gene. It will be published in late 1993.
Based on extensive pedigree analysis going back to originally imported foundation stock...
Heterozygous carriers, having one normal gene and one abnormal gene for the disorder, do not develop amyloidosis.
Only when doubled up on the abnormal gene... homozygous...do they deposit amyloid.
Normal X CarrierCarrier X CarrierCarrier X Amyloid-AffectedHeterozygous Carriers May:Experience the effects of abnormal immune system regulation including episodic fevers +/- Swollen Hock Syndrome .
May never experience a fever and be asymptomatic, silent carriers.
Have an increased risk for thromboembolic disease ("strokes" and abnormal blood clots causing disease or very rarely, sudden death).
Possibly have an increased risk for early death from certain cancers.
Live out relatively normal lifespans (eight years) without ever developing amyloidosis.
IL-6 has been shown to be a growth factor for malignant plasma cells (plasmacytomas and myelomas) and because IL-6 "turns on" the development of many cell types, it is not unlikely that it may "turn on" abnormal or malignant cell lines as well. This could explain the un- usual number of cancer cases in patients with FSF. I am looking into a study of this with veterinary cancer specialists.
Less commonly, signs of amyloidosis may precede outbreaks of fever or the patient may never experience or report any fever spisodes. This is called "Phenotype II" in FMF.
Deaths from amyloidosis have been reported to me as young as eight months of age and as old as 12 y ears.
Most die between three and five years of age.
Most Common Signs of Advanced Amyloidosis...
Unexplained Weight loss.
Increased thirst and frequency of urination.
"Bad breath" as a result of uremia or the build-up of toxins/wastes in the bloodstream as the kidney +/or liver fails to process them. How is Amyloidosis Diagnosed?
Amyloidosis can only be diagnosed by examining specially stained tissue samples microscopi-cally ull(ler polarized light.
Tissues must be obtained by surgical biopsy or, after death, by necropsy. The veterinarian sublllittillg the sample requests that it be stained with "Congo Red" to detect the presence of amyloid .
Dr. Quimby and his graduate students are working on a blood test involving monoclorlal antibodies of serum amyloid A but this is in the early investigational stages.
How common is amyloidosis in Shar-Pei?
The precise incidence of amyloidosis in Shar-Pei is impossible to determine at this time. Survey Results 1991 National Specialty...23% w/fever of unknown origin. Even if everyone who did NOT return their survey had NO fevers...we would still have...ll+%. That's still a lot of dogs experienceing fever episodes. Private communication with some of the original breeders and importers of the foundation stock of our dogs has led me to believe that many of them were affected by the immune system dysregulation.
How is FSF Diagnosed?
No single test available.
Still a diagnosis of excluding the other possibilities.
Blood tests and cultures are usually negative/normal except elevated WBC with left shift is not uncommon.
What's All This About an IL-6 Test?
Dr. Ariel Rivas is working at the Diagnostic Laboratory of the New York State College of Veterinary Medicine at Cornell University to develop a blood test to measure IL-6 levels of dogs.
Because Shar-Pei with FSF have elevated levels of IL-6, we are hoping to use this as a screen-ing test for this disorder.
Before this, IL-6 levels could only be measured by growing special cell lines in tissue culture media...an elaborately expensive, time consuming and very complicated method.
Questions About The Test...
How old do they have to be to be tested?
How specific is it for this disorder?
Will it tell me if my dog will die from amyloidosis?
Will it be expensive?
How is FSF Treated?
Fever episodes are treated with anti-inflammatory medications, e.g. Dipyrone.
Extremely high fevers may require more aggressive treatment, similar to that of "heat stroke."
Experimental...use of the drug needs to be reviewed and treated cases compared to untreated cases before it can be widely accepted.
Used in FMF to reduce the severity and frequency of fever outbreaks and to block the development of amyloidosielil art rcsults in Shar-Pei ssrith FSF are encouraging.
How is Amyloidosis Treated?
Most patients don't show signs until disease is well-advanced and they are dying. Treatment is difficult if not impossible in most cases.
Treatment of advanced kidney and liver failure needs to be designed to fit the needs of each individual patient and should be left to your veterinarian or specialist she/he refers you to.
We have used colchicine along with more conventional therapies in somc, less advanced cases. Sorne arc still alive two years post-diagnosis. These are the EXCEPTIONS not the rule. More on Treatment and Diagnosis of Amyloidosis...
Dr. Jeff Vidt wrote an excellent article: "Plan of Action for Amyloidosis" in Nov/Dec 1992 issue of The Barker on signs to watch for and treatment of amyloidosis which covers the subject in depth.
I have a treatment protocol for FSF/amyloidosis that I will send to any veterinarian on request.
Does Every Shar-Pei that Dies of Kidney Failure Have Amyloidosis?
Lots of causes of kidney failure and some are related to FSF and some not.
Amyloidosis does, however, seem to be the OVERWHELMING cause of premature death from kidney failure in Shar-Pei but only histopathologic exam (biopsy or necropsy) will tell you for sure.
Shar-Pei with FSF may also develop membranous glomerulonephritis with or without amyloidosis as a result of immune complex deposition. Glomerulonephritis is common in imune-medicated diseases.
Glomemlonephritis forms as a result of the deposition of immune complexes along the glomerular capillary wall and ultimately results in the destruction of the glomeruli within the kidney, loss of protein in the urine and kidney failure.
Other related kidney disease...
Pyelonephritis (infection of the kidney) may occur commonly in FSF/amyloidosis patients.
They can also throw a clot to their kidneys...an "infarct."
These conditions may cause or contribute to kidney failure and are non-amyloid related kidney disease that may be triggered because of their immune system problems for FSF.
A Shar-Pei may die of kidney failure at an early age and be negative for amyloid.
The dog's kidney failure may OR MAY NOT have been related to FSF and at this time. It is impossible to determine any relationship with certainty.
These animals can only be classed as suspicious, unknown.
Currently available diagnostic tests
I recommend a minimum database of CBC with differential, semen chemistry panel, urinaly-sis and urine protein/creatinine ratio for my patients with FSF if the owner is willing. Lyme disease (Borreliosis) should be ruled out in endemic areas.
Immune panels, Immunoglobulin levels, cultures, radiographs and joint taps are sometimes needed .
Can I use urine protein levels to screen my dogs?
Most non-Shar-Pei that develop amyloidosis get a glomerular amyloidosis after nine years of age They spill a lot of protein in their urine.
Humans with FMF and amyloidosis spill a lot of protein in their urine.
Unfortunately, Shar-Pei (and Abyssinian cats with Familial Amyloidosis) most commonly get medullary amyloidosis and they may or may not spill protein in their urine. This makes the test worthwhile (because a positive may be significant and should be followed up with a urine pro-tein/creatinine ratio) but a negative doesn't mean you are safe.
Dr. Linda Tintle, 251 Sullivan Street, P.O. Box 906, Wurtsboro, New York 12790. (914) 888-4884.
Like I said, Chloe has FSF. Her first fever was spring/summer 08. She was almost 6 months old. I freaked. First thing I did was look on Shar Pei Forums for an answer. What do I do!?
Well take her temperatue! So out comes the themometer, (she doesn't like that part) and she had a temperature. Great! Now what? Well get an aspirin to help her with her fever. Aspirin given. Poor girl looked SO miserable. She wouldn't get up, she was shaking, and eventually when she did get up to go outside she wouldn't put any weight on her left leg. Her left hock was super swollen, and very warm. So to help with her fever I wet wash cloths and layed them on her to comfort her. Every so often I would get a syringe and give her water to drink. I also took her temperature ever 20 - 30 minutes. It is said that if the temperature goes above 106 degrees then it is time to go to the vet. Chloe's been to 106.2 before and I was JUST about ready to rush her to the vet, but it went down - thank goodness!
Chloe's fevers usually last before a few hours to three days. Shortest was a few hours, longest was three days (boy was that ever fun!)
After the first fever we (myself, and the breeder) weren't sure if it was FSF. So I didn't put her on Colchicine. After the second fever I put her right on Colchicine, and bought metacam. Metacam is to be given as soon as I spot a symptom of FSF. I find after using Colchicine she hasn't had a severe fever yet. All minor.
Pickles has yet to show any signs...I am hoping he is FSF free.
Chloe's triggers are usually stress and high excitment.
One time she got a fever after seeing a bunny rabbit and getting too excited.
Sometimes it is random as well.
It takes some getting used to, seeing her so miserable, shaking, hot, and uncomfortable. My heart breaks everytime I see her that way.