Amyloidosis & Swollen Hock Syndrome & Shar Pei Fever

Your questions answered
DR L TINTLE DVM

What is amyloidosis?
A broad term for a collection of diseases that result in the abnormal deposition of amyloids 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 excitable form and instead turn it into Amyloid AA and dump it outside the cells, but still in 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 alleyway until it starts to squeeze the adjacent cell walls.  The compressed cells can’t work properly.  The damaged or disease that results depends on what kind of body cells are most severely damaged or killed.  Kidneys 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.  Less commonly, the liver fails from amyloidosis.

How is amyloidosis diagnosed?
Amyloidosis can only be diagnosed by examining specially stained tissue samples microscopically under polarised light.  Tissues must be obtained by surgical biopsy or, after death, by necropsy.  The veterinarian submitting the sample requests that it be stained with “Congo Red” to detect the presence of amyloid.  Work is being done on a blood test involving monoclonal antibodies of serum amyloid A but this is in the early investigational stages.

How is amyloidosis treated?
Most patients don’t show signs until the 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 he/she refers you to.

How common is amyloidosis in Shar Pei?
The precise incidence of amyloidosis in Shar Pei is impossible to determine at this time.

Does every Shar Pei that dies of kidney failure have amyloidosis?
There are 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.

Most common signs of advanced amyloidosis:

a)       Unexplained weight loss

b)       Increased thirst and frequency of urination

c)       Vomiting

d)       “Bad breath” as a result of uremia or the build-up of
         toxins/wastes in the bloodstream as the kidney and/or
         liver fails to process them

Amyloidosis … a killer
Deaths from amyloidosis have been reported as young as eight months and as old as 12 years.  Most die between 3 and 5 years of age.    Not every dog with FSF will die of amyloidosis but they should be monitored closely by their owners and veterinarians.

What is familial Shar Pei fever (FSF)?
The dog has one or more bouts of unexplained fever, usually 39.5 – 41.6 degrees (C), but rare cases may go higher.  Fevers usually start when the Shar Pei is 18 months old, but sometimes the 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.

How is FSF diagnosed?
There is 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.

Fever episodes may be accompanied by one or more of the following signs:

a)       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).

b)       Sometimes a swollen, painful muscle.


c)       Abdominal pain, reluctance to move, “roached” back,
         mild vomiting or diarrhea, shallow, rapid breathing.

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: recognises “self” from “non-self” and eliminates foreign invaders such as bacteria and viruses and removes cancer cells.  It does this with specialised cells and/or their chemical products.  It is miraculously complex, but is controlled in part by a vast communication 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 controlling 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 …

a)       Excessively high level of certain protective antibodies
         (immunogiobulins)

a)      An exaggerated rate of division of their lymphocytes –
         one of the immune system cells responsible for fighting
         infection and mounting an antibody response –
         when grown in the laboratory and compared to normal dogs.

How is FSF treated?
Fever episodes are treated with anti-inflammatory medication. Extremely high fevers may require more aggressive treatment, similar to that of “heat stroke”.

Colchicine
Experimental … use of this drug needs to be reviewed and treated cases compared to untreated cases before it can be widely accepted. Preliminary results in Shar Pei with FSF are encouraging.

Glomerulonephritis
Shar Pei with FSF may also develop membranous glomerulonephritis with or without amyloidosis as a result of immune complex deposition. Glomerulonephritis is common in immune-mediated diseases. Glomerulonephritis 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.

Therefore …
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.

Opinion on inheritance
Based on extensive pedigree analysis going back to originally imported foundation stock (in the USA).  It is my opinion that 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.

Heterozygous carriers may:

a)         Experience the effects of abnormal immune system             regulation including episodic fevers with or without
            Swollen Hock Syndrome.

b)         May never experience a fever and be asymptomatic,
            silent carriers.

c)          Have an increased risk for thromboembolic disease
            (“strokes” and abnormal blood clots causing disease
            or very rarely, sudden death).

d)          Possibly have an increased risk for an early death
             from certain cancers.

e)          Live out relatively normal lifespans (eight years)
             without ever developing amyloidosis.

Dr Tintle’s recommendation to breeders
“It is my own personal opinion that Shar Pei that have FSF should not be bred.  They carry the gene for this disorder and will pass it on to at least half of their offspring.  If they are bred to another carrier or affected animal (one that will develop amyloidosis) anywhere from 25 – 50% of their offspring will develop amyloidosis.

I cannot recommend perpetuating the heartbreak that this entails.  My studies of pedigrees of dogs with FSF and amyloidosis lead me to believe that in order for the animal to develop amyloidosis, both parents must at least be carriers of the recessive gene.  Therefore, if a dog has any offspring with amyloidosis, I would consider that animal to be at least a carrier whether they have exhibited fevers or not.

For this reason I recommend that all Shar Pei that suffer premature death have tissues checked with Congo Red for amyloidosis and if found, the owners of the sire and dam be notified non judgmentally.  I believe that if a dog is affected with amylodisos, all of its offspring are at least carriers.  If (this affected dog is) bred to another carrier, 50% (of the offspring) will be affected and if bred to another affected animal almost 100% of the offspring will be affected.  PLEASE NOTE:  Breeding two asymptomatic carriers can result in:  25% affected offspring;  50% carriers and 25% normals”.

Article courtesy of Dr L Tintle DVM
Shar Pei Club of Gauteng