Breed Problems in the Shar-Pei, by Jeff Vidt, DVM

There is no perfect dog breed…every breed has its problems and imperfections. The easiest way to discuss the problems seen in our breed is to list them according to the body system involved. Please remember that these problems are seen in a very small number of dogs…not every Shar-Pei will be affected:

1. RESPIRATORY
  • stenotic (pinched) nostrils
  • elongated soft palate
  • pneumonia — primarily in puppies
2. EYES
  • entropion — rolling in of the eyelids
  • retinal dysplasia
  • glaucoma
  • “cherry eye” — prolapse of the gland of the third eyelid
  • lens luxation
  • cataracts
3. EARS
  • stenotic (narrow) ear canals
  • bacterial ear infections
  • yeast overgrowth
  • hyperplastic otitis
4. GASTROINTESTINAL
  • bite problems — most commonly, an overbite
  • inflammatory bowel disease
  • megaesophagus
  • hiatal hernia
  • intestinal adenocarcinoma
  • bloat (gastric dilatation/volvulus)
5. SKIN
  • lip fold pyoderma
  • skin fold pyoderma
  • demodectic mange
  • allergic skin disease — allergic inhalant dermatitis, food allergy,
    insect allergy, contact allergy, etc.
  • generalized pyoderma
  • cutaneous mucinosis
6. ENDOCRINE
  • hypothyroidism
  • hypoparathyroidism
7. MUSCULOSKELETAL
  • inquinal hernias
  • luxating patellas — “loose” kneecaps
  • elbow dysplasia- hip dysplasia
  • anterior cruciate ligament rupture
8. GENITOURINARY
  • renal amyloidosis
  • immune-mediated kidney disease
9. NEOPLASIA
  • mast cell tumor
  • histiocytoma
  • lymphosarcoma
  • intestinal adenocarcinoma
  • hemangiosarcoma
  • systemic melanosis
  • systemic histiocytosis
10. MISCELLANEOUS
  • Familial Shar-Pei Fever (FSF)
  • abscesses — bite wounds, other
  • IgA deficiency
  • Primary Multiple Immunodeficiency Syndrome of Shar-Pei
  • amyloidosis

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News From Dr. Vidt Concerning Colchicine Availability

URL Pharma was recently purchased by Takeda Pharmaceuticals, USA (2012). Takeda has chosen to continue the Patient Assistance Program (PAP) extended to the Chinese Shar-Pei owners for Colcrys® (colchicine). The new application form is on my web site Home Page (www.drjwv.com) and should be used from now on.

Applicants must provide a valid Colcrys® prescription from a licensed veterinarian and must attest that Colcrys® will be used only for their Shar-Pei dog. Applicants who qualify for the program will be able to select a 30-day supply (60 tablets), a 60-day supply (120 tablets) or a 90-day supply (180 tablets) of Colcrys®. It is important to note that Colcrys® is not FDA-approved for veterinary use and URL Pharma does not promote the use of Colcrys® in animals. The application is attached to this update in a .pdf format.

* Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com and www.drjwv.com Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

Discount App for Colchicine

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Amyloidosis By Jeff Vidt, DVM

Amyloidosis is the deposition of an abnormal substance called amyloid in the tissues of the body. Amyloidosis is not a disease as much as it is a specific biochemical arrangement in which a precursor protein or protein fragment accumulates and forms filaments. These filaments align and stack themselves in a beta-sheet conformation forming fibrils that twist around each other and are deposited in the tissues as amyloid deposits. Amyloid deposits differ due to the nature of the protein precursors that form there. Due to this structure amyloid is insoluble and can be thought of as “wax”. There are currently at least 11 different protein precursors in amyloidosis. Many of these have specific tissues they accumulate in and have specific clinical signs or syndromes associated with them. As an example in humans Alzheimer’s patients have amyloid deposition in the brain due to an unknown precursor protein. In animals the only form of amyloidosis shown to occur at this time is reactive amyloidosis. Here the precursor protein is serum amyloid A protein and amyloid A composes the fibrils in the amyloid deposits. All amyloid deposits stain with Congo Red and have a characteristic green color with birefringence under polarized light. Of the many types of amyloidosis which stain with Congo Red only reactive amyloid and beta-2 microglobulin amyloid are decolorized by potassium permanganate oxidation. Beta-2 microglobulin amyloid has only been described in humans on long-term hemodialysis for chronic renal failure and has not been found in animals. The amyloid in Shar-Pei is definitively reactive amyloidosis. It is also important to realize that amyloidosis is not a single disease, but can be the end point of many diseases.

This form of systemic amyloidosis, reactive amyloidosis, usually occurs with chronic inflammatory diseases and is characterized by the presence of amyloid protein AA. Amyloid protein AA is derived from an acute phase protein called serum amyloid A protein (SAA) produced by the liver. There are many other acute phase proteins produced by the liver which have important roles in the inflammatory process and in tissue repair after injury. It is important to understand that amyloid protein AA is a normal protein and that it’s production is a normal response to tissue injury and inflammation. It is also important to realize that many diseases, traumatic injuries, cancer disorders, stresses, etc. can stimulate the production of the acute phase proteins. There appears to be a balance between the production of SAA and the degradation and excretion of SAA from the body. It is not known whether the development of amyloidosis in the Shar-Pei is due to prolonged excessive SAA production by the liver which overwhelms the degradation mechanisms or a defect in the degradation process itself, or a combination of both. We do know that Familial Shar-Pei Fever is an inflammatory process which does stimulate the synthesis and release of acute phase proteins from the liver. That this occurs can be surmised from the changes seen on the hemogram and biochemical profiles of Shar-Pei during, or shortly after, an FSF episode. It certainly appears that the cause of amyloidosis in Shar-Pei has a genetic basis.

Reactive amyloidosis results in extracellular deposition of amyloid protein in tissues. This means the “waxy” amyloid is surrounding the cells and slowly crushes them as well as interfering with nutrition of the cells. These cells die and the structures they make up are replaced by fibrous, nonfunctional scar tissue. There are species differences as to which tissues amyloid will accumulate in. In dogs, the kidney is the primary organ involved with the spleen and liver affected less often. The kidney is especially vulnerable due to its decreased ability to replace damaged cells and ultimately, when a certain number of cells have been irreparably damaged, kidney failure with its accompanying clinical signs develops. Once amyloid is deposited in the tissues it appears that nothing can remove it although recently a new class of drugs have been discovered which may do just that.

It is important to realize that amyloidosis occurs in all dog breeds and in a number of inflammatory and immune-mediated conditions. The majority of amyloidosis in dogs is idiopathic or of unknown cause. Amyloidosis can occur secondary to heartworm disease, tick-borne diseases, various cancers, systemic lupus, immune-mediated arthritis, IBD, etc. I suspect that the tendency to develop amyloidosis in response to inflammatory or immune-mediated disease or triggers is a separate genetic disease in dogs which leads to failure to degrade amyloid, failure to excrete amyloid degradation products or increased production of amyloid precursors.

Why does amyloidosis have so many different clinical presentations? Why does it occur in some Shar-Pei at 2 years of age and in others at 10 years of age? Why do some Shar-Pei develop amyloidosis and others don’t? Why is it a genetic disease in Shar-Pei? There are many questions which have no answers at this time. I think several theories are plausible to explain the variations we see:

The underlying trigger of amyloidosis in Shar-Pei is Familial Shar-Pei Fever (FSF). It is quite possible that FSF has variable age of onset and variable degrees of severity in terms of the inflammatory disease it causes. This may result in a variable rate of progression in the development of amyloidosis in different individuals. For example, the response of the liver to FSF and the synthesis and release of the acute phase proteins, especially SAA, may be more acute in some dogs resulting in a more rapid deposition of amyloid. In other individuals, the response to FSF may be more chromic and result in slower deposition of amyloid. In effect, there may be milder forms and more severe forms of the same disease. The exact mechanism of amyloid deposition may be different in different individuals. There may be other effects of FSF on the body which are additive with the amyloidosis. As an example, we know Shar-Pei are more susceptible to disseminated intravascular coagulation (internal blood clotting) during an episode of FSF and blood clots in the kidneys may cause more kidney damage than just amyloid deposition itself. Some dogs may have other disease processes going on which can be additive with the effects of amyloidosis.

These are just some ideas on why we see different presentations of the same disease. One fact remains – any amyloid deposits found in a Shar-Pei have to be regarded as related to FSF and genetic until proven otherwise. It really doesn’t matter whether a little or a large amount of amyloid is found. Another point to keep in mind is that the mechanisms initiating amyloid deposition are normal protective responses seen in any breed of dog. It appears in our breed that the mechanisms, which regulate the inflammatory response, don’t work properly allowing this normal response to go out of control and cause disease.

Relationship of FSF and Amyloidosis

There is a definite relationship between FSF and amyloidosis. FSF is undoubtedly a genetic condition which is inherited much as the periodic fever episodes seen in humans. FSF is a built-in trigger resulting in intense inflammation and the release of acute phase proteins from the liver one of which is serum amyloid A. I think there are several explanations for the wide variety of clinical presentations we see with FSF/amyloidosis. I suspect that there are several different mutations which can result in FSF. We know in humans with Familial Mediterranean Fever that there are at least 8 mutations in the FMF gene leading to differences in severity of clinical signs, duration, illness and death in different populations. I think we see the same thing in Shar-Pei, some having mild episodes and some having very severe episodes. This may also explain why some dogs succumb to STSS, DIC, heat stress, and other complications but others don’t. That being said I also suspect that there are variations in the genetic defect predisposing to amyloidosis in dogs in general. One can imagine in a dog with a severe form of FSF resulting in dramatic increases in serum amyloid A and having a genetic defect leading to a decrease in degradation of amyloid that the rate of amyloid deposition would be very high. On the other hand if the type of FSF resulted in mild increases in serum amyloid A in a dog with no amyloid defect then amyloidosis would not develop. The same seems to hold true with the dog population in general since not all dogs with inflammatory/immune-mediated diseases develop amyloidosis and some dogs with amyloidosis have no discernable underlying disease to blame for it.

I think it is safe to say that FSF is not the only precursor to the development of amyloidosis in the Shar-Pei but certainly is the major factor since FSF is only seen in our breed. Is it possible that FSF is revealing those animals with an amyloidosis defect of some kind? The high fever seen in FSF certainly results in increased levels of serum amyloid A thus facilitating the development of amyloidosis. Thus it appears FSF and amyloidosis most often occur together in Shar-Pei but can occur separately as well. Since idiopathic amyloidosis occurs in dogs in general (the most common cause of amyloidosis in other breeds) we can expect it would occur in the Shar-Pei also so not all cases of amyloidosis in our breed are related to FSF.


H & E Stain: The pink-staining material in the collecting ducts, tubules and glomeruli is amyloid. Unfortunately protein in the tubules will also appear the same. Only Congo Red staining can differentiate amyloid deposits.

Congo Red Stain: The areas of birefringence are due to amyloid.

Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com andwww.drjwv.com Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

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Plan of Action for Amyloidosis By Jeff Vidt, DVM

This article by Dr. Vidt presents a plan to monitor Shar-Pei with the goal of uncovering renal amyloidosis as early as possible and then instituting appropriate dietary and medical intervention. It does contain some technical terms which your veterinarian may be able to simplify for you. The author urges you to discuss this article with veterinarian and then both of you can work together in dealing with this troubling disease.

Renal amyloidosis has hit the Shar-Pei fancy in recent years and left many of us feeling helpless as we watch young Shar-Pei sicken and die before our very eyes. We don’t have to sit and take it, but can gather the facts and formulate a plan of action. What I propose in this paper is based on the information available today about renal amyloidosis. Currently, there is no test available to help pinpoint Shar-Pei at risk for developing the condition and due to ethical considerations, information concerning pedigree analysis is not available to help determine those dogs who have the condition in their background. What we are left with is to try to uncover the condition in our dogs as early as possible and to institute steps to minimize the effects on our dogs and increase longevity. The following plan has no guarantees and certainly will change as new information becomes available, but it represents a starting point and a step to build on further.

Keeping a Watchful Eye for the Health of your Shar-Pei

As a Shar-Pei owner you can do the following simple steps:

  1. Monitor weight – This involves weighing your dog at regular intervals using a scale. Do not rely on eyeball judgements. Too often I see dogs in an advanced state of weight loss which the owner has just noticed, but which has been going on for several weeks. Remember, we are trying to uncover this condition at its earliest point – minor weight loss can indicate early renal amyloidosis.
  2. Monitor appetite – Daily fluctuations in appetite do occur, but a change in what is normal for your dog may indicate early kidney problems.
  3. Monitor water consumption – A normal dog consumes approximately 1 oz. of water per pound of body weight per day. This varies with activity level, season of the year, type of food being fed (canned vs. dry), etc. I advise measuring water intake periodically by measuring how much water is put down in the morning and measuring it again at night. Obviously this will involve a little more ingenuity on the owner’s part when multiple dogs are involved. Increased water consumption may indicate early kidney failure.

In addition to the above home monitoring program, I also advise having your veterinarian check a urine sample every three months on any Shar-Pei over two years of age. The main parameters I watch in the urine are the urine specific gravity and the urine protein reading. Urine specific gravity is a measure of the concentration of the urine. If the kidneys were not functioning at all this reading would be 1.008 – 1.012 (a dilute urine). Normal concentration should be above 1.025 and sually is greater that 1.045 (a concentrated urine). Ideally the urine sample should be a morning sample collected after the dog’s water bowl has been removed overnight (remember to close the toilet lid!). By depriving the dog of water overnight we force the kidneys to concentrate the urine, if they are able to do so. Inability to concentrate urine indicates that approximately 75% of the kidneys are non-functional – this is still compatible with life, but treatment needs to be started quickly to preserve the remaining kidney function.

The other urine test I heavily rely on is the urine protein level. The stick test routinely run by veterinarians primarily measures urine albumin levels. An elevated urine albumin level means that protein is being lost in the urine and correlates with glomerular damage (the glomerulus is the filtration unit of the kidney and serves to filter out the waste products of the body). High levels of protein in the urine indicates significant kidney disease and additional testing needs to be done to obtain a diagnosis. A new more quantitative microalbuminuria test is now available for in-hospital use from Heska, the E.R.D.-Screen™ Urine Test. The “gold standard” for proteinuria is the urine protein/creatinine ratio (UPC) which is run by all the commercial veterinary laboratories.

It appears that there are three separate syndromes associated with renal amyloidosis in the Shar-Pei:

  1. Glomerular – If the amyloid deposits occur primarily in the glomerulus, we see increased protein levels in the urine.
  2. Tubular – If the amyloid deposits occur in the tubular part of the kidney we see loss of concentrating ability which manifests as a dilute urine.
  3. Combination – This occurs when amyloid is deposited in both the glomeruli and the kidney tubules and we see increased protein levels in the urine and dilute urine.

The clinical signs and the routine urine check constitute the first level of diagnostics. If the urine sample is abnormal and one or more clinical signs are present, then we immediately proceed to the second level of diagnostics. This level incorporates the following tests:

  1. A complete blood count – This includes a packed cell volume, a white blood cell count, red blood cell count, platelet count, and a white blood cell differential count.
  2. A health panel – This includes at least a BUN, creatinine, sodium, potassium, calcium, phosphorous, cholesterol, total protein, albumin, globulin and, glucose. It often includes liver tests and thyroid hormone levels.
  3. An immune panel – This should consist of a direct Coomb’s test, an anti-nuclear antibody test (ANA), a Rheumatoid arthritis factor test (RA), and an LE prep for systemic lupus.
  4. A urine protein/creatinine ratio – A value above 1.0 is considered abnormal and indicates excessive urine protein loss.
  5. Abdominal radiographs – Used to evaluate kidney size and shape.

Based on the results of the first and second level diagnostics the following steps are taken to manage the patient:

  1. Diet – A low protein diet is initiated using Hill’s Prescription Diet K/Dâ or its home-made counterpart. I’m also using the Iams Eukanuba Veterinary Kidney Diets – Early Stagesâ and Advanced Stagesâ. There are other kidney diets available as well by other pet food manufacturers.
  2. Vitamin-mineral supplementation.
  3. Ascriptinâ – 1/4 tablet once a day or low dose aspirin(81mg) ½-1 tablet daily.
  4. 1-2 cooked eggs per day – used in cases where albumin is being lost in the urine.
  5. Additional medical therapy may be instituted using either colchicines tablets or DMSO via injection or orally. The effectiveness of both these drugs in the prevention and treatment of renal amyloidosis in the dog has yet to be substantiated, but their use is justified given the grave prognosis of this condition in the Shar-Pei. Colchicine is a human anti-gout medication whose mode of action is largely unknown. It appears to prevent the formation of amyloid in the laboratory, but whether this occurs in the living animal is not known. Dimethyl sulfoxide (DMSO) is another drug whose mode of action is unknown, but has demonstrated the property of dissolving amyloid in the laboratory. Again, whether this action occurs in the living animal is unknown. The dosages are as follows:
    1. Colchicine – this dose can be obtained from Dr. Linda Tintle or myself (see the July/August 1992 issue of The Barker).
    2. DMSO – numerous dosages are in the veterinary literature. Your veterinarian should refer to an excellent article on renal amyloidosis by Dr. DiBartola in Current Veterinary Therapy XI.

      [IMPORTANT! – DMSO imparts an odor to the breath and skin of the patient.]

      Again, the effectiveness of these drugs in the treatment of amyloidosis has not been proven in clinical studies and hence, they should be regarded as experimental drugs for this use. They should be used only under the supervision of your veterinarian.
  6. Equally important is the avoidance of further kidney damage.
    1. Avoid dehydration- provide plenty of fresh water daily.
    2. Avoid kidney-damaging drugs such as aminoglycoside antibiotics, methoxyflurane anesthesia, various chemotherapeutic agents, sulfonamide antibiotics, etc.
    3. Avoid stress- boarding, traveling, showing, etc.

Third level diagnostics may be done depending on your veterinarian or the availability of specialists in your area. Test at the level may include:

  1. Coagulation panel – Increased levels of fibrinogen may indicate impending thromboembolism (throwing of blood clots) associated with DIC (Disseminated Intravascular Coagulation) especially if associated with increased cholesterol and decreased albumin levels (nephrotic syndrome). This panel should include a platelet count and a measurement of FDP’s (Fibrin Degradation Products).
  2. Fractional clearances of various eletrolytes (sodium, potassium, calcium and phosphorous).
  3. 24-hour urine protein excretion.
  4. Creatinine clearance testing to evaluate kidney function (glomerular filtration rate – GFR).
  5. Kidney ultrasound.
  6. Kidney biopsy.

The kidney biopsy is the definitive diagnosis of renal amyloidosis and the decision to biopsy should be made early in the course of the disease for a number of reasons:

  1. Early on, the animal is a much better surgical candidate and many complications of renal amyloidosis such as bleeding tendencies and uremia are not present.
  2. There is a real danger in the Shar-Pei to blame every kidney problem on renal amyloidosis and fail to pursue other causes of kidney disease such as kidney infection, heartworm disease, and immune-mediated diseases like systemic lupus and immune-mediated glomerulonephritis.
  3. The information from an early kidney biopsy can guide the medical and dietary management of the case and provide valuable prognostic information.

Almost as important as the early diagnosis of renal amyloidosis is the continued monitoring of the patient while on therapy. This allows us not only to monitor and watch for the progression of the disease, but also to evaluate the various therapeutic modalities and determine which are effective and which are not. Monitoring at one to two week intervals initially and then at monthly intervals thereafter is recommended. I usually repeat a kidney panel and cholesterol level, a CBC, and a urinalysis including a urine protein/creatinine ratio.

Continued monitoring is also important in order to pick up the early signs of sequelae to renal amyloidosis such as:

  1. Nephrotic syndrome – characterized by decreased serum albumin, increased serum cholesterol and increased protein loss in the urine. A serious complication of this syndrome is thromboembolism (“throwing blood clots”). Your veterinarian may do a blood fibrinogen level and coagulation panel to evaluate the blood clotting system. If the fibrinogen level is >300 mg/dl, aspirin therapy is strongly indicated. Another serious complication of this condition is the development of edema or fluid accumulation in the abdomen or chest and in the limbs. In this case, the use of diuretics such as Lasix may be necessary.
  2. Uremia – or the accumulation of body waste products which are normally filtered by the kidneys into the urine. The build-up of these wastes causes clinical signs such as appetite loss, weight loss, vomiting, diarrhea, depression and lethargy. More serious effects include anemia (decreased red blood cell production) and gastrointestinal ulceration. Treatment here may include intravenous fluid therapy, dietary therapy such as Hill’s Science Diet U/Dâ, Iams Eukanuba Veterinary Kidney Diet – Advanced Stagesâ, phosphate binders such as Amphojelâ, ulcer medication such as Carafateâ and other therapy as deemed necessaryby your veterinarian. Eventually, uremia will progress and lead to the death of the animal. As an aside, current nutritional research indicates that there is no advantage to instituting dietary protein restriction prior to the onset of kidney failure. This means that feeding protein-restricted diets prior to developing laboratory or clinical signs of kidney failure will not prevent kidney failure.
  3. Hypertension – The kidneys are very important in the regulation of blood pressure. It is speculated that up to 80% of the dogs in kidney failure have significant hypertension as a consequence. The use of indirect blood pressure monitoring in animals has recently become available to the veterinarian and hopefully will lead to more advances in this area. Your veterinarian may wish to institute therapy using vasodilators and/ or diuretic medication.
  4. Disseminated Intravascular Coagulation (DIC)– The body’s coagulation system is in a fine state of balance between forming blood clots and dissolving them. When this balance is disrupted coagulation factors are used up before they can be replaced and out of control bleeding is the result. This condition is associated with high mortality and is a poor prognostic factor. Treatment is not very effective.
  5. Streptococcal Toxic Shock Syndrome (STSS) –This is an unusual complication which results in areas of skin death leading to skin sloughing almost like a burn. The condition seems to be caused by toxins produced by Streptococcus canis and is rapidly fatal sometimes in spite of treatment.

It should be mentioned here that DIC and STSS are also complications following episodes of Familial Shar-Pei Fever (FSF). FSF appears to be a potential trigger for the Systemic Inflammatory Response Syndrome (SIRS) which can stimulate the development of DIC and STSS. Ultimately, these end up in the development of Multiple Organ Dysfunction Syndrome (MODS) if early and aggressive treatment is not initiated. The bottom line is that no episode of FSF should be treated lightly. I recommend that my clients call me with each FSF attack and certainly bring the dog in if the episode is not responding to aspirin, is lasting longer than usual, they notice any usual symptoms or the fever is very elevated.

To what extent early diagnosis and monitoring contributes to the longevity and quality of life of renal amyloidosis patients is hard to quantify at this time. My feeling is that it is possible to slow the progression of the condition and improve the short-term prognosis for these patients. We can probably add several months to their life span. It’s expensive and requires diligence and hard work on the part of both the owner and their veterinarian, but the reward is some extra time with a close friend.

Chronic Renal Failure Treatment

Any or all of the following therapeutic agents may be used in the treatment of chronic renal failure in Shar-Pei. The definitive treatment of your dog will depend on decisions made with your veterinarian. Dosages are based on my experience and may be adjusted by your veterinarian based on their experience or on more recent dosage information.

  1. Fluid therapy – in-hospital treatment typically involves intravenous administration. Home care may involve subcutaneous administration. May add B vitamins to stimulate appetite and replace water-soluble B vitamins. Rate is usually 2-3 times maintenance.
  2. Histamine H2-receptor antagonists to inhibit stomach acid secretion. These include Tagamet HB®, Pepcid® and Zantac® tablets.
    1. famotidine (Pepcid AC®) 0.5 mg/kg sid-bid 10 mg tablet
    2. ranitidine (Zantac®) 2mg/kg tid 75,150, 300 mg tablets
    3. nizatidine (Axid®) 5 mg/kg sid 150,300mg capsules
    4. cimetidine (Tagamet HB®) 10mg/kg bid 100, 150, 200, 300 mg tablets
  3. Aspirin 81mg tablets – ½ – 1 tablet once a day for hypercoagulability problems.
  4. Phosphate binders – typically aluminum hydroxide agents such as Basaljel®, Amphojel®, Maalox® and others. Average Shar-Pei would be dosed at 200mg three times a day.
    1. Aluminum hydroxide 30-90 mg/kg/day
    2. Aluminum carbonate 30-90 mg/kg/day
    3. Aluminum oxide 30-90 mg/kg/day
    4. Calcium acetate 60-90 mg/kg/day
    5. Calcium carbonate 90-150 mg/kg/day
    Another agent is sevelamer (Renagel®) dosed at 30-135 mg/kg/day divided given intact with meals. This drug does not promote hypercalcemia or absorption of aluminum. Should monitor clotting ability when used in dogs (PT).

    A new veterinary product is Epakitin® available from Vetoquinol which contains chitosan from shellfish to bind phosphorus. An average Shar-Pei would receive 3 measuring spoons twice a day with food.
  5. Metoclopramide (Reglan®), an anti-emetic at 5-10mg three times a day for vomiting. Zofran® (ondansetron) 0.5-1.0mg/kg 30 minutes before food. Dansetron mesylate (Anzemet®) is an injectable anti-emetic which is given once a day at 0.3mg/kg.
  6. Pet Tabs® (vitamins) 1 tablet twice a day.
  7. 3V Caps® (large breed) 1 capsule once a day – a fatty acid supplement as an anti-inflammatory agent for the kidneys.
    1. omega-3 FAs promote kidney function
    2. 200 – 250 total omega-3 FAs/kg/day
    3. Food = 1-2% total omega-3 FAs
    4. N-6:N-3 ratio = 2:1
  8. Colchicine 0.6 mg twice a day – amyloidosis.
  9. Human recombinant erythropoietin (Epogen®, Procrit®) for nonregenerative anemia (low red blood cell count) associated with chronic renal failure. Start with 100U/kg subcutaneous injection 3 times a week until PCV is between 37-45% then decrease schedule to one injection a week. MUST monitor PCV and serum iron levels. Dogs can develop antibodies to this drug.DO NOT USE IN DOGS WITH HIGH BLOOD PRESSURE! We want to delay the use of human EPO due to the risk of antibody production against the hormone (22%) and the potential of more serious possible cross antibody attack against the patients’ bone marrow – bone marrow aplasia.
  10. Enalapril (Enacard®, Vasotec®) 10 mg tablets ½-1 tablet once a day for protein-losing glomerulopathy. Benazepril (Lotensin®) 1 tablet sid 5mg tablet
  11. Prescription Kidney Diet – generally low protein and low phosphorous. Hill’s K/D or U/D Diet®, Iams Eukanuba Veterinary Diets Nutritional Kidney Formula Early Stages or Advanced Stages Diet®, Purina CNN Kidney Diet®, others. THE MOST IMPORTANT GOAL IS TO KEEP THE PATIENT EATING – THERE IS NO POINT IN STARVING THE PATIENT TO USE THE CORRECT DIET!! Feed smaller meals more often – more likely to hit the dog when they feel like eating.
  12. Appetite stimulants such as cyproheptadine (Periactin®) at 5-20mg one to two times a day and mirtazapine. Propofol at 1mg/kg IV stimulates appetite within 15 minutes. B vitamins via injection or added to subcutaneous fluids may stimulate appetite also.
  13. Proton pump inhibitors — Prilosec® (omeprazole) 20 mg/dog sid (0.7 mg/kg) 20mg capsule.
  14. Ulcer adherent complex — Carafate® (sucralfate) 0.5-1.0gm/dog bid-tid 1 gm tablets.
  15. Sodium bicarbonate 650 mg tablets — 2 tablets tid based on base excess. Try to maintain plasma HCO3 concentration at 15 mEq/l or greater.
  16. Ferrous gluconate 242mg tablet – ½ tablet sid (see discussion under EPO).
  17. A new veterinary product called Azodyl® available from Vetoquinol. It relies on a process called “enteric dialysis” which utilizes bacteria to fix nitrogen in the colon. This reduces uremic toxins. The dose for an average size Shar-Pei is 2 capsules in the AM and 1 capsule in the PM.
  18. Calcitriol – when serum phosphorus concentration ≤ 6 mg/dl. Initial dose is 2.5ng/kg/day. May increase calcitriol doses about 0.75-1.0ng/kg to a maximum dose of 5ng/kg. Treatment endpoint is to normalize serum PTH levels without inducing hypercalcemia.
  19. Amlodipine besylate (Lotensin®) is a calcium channel blocker used in treating hypertension. Start dosing at 0.1mg/kg orally b.i.d. and up-titrate weekly while monitoring blood pressure.
  20. ACE (Angiotensin I Converting Enzyme) AT1 receptor antagonists – irbesartan (Avapro®) 5-30mg/kg once a day, telimsartan(Micardis®) 0.1-1.0mg/kg once a day.

Lastly, when the end does come, consider allowing your veterinarian to do an autopsy on your dog. Especially important is the evaluation of the kidneys through histopathology. We must verify cases of renal amyloidosis or other causes of kidney failure if we are to make headway in correcting this condition through breeding. Results can be sent toDr. Linda Tintle, Wurstboro Veterinary Clinic, PC, 251 Sullivan Street, P.O. Box 906, Wurtsboro, New York, 12790.

I currently maintain a web presence at www.drjwv.com . My hope is to update this site periodically as new information becomes available. This site represents my own opinions based on reading the veterinary literature and in no way reflects the opinions of the CSPCA, Inc. or anyone else.

The Officers and Board of Directors of the Chinese Shar-Pei Club of America supports research for Familial Shar-Pei Fever and amyloidosis. Donations can be sent to the Chinese Shar-Pei Charitable Trust, Lee Arnold, Chairman, P.O. Box 428, Saddle River, NJ 07458

All donations will be acknowledged in future issues of The Barker.

Many of us have felt the pain and loss of a wonderful Chinese Shar-Pei. Let us feel the joy in helping find solutions.

Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com  and www.drjwv.com  Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

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Familial Shar-Pei Fever By Jeff Vidt, DVM

Familial Shar-Pei Fever (FSF) is a hereditary inflammatory disorder seen in Shar-Pei. It appears to be inherited as an autosomal recessive condition.

Clinical signs: Episodic fever is the most important and consistent clinical sign of this disorder. The tempera-ture commonly is in the 104-107°F (40°C-41.7°C) 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 and/or muzzle. 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. There can be gastrointestinal signs such as mild vomiting and diarrhea as well. These signs are related to synovitis of the affected joint(s), pleuritis and/or peritonitis (inflammation of the lining of the thoracic/abdominal cavity) and the accompanying pain. Along with these clinical signs they are also not eating or drinking.

Pathogenesis: What we do know about this disease is as follows:

  1. The major function of the immune system is to recognize “SELF” and “NONSELF” and then react appropriately to eliminate the “NON-SELF” antigens. There are two arms of the immune system – INNATE IMMUNITY and ADAPTIVE (HUMORAL) IMMUNITY. The innate immune system is set up to react quickly by generating an inflammatory response. This is initiated by a group of proteins known as PAMPs or Pathogen-Associated Molecular Pattern proteins. The innate immune system is pre-programmed to a respond to a wide variety of environmental triggers. The adaptive immune system is slower in onset and has the advantage that it “remembers” previous encounters. Hence it “learns” and reacts quicker and stronger in future episodes. Both these legs work together to lessen the impact of bacteria, foreign material, viruses, fungi, tumor cells, etc. on the body.
  2. Inflammation is a normal response in the body and is finely controlled by a “checks and balances” system which regulates the duration and intensity of the response. There are systems in place which turn “ON” the system and turn “OFF” the system to maintain balance.
  3. A genetic defect in the innate immune system can lead to uncontrolled inflammation resulting in AUTOINFLAMMAORY disease – a syndrome of continuous (constant “ON”) inflammation which is not healthy. A genetic defect in the adaptive immune system leads to an over-reactive immune response resulting in AUTOIMMUNE disease (the body reacting to itself).
  4. FSF is classified as an AUTOINFLAMMATORY DISORDER due to a genetic mutation in innate immunity and may be the first such described disorder in dogs. There are a number of autoinflammatory diseases described in humans such as Familial Mediterranean Fever, Tumor necrosis factor Receptor – Associated Periodic Syndrome (TRAPS), Cryopyrin – Associated Periodic Syndrome (CAPS) and others. These are lumped together into Hereditary Recurrent Fever Syndromes (HRFS). These are all diseases which are due to mutations in the genes which regulate the production of inflammatory cytokines (chemical messengers) such as those in the interleukin family. FSF dogs are in a constant state of inflammation with high levels of inflammatory proteins such as IL-6, IL-1β, acute phase reactant proteins, and serum amyloid A (SAA) protein, among others. The development of systemic reactive amyloidosis is a potential complication of all the autoinflammatory diseases.
  5. FSF is more complicated in Shar-Pei due to a genetic mutation which results in Hereditary Cutaneous Hyaluranosis (HCH) – grossly seen as the excessive wrinkles which define the breed. The genetic defect results in over-production of hyaluronan (mucin). Low-molecular weight break down products of hyaluronan metabolism are pro-inflammatory and exacerbate the pro-inflammatory process involved in FSF. Hyaluronan is a normal substance in the body making up the intercellular matrix or scaffolding between cells. Based on its cellular and water content it can present as a free flowing gelatinous material to something as firm as cartilage. Recently a mutation upstream of the HAS2 gene on chromosome13 has been discovered. The mutation is known as the “meatmouth” mutation and is a count number variation (CNV) consisting of multiple copies of a regulatory gene controlling hyaluronan synthesis. Increased levels of hyaluronan are associated with a tendency to develop FSF and amyloidosis. Research is continuing to focus on this mutation in the hope of developing a blood test to determine an individual’s risk of developing FSF +/- amyloidosis.
  6. The tendency to develop amyloidosis may also represent an additional defect that is probably present throughout the canine genome in all breeds of dogs. Amyloidosis develops in the presence of chronic inflammatory diseases such as heartworm, tuberculosis, systemic fungal diseases, chronic bacterial infections and cancer. FSF and hyaluronosis are built-in triggers for the development of amyloidosis and account for the increased susceptibility of the breed to this complication.
  7. Pedigree studies indicate that FSF is an inherited disorder in the Shar-Pei probably as an autosomal recessive trait. Survey results have indicated that as many as 23% of Shar-Pei experience fevers of unknown origin. Shar-Pei with FSF have increased levels of the cytokine Interleukin-6 (IL-6). IL-6 is involved with the fever response 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.
  8. Shar-Pei with FSF are at risk from early death from systemic amyloidosis. About 5% 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).
  9. Early on, FSF in Shar-Pei was hypothesized to be an animal model for Familial Mediterranean Fever in humans. Recent work indicates this is not true, although FSF is very similar to FMF in man.

Laboratory Findings: Unfortunately there are no blood tests, 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. 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 (325mg) is given every 6- 12 hours for the first 24 hours and then twice a day for 3-5 days thereafter. It is important to continue treatment for several days flowing resolution of the episode to prevent rebound fever. In rare cases where aspirin doesn’t work or for extremely high fevers, dipyrone is given. Other NSAIDs may also be used but response may be a little unpredictable. 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. I currently recommend stopping colchicine therapy during an FSF episode while aspirin or other NSAIDs are being used as there is increased risk of gastritis.

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 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 for 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 levels 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 changes related to kidney failure. Increased water consumption, increased urination are the clinical signs associated with a loss of concentrating ability, but these signs are often not recognized. I also think it is wise to do a blood panel every 6-12 months and certainly do one if 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. Amyloidosis is usually medullary in Shar-Pei but can manifest as a protein-losing nephropathy and UPC ratios and treatment with ACE –inhibitors may be necessary.

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 at 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 the 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.(6/09/09)


shows swelling of the left hock. The hock is erythematosus and very painful. This is known as Swollen Hock Syndrome (SHS) in Shar-Pei circles. This term should only be used in dogs with the fever characteristic for FSF. Other causes of a swollen hock without fever are mucin accumulation (“socks”), allergic reaction, and cellulitis.

shows the characteristic stance of these dogs.

Typical fever associated with FSF

This figure illustrates that in less common cases the carpus is affected and rarely there can also be a swollen, painful lip or muzzle.

This figure illustrates a kidney affected by amyloidosis
  1. Rivas AL, Tintle L, et al: A canine febrile disorder associated with elevated interleukin-6, Clinical Immunol Immunopathol 64:36-45, 1992.
  2. Tintle, L: Familial Shar-Pei fever and familial amyloidosis of Chinese Shar-Pei dogs:http://www.royalsharpei.com/amyloidosis.htm 
  3. DiBartola SP, et al: Familial renal amyloidosis in Chinese Shar-Pei dogs, J Am Vet Med Assoc204:1212-1216, 1994.
  4. Olsson M, Meadows JRS, Truvé K, Rosengren Pielberg G, Puppo F, et al. (2011) A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs. PLoS Genet 7(3): e1001332.doi:10.1371/journal.pgen.1001332

© Jeff Vidt, DVM (12/2/12)

Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com and www.drjwv.com Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

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Deflated Muzzle, by Dr. Jeff Vidt

One of the major defining physical characteristics of the Chinese Shar-Pei is the large muzzle. This is due to the hyaluronan levels in the breed which contributes to the wrinkling, large padded muzzle and cutaneous mucinosis. All Shar-Pei can deflate to some degree although some have a more padded muzzle than others and the deflation would be more noticeable. It may be a good idea to measure the circumference of your dog’s muzzle using a sewing flexible tape measure. Muzzle deflation is caused by decreased hyaluronan production and there are three causes:

  1. Anti-inflammatory drug therapy is a major cause. This occurs because these drugs directly decrease hyaluronan production. Drugs known to cause deflated muzzles include:
    • NSAIDs –such as aspirin, carprofen (Rimadyl™), ketoprofen (Ketofen™), Etodolac (Etogesic™), acetaminophen (Tylenol™), deracoxib Deramaxx™), tepoxalin (Zubrin™), firocoxib (Previcox™), Piroxicam(Feldene™), meloxicam(Metacam™) and others.
    • Steroids –prednisolone, prednisone, dexamethasone, others.
    • Antihistamines –chlorpheniramine, diphenhydramine (Benadryl®), others.
  2. Stress –the release of substances related to stress will also deflate the muzzle. Stress should not always be thought of in terms negative things but any change in the dog’s normal routine can be thought of as stress. Positive stresses may consist of over activity, heat cycles, new people in the household, etc.
  3. Illness — This is the most important cause of deflated muzzle and one that Shar-Pei owners need to be very aware of. Think of the muzzle in this breed as the pop-up timer on the Thanksgiving turkey. When the muzzle deflates something is wrong and you should see your veterinarian quickly. FSF is a common cause of deflated muzzle as is kidney failure.

Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com and www.drjwv.com Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

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Streptococcal Toxic Shock Syndrome

While the vast majority of the episodes of Familial Shar-Pei Fever (FSF) seen in Shar-Pei run a fairly benign course there are occasional exceptions which can have life-threatening consequences. Over the last few years Streptococcal Toxic Shock Syndrome (STSS) has been seen more frequently as a complication of FSF in the Chinese Shar-Pei. STSS involves infection with a group G streptococcus called Streptococcus canis. In the Shar-Pei cases I’ve seen this streptococcal infection is a rapidly progressing, highly invasive process which results in a necrotizing faciitis and/or STSS leading to a shock-like syndrome and multiorgan failure. If not recognized early STSS can lead to death in 24 hours or less. A similar syndrome has been seen in human medicine, the so-called “flesheating bacteria”.

Necrotizing Faciitis

I consider this a localized form of streptococcal infection. Dogs with NF tend to develop extensive soft tissue sloughing along fascial planes. Fascia is dense connective tissue which covers the muscles. Usually this syndrome presents as large areas of skin and the underlying fatty tissue dying and peeling away, hence it has been called “flesh eating bacteria”. Many of these dogs will survive with debridement or clearing away of the dead tissue, but healing is prolonged and skin grafts are often necessary. Long-term management is intense with frequent bandage changes, cleaning of the wounds, antibiotic therapy and the need for multiple anesthetic procedures to repair and reconstruct the damaged areas. The areas I’ve seen involved are often the hock joints, the flanks and the abdominal skin.

Streptococcal Toxic Shock Syndrome

STSS seems to be a generalized or systemic form of streptococcal infection. Streptococcus canis in a potent exotoxin producer and it is thought that in cases of STSS the toxin may be responsible for the rapid progression of sepsis, shock and multiorgan failure (MODS) in cases of CSTSS. On necropsy these dogs show severe edema of the gastrointestinal tract, congestion of multiple organs, severe pulmonary (lung) congestion and evidence of thromboembolism (blood clots) all pointing to shock due to sepsis or toxemia. These dogs typically die within 24-48 hours in spite of aggressive fluid therapy, antibiotic treatment and intensive supportive care.

Recent information indicates that Streptococcus has the ability to produce hyaluronan lyases (similar to hyaluronidase in mammals) which are enzymes that can break down hyaluronan. We now know that low molecular weight HA has significant proinflammatory properties which may contribute to the severe vasculitis and tissue damage in STSS.

Streptococcal pyrogenic exotoxins A and B induce production of tumor necrosis factor –α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 suggesting that TNF could mediate fever, shock and tissue injury in cases of STSS. One of the virulence factors, M proteins, contribute to invasiveness through its ability to impede phagocytosis of streptococci by polymorphonuclear leukocytes. Data suggest that the streptococcal exotoxin can stimulate T-cell responses through their ability to bind to both Class II major histocompatibility complex of antigen presenting cells and the Vβ region of the T-cell receptor. The net effect would be to induce T-cell stimulation with the production of cytokines capable of mediating shock and tissue injury.

Clinical signs in the localized form of STSS, necrotizing fasciitis, consist of areas of skin bruising, dead skin and/or areas of sloughing where the skin is falling away. Usually there is a pus discharge from these areas. The dogs are very painful, running a high temperature, depressed and, in general, sick dogs. Often there is a history of an FSF episode, dog fight wounds, or other traumatic event. In the generalized or systemic form of STSS symptoms have a much more rapid onset and are more shock-like such as severe weakness, rapid heart rate, pale mucous membranes, extreme pain, collapse, coma and acute death. The lungs seem to be the primary site affected. Many of these dogs develop DIC (disseminated intravascular coagulation) which rapidly leads to multiple organ dysfunction syndrome (MODS) and death despite heroic efforts at treatment.

The emergence of this disease has been attributed to the popularity of fluroquinolones for use in dogs. It has been shown that enrofloxacin can cause a bacteriophage-induced lysis of S. canis and superantigen expression which induces T-cell proliferation and excessive release of host cytokines with potentially lethal effects.
Ingrey KT, Ren J, Prescott JF. A Fluoroquinolone Induces a Novel Mitogen-Encoding Bacteriophage in Streptococcus canis. Infection and Immunity, June 2003: pp. 3028-3033.

The cause of this condition is unknown. It is known that Streptococcus canis can be part of the normal bacterial flora of the dog and that NF and STSS have occurred in other breed. Predisposing factors in the Shar-Pei may be related to:

  1. The increased amounts of mucin in the subcutaneous tissues.
  2. The prevalence of FSF in the breed.
  3. The prevalence of dog fights and bite wounds in the breed.
  4. An increase in skin laxity resulting in more trauma.
  5. Immune system insufficiencies.
  6. Perhaps an increased virulence of some strain of Streptococcus canis.

Diagnosis is based on the history of previous trauma or FSF episode, bacterial culture and sensitivity of discharges or tissue samples, and clinical signs. One important point is that the organism is often resistant to enrofloxicin (Baytril®) and the aminoglycosides such as Amikacin® and Gentocin®. Consider the use of multiple antibiotic therapy with agents such as Clavamox®, cephalexin, clindamycin, lincomycin, erythromycin, penicillin and the potentiated sulfas. Of course, the best approach is based on sensitivity information from a culture, but that takes some time to generate.

Treatment of the necrotizing fasciitis involves appropriate antibiotic selection and administration, and basic wound care of the affected areas. I have seen dogs have recurrence of necrotizing fasciitis with repeat FSF episodes. Usually they seem to slough out the same area every time. Treatment of the STSS involves intensive care with intravenous fluid therapy, shock treatment with IV antibiotics, pain management, steroids (?), and intensive monitoring for the development of DIC, etc. At this time the prognosis for systemic STSS must be considered very poor.

Increased owner awareness of NF and STSS, rapid initiation of appropriate antibiotic therapy and intensive supportive care are the keys to survival in this condition. An excellent article on STSS appeared in the October 15, 1996 issue of the Journal of the American Veterinary Medical Association, Volume 209, Number 8, pages 1421-1426 by C. Miller, J. Prescott, K. Mathews et al. entitled “Streptococcal Toxic Shock Syndrome in Dogs”.

At this time there is no evidence suggest that humans are susceptible to infection by group G Strep. However all humans involved in the care of these dogs should take common sense precautions such as the use of exam gloves, proper disposal of bandage materials, personal hygiene, etc. I would not recommend that these dogs be cared for by immunocompromised individuals, children, the elderly or physically ill people.
Jeff Vidt, DVM
12/2/2012

Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com and www.drjwv.com. Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

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Blindness in the Chinese Shar-Pei By Jeff Vidt, DVM

Blindness can and does occur in the Shar-Pei. One of the major causes is uncorrected entropion. If entropion (rolling in of the eyelids) is not corrected several changes occur which can lead to blindness. Entropion can lead to severe corneal damage, ulceration and ultimately, corneal scarring. The corneal response to chronic irritation is to protect itself by forming scar tissue on its surface. This tissue appears cloudy, often with a brown pigment. Blood vessels can be seen on the surface and the cornea appears rough and irregular. With the clear cornea rendered opaque the dog is functionally blind. Drying of the cornea can also cause similar changes and is seen in a condition called keratoconjunctivitis sicca (KCS). In this condition, there is a decrease in tear production primarily in the lacrimal gland. This can occur as a sequela to viral infection such as distemper, herpes virus and others or as a primary immune-mediated destruction of the lacrimal gland. The decrease in tear production results in drying of the cornea and the formation of scar tissue as a protective response. A Schirmer Tear Test, which measures tear production, can be easily done to diagnose this condition and treatment is possible. KCS also seems to occur more often in those dogs that have had “cherry eye” or prolapse of the gland of the third eyelid in which the gland was removed instead of tacked back into position. Tacking is much preferred in treating cherry eye for this reason. Other causes of blindness we will discuss are glaucoma, optic neuritis, Sudden Acquired Retinal Degeneration (SARD) and retinal detachment/hemorrhage. Before we get into a discussion of some of the other diseases which can cause blindness we need to review the anatomy and physiology of the eye a little bit.

The first figure shows a cross-section of the eyeball. The major features I want to emphasize are the cornea (8), the iris(7), the lens (3), the retina (15) and the optic nerve (18). Vision is really dependent on several major areas:

  1. The cornea must be clear and unobstructed to allow light and the visual image to enter the eyeball.
  2. The lens likewise must be clear to allow light and the image to enter the eyeball.
  3. The retina must be functional to capture the visual image and process it.
  4. The optic nerve must be intact to transmit the visual image from the retina to the brain.
  5. The brain must be functional to process the electrical impulses from the retina and allow a visual image to be “seen” by the dog.

I realize this is a very simplistic explanation of a very complex process. The retina itself is composed of several layers consisting of supporting tissue, blood supply, nervous connections, rods (night vision), cones (color vision), etc. The basic function of the retina is to take the visual image projected on the retina and convert it to electrical impulses, which can be transmitted and processed by the brain.

Sudden Acquired Retinal Degeneration (SARD)

Sudden acquired retinal degeneration (SARD) is a retinal disease seen in Shar-Pei as well as other breeds of dogs. Remember the retina is the photoreceptor layer of the eye, which is responsible for converting visual images to electrical signals. These signals are transmitted to the brain where the image is processed. This condition leads to a very sudden onset of blindness, which occurs over a period of a few days to several weeks.

The retina is normal when viewed with an ophthalmoscope, but there is a loss of photoreceptor activity as evidenced by a diminished electroretinogram (ERG). The ERG is a test which measures the electrical activity of the retina. Synonyms for SARD are “toxic metabolic retinopathy” and “silent retina syndrome”. Shar-Pei with SARD are usually middle-aged females many of whom are overweight and may have symptoms of Cushing’s disease or hyperadrenocorticism – increased water consumption, increased urination, panting, increased appetite, etc. Often there are laboratory changes in the blood tests consistent with hyperadrenocorticism such as an increase in liver tests such as the alkaline phosphatase, alanine transaminase (used to be the SGPT) and cholesterol. Some of these dogs will have abnormal ACTH stimulation or low-dose dexamethasone suppression tests confirming hyperadrenocorticism. I must emphasize that a link between SARD and hyperadrenocorticism has not been proven although I would recommend that all Shar-Pei with SARD be evaluated for hyperadrenocorticism. Treatment for hyperadrenocorticism will not result in a return of vision. Not all dogs with SARD have hyperadrenocorticism, but the percentage is higher than in the normal dog population. The cause of SARD is not known at this time, but one theory suggests that perhaps an abnormal corticosteroid has a role in the disease process as well as being involved in the hyperadrenocorticism. There is no treatment for SARD and the dog will be permanently blind. Your veterinarian should rule out other causes of blindness in Shar-Pei which include glaucoma, retinal detachment (sometimes accompanying hypertension with kidney disease), pigmentary keratitis, optic neuritis, etc.

This is an inflammatory condition of the optic nerve which can result in acute, bilateral loss of vision. Degenerative changes in the optic nerve can result in similar symptoms and are more correctly termed optic neuropathy. If the optic nerve is affected as it leaves the back of the retina changes can be observed on evaluating the retina with an ophthalmoscope. If the optic nerve is affected behind the eyeball the retina may appear normal. Causes include infectious diseases such as canine distemper, toxoplasmosis, and others, various types of cancer such as lymphoma and tumors involving the orbit or bony eyeball socket, vitamin A deficiency, trauma, other diseases of the orbit such as abscesses and cellulitis and unknown causes. The vast majority of optic neuritis in dogs is due to unknown causes. Early treatment is imperative and involves the use of steroids. The prognosis is guarded and recurrences are common. Glaucoma Glaucoma is simply an increase in fluid pressure within the eyeball. Figure 2 is a crosssection of the eyeball showing the flow of aqueous fluid in the eye. The production and drainage of this fluid is largely responsible for the pressure inside the eye. Key elements are the ciliary body (4) which produces the aqueous fluid which flows through the pupil into the anterior chamber (1) and drains out the drainage angle (7). Glaucoma is classified as primary or secondary. Primary glaucoma occurs in the Shar-Pei due to a genetically preprogrammed narrowing of the drainage angle. This interferes with drainage of the aqueous fluid and causes an increase in intraocular pressure. Secondary glaucoma occurs in the Shar-Pei as a result of lens luxation. This is inherited as a simple autosomal recessive trait in the Shar-Pei (Primary lens luxation in the Chinese Shar-Pei: clinical and hereditary characteristics; Lazarus JA, Pickett JP, and Champagne ES; Veterinary Ophthalmology (1998)1, 101-107). When the lens (2) shifts out of normal position it FIGURE 2 usually shifts forward obstructing the pupil and interfering with drainage of aqueous fluid and causing a rise in the intraocular pressure. Clinical signs include conjunctivitis (“bloodshot eyes”), cloudy cornea, swollen (buphthalmos) painful eyes, squinting, increases tearing, and a fixed, dilated pupil. Diagnosis is based on measurement of intraocular pressure (IOP). Normal values in the dog are 15-25 mmHg. Anything above 25 mmHg is abnormal and glaucoma treatment should be initiated immediately – the increased pressure can cause lose of vision within 4-24 hours depending on how rapidly the pressure increases. One problem I see in Shar-Pei is that early on they may have intermittent pressure spikes and be normal in between these episodes. Also squinting may be mistaken for entropion. Medical treatment, in the dog, is usually not successful long term. Surgical options, in a visual eye, involve destroying some of the ciliary body by freezing (cryothermy) or laser destruction (laser cyclophotocoagulation), or placing a glaucoma shunt. In a blind eye in which the pressure can’t be controlled medically options include removing the eyeball, using an intraocular prosthesis or injecting the eyeball with gentamicin to destroy ciliary tissue. These are procedures done by a veterinary ophthalmologist. This is a common cause of blindness in the Chinese Shar-Pei.

Retinal Detachment/Hemorrhage

Dogs do develop secondary hypertension or high blood pressure. Primary hypertension, as commonly occurs in humans, has not been documented in the dog, as yet. Increased blood pressure often occurs secondary to kidney disease, primarily glomerulonephritis, Cushing’s disease, and heart disease. High blood pressure can result in bleeding into the retina due to rupture of the tiny blood vessels located there. This hemorrhage can lead to damage with subsequent scarring of the retina or blood building up behind the retina and causing a detachment. Blindness can result. Retinal detachment can also occur as a result of head trauma. This may be treated with anti-inflammatory medication, antihypertensive medication and treatment of the primary disease problem. Before discussion of the next ocular condition it is necessary to review the anatomy of the retina. The major area of interest is the layer containing the rods and cones. Rods are very sensitive, but are less capable of fine vision discrimination and function in night vision. Cones are less light sensitive, but enable fine vision discrimination and function primarily in day vision. The rods are primarily located in the peripheral retina and the cones are located primarily in the central retina. In some species (such as humans) the cones contain pigments which allow for color vision. Some nocturnal species have only rods in their retinas.

Progressive Retinal Atrophy (PRA)

I have not personally heard of this group of ocular diseases in the Shar-Pei, but have heard references to the Shar-Pei in discussions of PRA. PRA is also referred to as Progressive Retinal Degeneration. This disorder is classified into 3 broad categories. PRA Type 1 also known as generalized progressive retinal atrophy can occur in any breed of dog even if the disease is not a severe problem in the breed. Here the rods undergo early degeneration resulting in loss of night vision followed by degeneration of the cones resulting in loss of day vision. Age of onset, rate of progression, severity, etc. varies and is unpredictable. In the breeds in which the genetics have been worked out it is inherited as a simple autosomal recessive trait. PRA Type 2, also known as central progressive retinal atrophy, primarily affects working and hunting breeds. Visual deficits in this type of PRA are generally less severe and don’t usually occur until middle age. PRA Type 2 is a pigment epithelial dystrophy, which progresses to involve the entire retina. Total blindness is uncommon. PRA Type 3 is a simple autosomal recessive disorder, which affects the cones in the retina of the Alaskan malamute and the miniature poodle resulting in day blindness. There is no treatment for the various types of PRA. Blindness in the Shar-Pei is not hopeless. Dogs adjust very well to blindness and can function normally after an adjustment period. I was very encouraged when I met two blind Shar-Pei at the 1999 Nationals just held in Moline, Illinois. Both were blind due to glaucoma. I also have a blind Shar-Pei of my own due to glaucoma and she functions very well in her home environment.

Simple rules I’ve found are:

  1. Don’t change the environment much. Dogs memorize the layout of the house and yard.
  2. Keep blind dogs on a leash in a new environment. Help them with stairs, doors and other obstacles.
  3. Watch blind dogs around other dogs. Dogs don’t always realize blind dogs can’t see and may fight when they get bumped into or stared at by a blind dog.
  4. While their hearing is unaffected, blind dogs seem to have some trouble in orienting to sound.

Blindness is not unique to Shar-Pei and owners need to be aware that blind dogs can have an excellent quality of life. They need us to be their eyes.

Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com  and www.drjwv.com  Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

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Eye Tacking By Jeff Vidt, DVM

Puppies open their eyes at about 7 – 10 days of age. In Shar-Pei, this is often when the first symptoms of entropion appear. Typically the puppies open their eyes, but quickly they begin squinting and closing them. Often there is a mucous eye discharge and these puppies usually don’t eat well or gain weight like their littermates. EYETACKING is a temporary measure in which sutures (stitches) are placed in the eye lids to roll the lids “out” of the eyeball. Often this can be done without anesthesia in very young puppies (2-4 weeks of age). Sometimes gas anesthesia is used. Nylon sutures are placed in the eyelids which opens the eyes. I usually use 4-0 nylon with a small cutting needle like a CS-1). Often an antibiotic eye ointment is dispensed to help heal any corneal ulcers and prevent secondary bacterial infections.These sutures are left in place for as long as possible – up to 4 weeks in some cases. The tacks can be replaceed as needed until a permanent repair procedure can be done. If the sutures loosen up or are causing problems, they can be removed. Eye tacking can result in permanent repair of entropion, but its primary goal is to prevent serious eye damage until the pup is old enough to undergo permanent entropion repair – around 6-8 months of age. Puppies who have their eyes tacked may or may not need permanent entropion repair later on – there is not much correlation between the two.

ENTROPION IN YOUNG PUPPIES CAN RESULT IN CORNEAL ULCERATION AND IS A MEDICAL EMERGENCY – SEE YOUR VET IMMEDIATELY!


Appearance of lower lid entropion in a Chinese Shar-Pei. All four lids may be affected.

Insertion of the vertical mattress sutures. The first bite is taken near the lid margin.

The sutures are tied, with the knots away from the eye. The suture can be removed after 10 to 14 days. If they loosen or pull out, replace as necessary.

(Many thanks to Jo Ann Redditt for allowing me to use illustrations from her book “Understanding the Chinese Shar-Pei” published by Orient Publications, P.O. Box 6468, Arlington, VA 22206)

Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com and www.drjwv.com Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

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Separation Anxiety by Jeff Vidt, DVM

Separation anxiety is just one of a wide variety of behavior disorders which can affect dogs in general. These include obsessive-compulsive disorders, various phobias, panic attacks, etc. These disorders are probably not new conditions, but research has now allowed us to name them and apply a combination of drug therapy, behavior modification techniques, and training methods to treat them. Separation anxiety appears to be one of the more common behavior disorders that veterinarians encounter. Symptoms of separation anxiety commonly occur in the owners absence and include:

  1. Elimination — urinating and/or defecating indoors when the owner is gone.
  2. Destruction — chewing woodwork, furniture, carpeting, etc. when the owner is not in the house. This also includes clawing or digging floors, walls, and doors. Damage also can occur to windows, drapes, and blinds.
  3. Vocalization — barking, whining, crying in the owners absence.
  4. Other signs — including loss of appetite, depression, diarrhea, vomiting, excessive licking, increased salivation, decreased activity, pacing, circling and trembling.
  5. “Velcro”dogs— they stay physically close to their owners at all times. These dogs beg for attention and greet their owners over-enthusiastically. Treatment involves the combination of behavior modification with or without drug therapy. Behavior modification consists of abortion of inappropriate behavior, teaching new behaviors, and general relaxation techniques.

BEHAVIOR MODIFICATION

Teach the dog not to be anxious when left alone. This is done by utilizing the “sit”, “stay” and “relax” commands while the owner does a variety of routine chores around the house — some of which may upset the dog (vacuum the house). The dog should eventually be able to do these behaviors without reacting adversely — in the house, outside the house, and for all family members. Next, teach the dog to be left alone for gradually increasing periods of time. Here consider taking the dog to work, hiring a pet sitter, or kenneling the dog during the day. In addition, the dog must respond to programs designed to support and encourage deferential behavior throughout the day i.e. less “babying” behavior. For example, the owner should only interact with the pet only at the owner’s initiative and when the dog is relaxed. Obedience training would also be useful here as well. All these things foster independence in the dog. Crate the dog or isolate it in a safe room — an area where the dog feels safe and secure.. Usually this area is brightly lit with a radio or TV on. Also have a signal that will tell the dog 15-20 minutes before you return that you’ll becoming back (a light on a timer,etc.).Some dogs do better outside or if they can see outside. Identify cues that make your dog realize you are about to leave. These cues may include putting on makeup, dressing in work clothes, picking up car keys, making a lunch, etc. Try to vary the cues by wearing different clothes, leave by a different door, water the plants before leaving — anything to change the pattern so the dog can’t know when you are leaving the house. This will help the dog to become indifferent to departure cues.

MEDICATION

Most of the medications for separation anxiety are tricyclic antidepressants (TCA) which have selective serotonin reuptake inhibitor (SSRI) activity. They affect two brain neurotransmitters, serotonin and norepinephrine, and increase their concentration in the brain. The end result is a decrease in anxiety and an increase in learning ability. The only licensed medication for the treatment of separation anxiety at this time is Clomicalm® (clomipramine). Medication should never be used by itself — the drugs should always be combined with behavior modification.

Using the above therapies together often decreases the symptoms or eliminates them altogether. Often the drug therapy can be dropped and behavior modification alone can maintain control of the condition. To say that the dog is “cured” is probably not correct — one has to think in terms of “control”.

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Tight Lip Syndrome by Jeff Vidt, DVM

Shar-Pei pups often have a condition called “tight lip syndrome” in which the lower lip pushes against the lower incisor (front) teeth or may even extend to cover those teeth. It is felt by some practitioners that the soft tissue of the lower lip impedes the growth of the lower jaw (mandible) resulting in an underbite. I don’t think that happens as I don’t believe soft tissue can impede bone growth but the lip pressure does cause the lower incisor teeth to angle back towards the mouth and it appears the bite is off. Rarely (I’ve not seen a case) the tight lip can interfere with eating and that is a problem. Two types of surgical repair are available. Surgery usually should be done early – around 3 months of age. One surgery involves resection of the skin of the chin. In this procedure the lower lip is pulled ventrally to expose the lower incisors. When this is done a fold of skin is created on the chin and an elliptical incision is made through the skin and subcutaneous tissue and the fold is removed. When the subcutaneous tissue and the cut edges of the skin are opposed the lower incisor teeth should remain exposed. A variation of this procedure involves removing a triangular piece of skin from the ventral chin with the base of the triangle parallel to the lower incisors. When the triangle is closed the lower lip is everted.

The second procedure is a cheiloplasty procedure. Here the lower lip is separated from the chin so the lip can heal in a more normal position. With the puppy on its back the lower lip is pulled down to expose the lower incisor teeth an incision is made along the mucogingival junction from the first premolar tooth on one side to the first premolar tooth on the other side. The subcutaneous tissue is stripped from the mandible using a periosteal elevator. The tightness of the lip determines the extent of dissection required. The lip should hang just ventral to the mucogingival junction. If it doesn’t, additional length of lip should be dissected from the mandible. No sutures are placed. The owner must run their finger around the created pocket between the lip and mandible daily. This has to be done to prevent the healing tissues from pulling the lip back into normal position. The wound heals by secondary intention healing.

Some veterinarians prefer the cheiloplasty procedure over the chin skin resection procedure – they feel the chin skin resection results in decreased flexibility of the skin of the chin which may prevent normal lengthening of the mandible. Also bear in mind this is a cosmetic surgery and these dogs cannot be shown in the American Kennel Club

Note: Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com and www.drjwv.com Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

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Mast Cell Cancer

MAST CELL CANCER seems to be a particularly aggressive and troublesome problem in the Shar-Pei breed. The following discussion hopefully will provide you with some useful information.

  1. CAUSE: Mast cells are a normal component of the body. These cells contain granules in theircytoplasm which contain heparin (an anticoagulant), serotonin (an inflammatory mediator), histamine, bradykinins, TNF-α and a number of other substances. The release of these vasodilator, nociceptive and proinflammatorymolecules cause inflammation, itching, edema, vasodilation and attract other cells such as macrophages and white blood cells to the area. This response is usually helpful in responding to allergic reactions, foreign objects, infection, etc. This also explains why mast cell tumors tend to be swollen, inflamed, ulcerated and itchy. Often a “blush” or skin redness around the tumor is apparent (Darier’s sign). Shar-Pei have a higher than normal population of mast cells in their subcutaneous tissue which may partially explain the frequency and aggressiveness of these tumors in our breed. Due to the increased mucin in the subcutaneous tissues of Shar-Pei spread of mast cells may occur more easily as well — the mucin may also hinder the identification of the tumor margins and thus the complete surgical removal of mast cell tumors. There appears to be an inherited or genetic aspect to mast cell cancer as well as it appears more often in some lines of Shar-Pei. There also seems to be a connection between eosinophilic granulomas and mast cell cancer in some individuals. I have removed masses which on histopath read out as eosinophilic granulomas and recurred as mast cell tumors. The ultimate cause of this type of cancer is unknown. It is the most common skin tumor in dogs accounting for about 20% of all reported skin tumors. Dogs with mast cell tumors have increased levels of circulating histamine, which may lead to GI ulcers and allergic reactions.
  2. SIGNS: Owners may report seeing a mass that grows and shrinks repeatedly – this is usually due to local histamine release that leads to intermittent swelling. Some dogs have a recent rapid tumor growth while others have a tumor that has been present and unchanged for months to years. There is not one characteristic appearance for mast cell tumors – often skin nodules are reddened, itchy and ulcerated. These can be confused with histiocytomas, a benign growth which often regresses on its own in 4-8 weeks and which are often seen in Shar-Pei at any age. In Shar-Pei cutaneous mastocytosis may be seen in which large areas of skin are involved without an actual tumor being present – often this is confused with allergic skin disease or demodecosis. The importance of fine-needle aspiration and cytology cannot be over-emphasized. Subcutaneous nodules (under the skin) can be confused with lipomas, benign fatty tumors.
  3. DIAGNOSIS: Any lump or bump on a Shar-Pei is suspicious. Mast cell tumors are often confused with histiocytoma, a benign tumor of the skin which also has a high incidence in the Shar-Pei. If the mass is large enough a fine-needle aspirate may be done to identify the mast cells. Often the tumor must be identified after it is removed. A particularly troublesome variation of mast cell tumor known as AGRANULAR SPINDELOID MAST CELL or ANAPLASTIC MAST CELL is seen in the Shar-Pei and is characterized by mast cells with few or no granules. This is a very aggressive form of mast cell and can be confused with other tumor types. The most commonly used grading system for mast cell has a Grade 1 which indicates a well-differentiated mast cell type and is considered least malignant, Grade 2 which is an intermediate type and which I consider malignant in the Shar-Pei and a Grade 3 which is an undifferentiated type of mast cell and definitely considered malignant.
  4. TREATMENT: Surgical removal of the tumor with wide normal margins is the current recommended treatment. Obviously the smaller the tumor the more easily this is accomplished. Location of the mass also determines how successful surgery will be. I often recommend referral to a veterinary oncologist (cancer specialist) or a veterinary cancer center. At the cancer center there is usually a group consisting of a veterinary surgeon, veterinary oncologist and often, radiation treatment facilities. The chemotherapeutic approach for mast cell cancer is not well worked out at this time and is an area of active research. Mast cells are radiation-sensitive and radiation therapy is often used as an adjunct to surgery. The Shar-Pei owner must decide early on how aggressive an approach they will seek. Local recurrence and spread of mast cell cancer often occurs within 4-6 months after surgery alone. The prognosis in the Shar-Pei is guarded to poor. I have seen mast cell cancer in Shar-Pei as young as 10 months. Chemotherapy often includes prednisolone in combination with other agents. Currently tyrosine kinase inhibitor therapy appears to be useful in the treatment of mast cell cancer.
  5. MASTOCYTOSIS: This is a form of mast cell cancer which is systemic and involves internal organs such as the liver, spleen, lymph nodes and GI tract. This can have a much poorer prognosis.
  6. PARANEOPLASTIC SYNDROME: This term denotes systemic signs which accompany certain types of cancer. The inflammatory response which often accompanies mast cell cancer can result in GI tract ulceration with vomiting and diarrhea, often with blood, as a consequence. Sometimes excessive manipu-lation of a mast cell tumor can result in massive degranulation of the tumor cells which can lead to a life-threatening systemic shock reaction. Most common is the localized swelling, draining and itching at the tumor site.
  7. PROGNOSIS: Mast cell tumors have extremely variable biologic behavior. Some are relatively benign and curable with local excision while others may be very aggressive, spread rapidly (metastasis) and are fatal. Sites for metastasis include regional lymph nodes, spleen, liber, bone marrow and skin – they rarely involve the lung. Negative prognostic factors:
    • Recent, rapid growth
    • Deep, fixed mass
    • Systemic signs: tarry stools, vomiting,etc.
    • Tumor location – poorer prognosis for tumors on the muzzle, inquinal/preputial areas and mucocutaneous junctions (mouth, anus, nail beds)
    • Regional lymph node metastasis
    • Internal spread
    • Histologic features – high grade tumor (grade3), high mitotic index (>5 mitotic figures/10 hpf), presence of c-kit mutation, high Ki-67 score (>1.8).

Ultrasonography can also be used to evaluate abdominal organs (spleen, liver, GI tract and lymph nodes for metastatic mast cell disease

New Information:

Research conducted over the last several years has concentrated on the genetic aspects of mast cell cancer. KIT is a receptor protein located on mast cells which is encoded by the proto-oncogene c-kit. A gene normally encodes for a protein product which performs a specific function in the body and in many genetic diseases a gene mutation occurs which results in no protein being produced or an abnormal protein product which is either non-functional or has an abnormal function. In normal mast cells KIT signaling is critical for the normal development and function of mast cells. Mutations in c-kit result in KIT dysregulation which may promote uncontrolled growth or survival of mast cells. These mutations in c-kit have been discovered and consistent of tandem duplications in exons 11 and 12 of the gene. These exons encode for the juxtamembrane domain which prevents activation of KIT. It acts as an “on-off” switch if you will. These mutations cause a continuous “on” signal for KIT and appear to be associated with more aggressive mast cell tumors. Another study has demonstrated loss of intron 11 which is the region between exon 11 and 12 which occurs in canine mast cell tumors. This suggests that canine mast cell disease is probably the result of several different mutations in the c-kit region.

  1. London CA, Chien MB, Pfieff J, Downing S, Grahn RA. Genes, Dogs and Cancer: Emerging Concepts in Molecular Diagnosis and Therapy. Conference May, 2001.
  2. Reguera MJ, Ferrer L, Rabanal RM. Evaluation of an intron deletion in the c-kit gene of canine mast cell tumors. Am J Vet Res 63.9:1257-1261.
  3. Downing S, Chien MB, Kass PH, Moore PF, London CA. Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. Am J Vet Res 63.12:1718-1723.
  4. Dank G, Chien MB, London CA. Activating mutations in the catalytic or juxtamembrane domain of c-kit in splenic mast cell tumors of cats. Am J Vet Res 63.8:1129-1133.

Additional research has looked at the serine proteases α-chymase and tryptase which are selectively concentrated in secretory granules of mast cells. These serine proteases may potentially serve as markers of the biological aggressiveness of mast cell tumors 5.

  1. Serine Proteases in Mast Cell Disease. Timothy M. Fan, DVM, DACVIM, Proceedings of the 20th Annual AVCIM Forum, Dallas TX, May 2002, pages 414-415.

As a direct result of some of the above research projects some therapeutic trials have been initiated. Since KIT is classified as a receptor tyrosine kinase it can be inhibited by agents called kinase inhibitors. Several of these drugs are in the pipeline. One has been developed for humans called Gleevac® (STI571) which blocks the ATP binding site of KIT and inhibits KIT signaling. Liver toxicity has been a problem in animals with this drug. Another class of kinase inhibitors called the indolinone kinase inhibitors (SU5416, SU6668) are currently being studied in humans. These agents are capable of disrupting the function of all forms of mutant KIT. Remissions of up to 6 months have been induced by these agents in some cases of mast cell cancer in dogs but relapses occur 6.

  1. Kinase Inhibitors in Cancer Therapy. Dr. Cheryl London, DVM, PhD, DACVIM. Proceedings of the 20th Annual ACVIM Forum, Dallas TX, May 2002, pages 436-438.

Another recent article has looked at mast cell cancer and plasma histamine concentrations. Mast cell granules contain histamine, heparin and proteolytic enzymes. Release of these granule substances can cause gastroduodenal ulceration/perforation, delayed wound healing, hypotensive shock, local ulceration/swelling and coagulation abnormalities. Hyperhistaminemia is a major factor contributing to gastroduodenal ulceration and perforation. Histamine release from mast cell tumors can occur due to spontaneous release, aggressive manipulation (especially during surgery), chemotherapy and radiation therapy. Plasma histamine concentration is one factor related to mast cell disease progression. It also appears related to tumor dissemination. Up to 80% of dogs with progressive mast cell cancer have gastroduodenal ulceration. Lastly, dogs that don’t respond to H2 –blockers have marked hyperhistaminemia. This study concludes that plasma histamine concentrations may provide useful diagnostic, prognostic and therapeutic information 7.

  1. Ishiguro T, Kadosawa T, Takagi S, Kim G, Ohsaki T, Bosnakovski D, Okumura M, Fujinaga T. Relationship of Disease Progression and Plasma Histamine Concentrations in 11 Dogs withMast Cell Tumors. J Vet Intern Med 2003; 17.2:194-198.

The drug company Pfizer has plans to release a tyrosine kinase inhibitor for the veterinary market called Palladia® in late 2009 or early 2010. It will be labeled for use in mast cell cancer in the dog. No further information is available at this time.

Another potential modality in the treatment of mast cell cancer involves the use of mast cell stabilizers. One such drug is cromolyn sodium (Gastrocrom®). Another drug which inhibits mast cell histamine secretion is pentosanpolysulfate (Elmiron®, Cartrophen®). This is a synthetic, sulfated polysaccharide that has been approved for the treatment of interstitial cystitis (IC) – it may help replenish the defective glycoseaminoglycan layer in the bladder in this condition. A research paper indicates pentosanpolysulfate has a powerful dose-dependent inhibitory effect on mast cell release of histamine. 8

  1. Chiang G, Patra P, Letourneau R, Jeudy S, Boucher W, Green M, Sant GR, Theoharides TC. Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis. Department of Pharmacologyand Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts, USA.

Palladia® (toceranib phosphate) has been around for about 3 years now and here are some insights from the specialists who use it:

  1. Palladia® will be effective only in Grade II or Grade III mast cell tumors that are positive for the c-Kit gene mutation. It is important when a mast cell tumor is removed that it be tested for this genetic mutation. Only 28% of mast cell tumors are positive for this mutation.
  2. Palladia® should be used with the same precautions as any other chemotherapeutic drug. It can be nephrotoxic, may cause pancreatitis, low serum albumin levels, anemia, low white blood cell counts, etc. Dogs should be seen weekly for the first 6 weeks with CBC, blood panel and urine samples checked. The dosage of the drug should be adjusted or the drug discontinued if any of these side-effects are seen.
  3. Often it is best to start with a dosage about 25% less than the original dosage proposed by the manufacturer and often other drugs are added such as prednisone, antihistamines and H2-receptor antagonists such as Tagamet-HB®, Pepcid-AC® and others to minimize side effects.
  4. Another drug calledMasivet® (masitinib) is currently in clinical trials in Europe. This drug appears to have fewer side effects than Palladia®. It is now available in the U.S. as Kinavet®
  5. I have seen some promising results with the use of Palladia® in some of the mast cell cases I’ve personally referred to oncologists who have used it. It is an oral medication and can be given by owners at home – a distinct advantage over other chemotherapies.

Masivet® (Kinavet-CA1®)

  • Masivet® is the brand name for the tyrosine kinase inhibitor masitinib.
  • It specifically targets stem cell receptor c-Kit, PDGFR α and β, and LYN.
  • Particularly effective in controlling the proliferation, differentiation and degranulation of mast cells.
  • Useful in the treatment of mast cell dysfunctions.
  • In mast cell cancer treatment it is only used if the presence of a mutated of the receptor protein c-Kit in the tumor has been confirmed. Excessive action of c-Kit results in uncontrollable mast cell proliferation. Masivet® blocks receptors for c-Kit.
  • Dogs on Masivet® took longer for the tumor to get worse (median of 241days in treated dogs vs. median of 83 days in untreated dogs).
  • Survival rates at 12 and 24 months were significantly improved in dogs receiving this drug.
  • Tumor response at 6 months was predictive of long-term survival at 12 and 24 months.
  • First-line treatment with masitinib was more effective than placebo regardless of whether a c-kit mutation was present. Dogs that had received other therapy prior to masitinib, however, only responded if the c-kit mutation was present.
  • Masitinib effective in dogs with metastases.
  • Also significantly reduces the emergence of nodal and visceral metastasis.
  • Prevents the proliferation of tumor mast cells
  • Inhibits the phosphorylation of PDGF-α and β receptors as well as PDGFdependent cell proliferation.
  • Inhibits mast cell degranulation modulates inflammatory and immune responses.
  • Tablet sizes = 50mg. and 150mg.
  • Common side effects are diarrhea, vomiting and alopecia.
  • Dose is 12.5 mg/kg once a day.
  • Kinavet-CA1® — ABScience (in the United States)
  • Inhibits LYN kinase activity. Lyn has been associated in certain forms of TKI resistance and is associated with several different cancers.
  • Side-effects include non-regenerative anemia, decreased white blood cell counts, protein-losing nephropathy
  • Particularly effective in controlling the proliferation, differentiation and degranulation of mast cells.
  • Useful in the treatment of mast cell dysfunctions.
  • They play a key role in chronic inflammatory diseases such as allergies, atopic dermatitis, asthma and arthritis
  • Kinavet-CA1®Tablet sizes = 50mg. and 150mg.

More mast cell stuff:

  • c-kit is a receptor tyrosine kinase for stem cell factor (SCF). Stem cell factor stimulates mast cell growth.
  • Mutations in c-kit are: internal tandem duplications (ITD) within exons 11 and 12 of the c-kit gene. This is known as the exon 11 mutation.
  • When SCF binds to unmutated c-kit, the cytoplasmic portion of the receptor undergoes autophosphorylation. In the presence of the exon 11 ITD, the receptor is constitutively phosphorylated, regardless of whether SCF is present or not. The presence of the mutation is directly responsible for the uncontrolled proliferation of mast cells.
  • Other c-kit mutations: 12-base pair ITD in exon 8, single base pair change in exon 9, additional single base changes and rare deletions and insertions detected in exon 11 and exon 17.
  • Current methodology will not detect single base pair changes (false negatives?).
  • The standard methodology requires approximately 10% of the cells in the sample to be mast cells – not useful for detecting mets in draining lymph nodes or for residual disease detection.
  • First-line treatment with masitinib was more effective than placebo regardless of whether a c-kit mutation was present. Dogs that had received other therapy prior to masitinib, however, only responded if the c-kit mutation was present.
  • In another study, dogs with recurrent mast cell disease responded better to Palladia if they carried the exon 11 c-kit mutation than if they did not.
  • c-kit mutations can be used as a tumor fingerprint – determines if recurrent mast cell tumors are from the same clone (the same mutation).
  • Possibility of creating tumor-specific PCR primers based on the mutated sequence which could detect distant metastases and the presence of neoplastic cells in the blood and can even be used to quantify tumor cells.
  • c-kit mutations present in gastrointestinal stromal cell tumors (GISTs) also.
  • Detection of c-kit mutations in mast cell tumors is now routinely used for prognosis and guiding treatment. Most commonly, mutation status is determined together with immunohistochemical staining to examine proliferation markers and the cellular location of c-kit. These factors help establish prognosis and the need for additional therapy.

Avery AC. Molecular Diagnostics of Hematologic Malignancies in Small Animals. Vet Clin Small Anim 42 (2012) 97-110

I realize much of this new information will mean little to the reader but four points need to be made. First, the Chinese Shar-Pei Club of America Charitable Trust has been actively involved in funding much of this research in mast cell disease. I believe this function of the Charitable Trust is critical for our breed and I believe your continued donations to the Trust are critical for our breed as well. You won’t see breakthroughs in cancer research unless you have funding of that research. Second, there is a great deal of information sharing in the scientific community concerning cancer research. Much of the work I share here has application to human cancer as well. Third, much of this research information is applicable to other cancers as well. This means that progress in the studies of other cancer types will be much more rapid. Lastly, as dog enthusiasts, understanding the genetics of cancer will allow us to develop tests and breeding programs to avoid those types of cancer which may have a hereditary aspect to them.
Jeff Vidt, DVM
(8/29/12)

Dr. Linda Tintle and Dr. Jeff Vidt maintain web sites full of information about the Chinese Shar-Pei. They can be found at www.wvc.vetsuite.com and www.drjwv.com. Dr. Vidt has a “Vets Only Section” of his web site. Vets can click on his link to find instructions on how to get into the area for vets only.

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Post-Mortem Examination in the Chinese Shar-Pei by Jeff Vidt, DVM

In veterinary medicine the death of an animal patient is often thought of as the end of a medical case. However until a thorough post-mortem examination is completed, the case is not closed. In fact, the post-mortem examination (autopsy, necropsy) is a very useful and necessary procedure in the diagnostic process as it often defines the cause of death.

Why do a post-mortem examination? A good post-mortem has five benefits:

  1. Benefit to the owner/breeder:
    • It may reveal deficiencies in husbandry practices which can be modified or corrected.
    • It may reveal hereditary and/or congenital (birth) defects which may influence future breeding decisions.
    • By pinpointing the underlying disease process or processes, it allows the initiation of treatment for similarly affected individuals in a litter, household, kennel, etc.
    • The results of a post-mortem exam may facilitate the development and implementation of a preventive medicine/ husbandry program in the kennel to avert future deaths if possible.
  2. Benefit to the attending veterinarian:
    • A specific diagnosis, in many cases, leads to a specific treatment.
    • It can reveal individual kennel problems and these can serve as a starting point when future disease problems occur. This avoids time consuming trial-anderror treatments and allows specific treatment and preventive measures to be started earlier.
    • It adds to the experience and learning of the veterinarian.
  3. Benefit to the breed:
    • It may reveal breed-specific problems.
    • It will provide useful information to other breeders and veterinarians.
    • It allows accumulation of specific information concerning the deaths of individuals in that breed and allows for statistical analysis and compliation of data.
  4. Benefit to humans:
    • Since animals live with and amongst humans it may reveal zoonotic diseases which may be transmitted to people. This allows public health personnel to be notified and act to prevent human exposure and disease.
    • We now know the close relationship genetically between animals and humans. More and more we are finding the same hereditary and genetic diseases in animals and people. The results of the post -mortem examine may facilitate the development of animal models for human disease which can lead to new treatments for both animals and people.
  5. The post-mortem examination often results in “closure” for the owner, the veterinarian and other people involved in the death of an animal.

What constitutes a thorough post-mortem examination? The post-mortem examination consists of the following categories:

  • Gross pathology
  • Histopathology
  • Toxicology
  • Microbiology
  • Parasitology
  • Virology
  • Clinical pathology

Gross Pathology

This consists of the examination of every organ and system, including the brain and spinal cord. By visual examination, the veterinarian is looking for obvious abnormalities in organ appearance and the relationship between organs. The body is examined for trauma due to vehicles, bite wounds, lacerations, wounds caused by projectiles, burns, chemicals, etc. Many bacterial and infections as well as cancer will often produce characteristic changes in organ appearance – these often determine the direction of the rest of the post-mortem exam. All too often the examination ends here. It must be pointed out that the gross appearance of an organ can be misleading and degenerative changes following death can be misinterpreted — it isn’t always like a CSI episode. That being said the gross exam is useful in revealing the following broad categories of problems such as neoplastic changes resulting in tumors, potential bacterial and viral diseases, foreign objects, trauma, congenital or hereditary defects.

Histopathology

This microscopic examination of tissues is very important and useful. Many disease problems and processes are not visible to the naked eye and not obvious on the gross exam. Tissue samples are harvested from suspicious areas as well as the liver, spleen, intestinal tract, kidneys, pancreas, lymph nodes and lung. Additional samples might include heart muscle, skeletal muscle, nervous system, the eye and bone. These samples are sent to a veterinary diagnostic laboratory and it may take up to several weeks for the results to be reported. Histopathology will often give the definitive diagnosis so it is a very important procedure to do. New procedures have entered the field with the advent of immunohistochemistry staining, Congo Red staining, etc.

Toxicology

Although not commonly done, the toxicological examination is done in those cases where poisoning, whether intentional or accidental, may be involved. In these cases blood, stomach/ intestinal contents and samples of the ingested material are sent to the laboratory for analysis.

Microbiology

Here samples are taken for bacterial culture. The causative organism is identified and tested against various antibiotics to determine its susceptibility. Most commonly the lungs, trachea, urinary tract and reproductive tract are cultured. Cultures can also be done on intestinal contents, any discharges or abscesses. Time is especially critical in this phase of the post-mortem exam – upon the death of the animal normal bacteria from the gut invade the tissues and will obscure the results.

Parasitology

This aspect of the post-mortem involves the examination of the lungs, intestinal tract and heart for evidence of internal parasites. Many parasites are only visible under the microscope and not all are picked up on routine fecal exams.

Virology

This phase of the post-mortem examination is perhaps the most difficult and costly. Viral isolation requires special laboratory equipment, special tissue culture media for growing viruses and time. Viral isolation can take 4 weeks or longer. Special transport media is necessary for shipment of samples, although many times a local human hospital can be helpful. Electron microscopy is also used to identify viruses which require special processing. Typical tissues cultured for virus isolation in clued the liver, kidney, lungs and intestines.

Clinical pathology

Included in this category is routine blood testing which can be hampered due to storage conditions of the body, time after death, and many other factors. Newer methodologies include DNA/RNA analysis, PCR techniques, serology, and other testing procedures.

Up to this point we have addressed what goes into a thorough post-mortem examination and why we perform one. I will also say that many veterinary hospitals and veterinarians are not equipped or have the time and staff to do a thorough post-mortem examination. Often the exam is shortened to a rapid dissection of the body with harvesting of samples from appropriate tissues. Now I’d like to address the breeder/owner’s responsibility:

  • Cost – as one can imagine, a good postmortem examination is a costly procedure. It takes time to do a thorough exam, laboratory costs are high and the techniques involved are complex. A rough estimate would be in the hundreds of dollars.
  • Time – the time to decide to do a post-mortem exam is before the animal dies. This allows the veterinarian to obtain fresh samples as soon as possible and optimizes the chances of getting useful results.
  • If an animal should die at home and a veterinarian is not available, don’t freeze the body. It is much better to refrigerate the body. This prevents freezing artifacts which confuse the pathologist examining the tissues.

The death of a pet is traumatic both for the owner and the veterinarian. Too often, the post-mortem examination is rushed at the last minute or, worse yet, forgotten. It is important to communicate your wishes to the veterinarian early so the necessary procedures can be scheduled rapidly, samples obtained quickly and the examination performed efficiently.

The Chinese Shar-Pei dog breed has a genetic predisposition to an autoinflammatory disorder known as Familial Shar-Pei (FSF). It is an heredofamilial episodic fever disorder characterized by a high temperature (typically greater than 105° F) lasting 12-36 hours, often with a swollen, painful hock joint (Swollen Hock Syndrome, SHS which can occur in 40% of the FSF dogs) and systemic reactive amyloidosis leading to kidney failure in about 15% of these dogs. There currently are no diagnostic blood or DNA tests available to screen for or diagnose this disorder. As part of the research into the genetics of FSF the Health Committee of the Chinese Shar-Pei Club of America, Inc. has asked owners whose dogs have died or were euthanized in kidney failure to have a necropsy done and to request Congo Red staining (CRS) of the tissues submitted. Congo Red staining is the “gold standard” for the presence of amyloid. Unfortunately, H & E staining of tissue specimens for the presence of amyloid is not as accurate or reliable as CRS. The Health Committee and the CSPCA, Inc. ask that any veterinarian and/or laboratory receiving a request from a Shar-Pei owner to have CRS done on submitted tissues to please comply with that request. If the laboratory is not equipped to do CRS please inform the owner so that other arrangements can be made. We hope the CRS results can be used by breeders to evaluate and modify their breeding programs until definitive blood screening procedures for FSF can be developed and made available to the fancy.

©Jeff Vidt, DVM Chairman, Health Committee, Chinese Shar-Pei Club of America, Inc.

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CRS Letter for Vet