Familial Shar-Pei Fever and Familial Amyloidosis
of Chinese Shar-Pei Dogs
Linda J.M. Tintle, D.V.M.
Shar-Pei with Familial Shar-Pei Fever (FSF):
* Have one or more bouts of unexplained fever, usually 103-107 degrees F (39.4-41.7 degrees C) but rare cases may go higher.
* If they do not have a fever, it is NOT FSF. (Assuming not on colchicine).
* Fevers usually start before they are 18 months old but adult-onset attacks are not uncommon. Fever episodes usually become less frequent with age.
* Fever episodes last 24-36 hours in most cases without treatment.
* Of the dogs that experienced fevers, approximately 53% had experienced Swollen Hock Syndrome (SHS) at some time along with the fever.
* Be very careful not to mistake the normal "socks" (excess wrinkling around the hocks on some Shar-Pei) for SHS.
* One or more of the following signs may accompany fever episodes:
* Swelling around a joint (cellulitis) with or without inflammation of the joint itself. One or more joints may be affected but most cases involve the tibiotarsal or hock joint (SHS).
* Sometimes a swollen painful muzzle.
* Abdominal pain, reluctance to move, "roached" back, mild vomiting or diarrhea, shallow rapid breathing.
Familial Mediterranean Fever (FMF) vs. FSF - FMF is:
* An autosomally recessive inherited periodic fever disorder of humans. The hereditary fever syndromes are inherited disorders characterized by self-limited episodes of fever with inflammation of joint or body cavity linings without any apparent infectious cause.
* Characterized by recurrent bouts of fever, usually starting in childhood.
* Polyserositis (inflammation of the thin membranes that line certain cavities of the body... joints, abdomen, chest, etc.) resulting in abdominal, chest and joint pain, usually involving the knee or ankle.
* Swelling/inflammation of the skin about the ankles or top of the foot.
* Free from symptoms between attacks.
* May develop amyloidosis.
Shar-Pei with FSF have abnormally high resting levels of a cytokine called Interleukin-6 (IL-6).
* IL-6 turns on various parts of the immune system. It is involved in controlling the fever response and is a trigger, alone or with other cytokines, for the production of the acute phase reactant proteins (APP) of inflammation... the precursors of Amyloid AA. Chronically elevated levels of IL-6 and other cytokines lead to chronically elevated levels of the APP.
* The APP are normally produced during active inflammation. The healthy animal breaks down the APP soon after the injury or disease and the toxic wastes are excreted from the body.
* Amyloidosis occurs when the APP cannot be broken down normally by the animal because of a defect in metabolism or when a large amount of APP continuously overwhelms the body's ability to get rid of it. Amyloid is then deposited outside the cell walls and not eliminated from the body. The build-up of the waste product amyloid is what causes the disease. Amyloid may be detected in many different organs and in blood vessels. In the kidneys, the damage is irreversible and usually results in kidney failure and subsequent death of the dog.
FSF is an autoinflammatory disease characterized by dysregulation of the normal paths of inflammation.
Inheritance of FSF and Amyloidosis in Chinese Shar-Pei.
* Published research indicates that this trait is compatible with an autosomal recessive inheritance. (AL Rivas, L Tintle, JM Scarlett, CP van Tassel, & FW Quimby Journal of Heredity 1993; 84:438-442.)
* My personal opinion, based on my experience and pedigree analysis, is that heterozygous carriers may (or may not) experience fevers +/- SHS but do not die prematurely from amyloidosis. I believe the homozygous animals (which usually but not always experience fevers +/- FSF) are the ones dying prematurely from amyloidosis. There is evidence that environmental influences are also important in whether or not an at-risk individual develops amyloidosis.
* Private communication with many of the original breeders and importers of these dogs has led me to believe that many of these imported foundation dogs were affected by this immune system dysregulation. Since all lines go back to this same small genetic pool of dogs, it is not surprising that the problem is widespread throughout the breed and throughout the world.
- In people with "Phenotype II" FMF, signs of amyloidosis may precede outbreaks of fever or the patient may never experience or report any fever.
- Fever episodes should be considered to be an important marker that the dog is at extremely high risk to develop amyloidosis and should be carefully monitored BUT not all FSF patients will develop amyloidosis.
Amyloidosis>>> kidney failure or, less commonly, liver disease/ failure.
Amyloidosis is a killer.
* Deaths have been reported to me as young as 8 months of age and as old as 12 years of age. It most commonly strikes between 3 and 5 years of age.
* Amyloidosis can only be diagnosed by surgical biopsy or by tissues obtained at autopsy. The abnormal amyloid protein is identified with special stains when examined under the microscope.
Frequency of FSF.
* A survey done at the 1991 CSPCA National Specialty and data from records at my own and Dr. Jeff Vidt's practice suggests that the incidence of FSF in Shar-Pei is about 23-28% affected. I believe the incidence may be higher now.
How is FSF diagnosed?
* No single test is yet available
* Still a clinical diagnosis by history, signs and excluding the other possibilities.
* Blood tests are usually negative/normal except that an elevated white blood count with a left shift is not uncommon as is mildly elevated alkaline phosphatase levels.
I perform the following minimum database on patients with possible FSF and then at least annually thereafter:
* Complete blood count (CBC) with differential, serum chemistry panel, and complete urinalysis (UA) on a first morning urine sample.
I also routinely recommend these tests on all bitches prior to breeding and studs at least annually! There are few worse horrors for a breeder than having the stress of pregnancy cause a bitch to go into kidney failure and die before the pups are a few weeks old and then having to raise a litter of orphan puppies which you know are carrying the gene for amyloidosis.
* Lyme Disease (Borreliosis) and other tick borne diseases should be ruled out in endemic areas. Do not forget to consider Leptospirosis where endemic.
* If UA suggests an increased amount of protein is being lost in the urine, I recommend a urine protein to creatinine ratio be run on the urine. Most affected Shar-Pei have medullary amyloid and may or may not have proteinuria (unlike humans) but proteinuria is always a significant finding. Loss of ability to concentrate urine (specific gravity consistently 1.010 to 1.022) is a more common early indicator of a problem.
* Immune panels, joint taps, radiographs, cultures, immunoglobulin levels, and other diagnostic procedures are sometimes needed in individual cases.
Treatment of FSF episodes.
* Tender loving care, close observation of body temperature and otherwise benign neglect.
* Buffered aspirin, Metacam (metacarpfen) - Canadian S-P owners have reported that this has worked very well in reducing fever and I am starting to recommend having it on hand to my clients' whose dogs experience episodes of fever now that it is available in the U.S.
* 1.0 ml of 50% Dipyrone SQ, or Banamine (flunixin meglumine) to reduce fever and provide pain relief, particularly for fevers > 105 degrees.
* Extremely high fevers or other systemic inflammatory response syndrome (SIRS) may indicate that rapid aggressive iv fluid therapy and shock treatment is necessary in some very rare cases. FSF episodes can be fatal and should never be shrugged off as inconsequential.
* There is no infection and therefore, antibiotics are unnecessary unless the veterinarian is concerned that the stressed dog may be secondarily infected.
- Recently, a few cases of severe pustular dermatosis with high fevers and vast sloughing of skin have been reported to or seen by Dr Jeff Vidt and I. These seem to resemble the "flesh eating" Streptococcus infections reported in humans (although other bacteria have been cultured as well) and require aggressive antibiotic and supportive treatment. These can be fatal even with treatment. A recent reports suggest that this is an immune mediated vasculitis and steroids +/- azathioprine may be indicated.
Acute febrile neutrophilic vasculitis of the skin of young Shar-Pei dogs.
Aust Vet J 80:200-6 2002 Apr
Immune-mediated vasculitis in a shar-pei with swollen hock syndrome.
Can Vet J 42:137-9 2001 Feb
I have seen most of my cases of this start with a “routine” FSF episode which for some unknown reason triggers the immune mediated vasculitis and sloughing. Here is a photo of a very severe case that did survive despite lesions covering large portions of her body:
This is a very, very rare complication of an FSF episode.
* Used in humans for over 3000 years and most commonly used as a treatment for gout.
* Used in FMF patients to reduce the frequency and severity of painful fever episodes and prevent the development of amyloidosis.
* Before colchicine therapy, up to 30% of all FMF patients died prematurely (usually around age 40) of amyloidosis.
* I currently recommend the use of colchicine prophylactically in any Shar-Pei that I believe to have FSF as soon as I am convinced of my diagnosis. I do not recommend waiting until evidence of disease due to amyloidosis is seen. At that point, it is almost too late.
* We have had some Shar-Pei on colchicine for over 7 years and I have yet to see evidence of any serious side effects other than gastrointestinal disturbances (diarrhea +/- vomiting) which resolve when the drug is withdrawn. Some dogs are, however, unable to tolerate the drug because of associated diarrhea. Others seem to tolerate a reduced dosage.
* In FMF treatment, the drug has been shown to be safe in children as young as 3 years of age, in pregnant women, and when given lifelong. Fatalities associated with massive overdoses have been due to bone marrow suppression. I have monitored CBC's in my patients and have not seen evidence of bone marrow suppression but this should always be kept in mind.
* I recommend once daily treatment with 0.025-0.03mg/kg for 2 weeks and if no gastrointestinal problems have occurred, I double the dose to twice daily. For your average Shar-Pei, this is one 0.6 mg tablet twice daily. I will provide a lengthy treatment protocol with pertinent scientific references to any veterinarian upon request.
* I personally believe that this drug works in this disorder and is the best treatment option currently available. I would like to see double-blind controlled studies done to prove this but, so far no research has been conducted or funded.
- Dogs on colchicine may continue to experience some fever episodes. Some cease completely. Others commonly report a decrease in severity and frequency. Some owners report SHS without fever. I believe the colchicine works in dogs as it does in people: the control of fevers and the blocking of amyloid deposition are by two different pathways and on-going fevers are not evidence of worsening amyloidosis.
- There is no association between the number, frequency and severity of the episodes and the development or degree of amyloidosis. A dog that experiences one single fever episode in his entire life is just as likely to get amyloidosis as the dog that gets them every 7-10 days. Any fever episode typical of FSF should be considered a marker that the patient is at high risk for amyloidosis. This is also why I do not recommend waiting to see if they ever get another episode before starting colchicine!
Most Common Signs of Advanced Amyloidosis.
* Unexplained weight loss.
* Increased thirst and frequency of urination.
* "Bad Breath" as a result of uremia (the buildup of toxins/wastes in the bloodstream as the kidney +/- liver fails to process them).
How is Amyloidosis Treated?
* Slow the progression of irreversible kidney disease with dietary management and supportive care... prescription kidney diets, omega 3 fatty acids, low dose aspirin therapy, ACE-inhibitors (benazepril or enalapril), and antioxidants may be indicated in individual cases.
* Thromboembolism "throwing a clot" is not uncommon in these patients and is why low dose (1/4 of a baby aspirin once daily) may be recommended.
* Liver disease often shows up as severe jaundice along with weight loss, vomiting and inappetance. These cases seem to have a better prognosis than those primarily affecting the kidneys and have shown good response to colchicine therapy with survival times over 4 years possible.
Other causes of kidney failure in Shar-Pei (or... Why you need to get the biopsy/necropsy specimens).
* Renal Infarcts
You cannot assume that every Shar-Pei that died of kidney failure had amyloidosis. It is, however, the overwhelming cause of premature death in the breed.
Linda J.M. Tintle, D.V.M.
Wurtsboro Veterinary Clinic, P.C.
163 Sullivan Street
P.O. Box 910
Wurtsboro, New York 12790
Familial Shar-Pei Fever
Hyaluronanosis, Familial Shar-Pei Fever and Amyloidosis
Linda J.M. Tintle DVM
Familial Shar-Pei Fever (FSF) is a periodic fever syndrome that is characterized by random inflammatory events with high fever, sometimes with swelling about joint/s or muzzle, that usually last 12-36 hrs. FSF is an autoinflammatory syndrome (not autoimmune).
Hyaluronanosis: Shar-Pei over-express Hyaluronan Synthase 2 (HAS2) and excess hyaluronan (HA) leads to their unique skin thickening and wrinkles because of a regulatory mutation. The mutation is a duplication that occurs in multiple copies. Individual Shar-Pei dogs vary in the number of copies of this mutation from dog to dog. The mutation is a copy number variant or “CNV”.
Excess cutaneous mucin may form vesicles or bubbles in the fragile skin. Hyaluronan health is integral to Shar-Pei health. Damaged or degraded low molecular weight hyaluronan is a “damage associated molecular pattern” (DAMP) that can activate the innate immune system. Native high molecular weight HA is health promoting and healing. You may improve Shar-Pei health by preventing or offsetting damage to their abundant HA.
Their underlying genetic defect is an unstable duplication in a regulatory gene upstream of Hyaluronan Synthase 2 (HAS2) that is described as the “meatmouth” mutation in our March 2011 article published in PLoS Genetics. Original, traditional-type Shar-Pei with less padded muzzles, less skin thickening and wrinkling have a slightly different mutation in this same location. The “meathmouth” mutation appears to predispose Shar-Pei (and some Shar-Pei mixed breeds) to inappropriate inflammatory responses. This may result in chronic elevations of inflammatory chemical messengers in the bloodstream. Shar-Pei may have abnormal initiation and also amplification of inflammation as a result of this genetic copy number variant (CNV) mutation. They may over-react to infection and damage. The greater the number of copies of the mutation present in the dog, the more reactive inflammation may result when HAS2 is up-regulated. Hyaluronan is also degraded and turned over rapidly: in hours, days, or weeks depending on its location. The breakdown of HA into fragments for elimination may also contribute to autoinflammation.
Low molecular weight fragments of hyaluronan both activate and prime the inflammasome leading to the release of IL-1beta and then IL-6, two major drivers of fever and inflammation. Mutations leading to aberrant inflammasome function have been associated with the human autoinflammatory syndromes Familial Mediterranean Fever (FMF), TRAPS, CAPS and gout.
Shar-Pei with Familial Shar-Pei Fever (FSF) may show the following signs:
- * Have one or more bouts of unexplained fever, usually 103-107 degrees F (39.4-41.7 degrees C) but rare cases may go higher. Fever greater than 106 degrees is a medical emergency and owners should seek veterinary treatment for the hyperthermia.
- Without fever, it is NOT “classic” FSF. (Assuming not on colchicine & supplements).
- * Fevers usually start before they are 18 months old but adult-onset attacks are not uncommon. Fever episodes usually become less frequent with age.
One or more of the following signs may accompany fever episodes:
- * Swelling around a joint (cellulitis) with or without inflammation of the joint itself. One or more joints may be affected but most cases involve the tibiotarsal or hock joint (swollen hock syndrome). Of the dogs that had experienced periodic fever episodes, approximately 53% had experienced swollen hock/s at some time along with the fever when owners at the CSPCA National Specialty were surveyed in 1994. Be careful not to mistake the normal "socks" (excess wrinkling around the hocks) on some individual Shar-Pei for the acute swelling that occurs surrounding the hock during or around the time of a fever episode.
- * Sometimes a swollen painful muzzle.
- * Abdominal pain, reluctance to move, "roached" back, mild vomiting or diarrhea, shallow rapid breathing. The proinflammatory cascade give the dogs flu-like symptoms and similar discomfort.
Amyloidosis is a disease caused by abnormal deposition of the breakdown products of chronic inflammation in the extracellular matrix (between cells). The severity of disease and risk for amyloidosis will vary with the amount of inflammation initiated and the autoinflammatory over-reaction. The chronic background inflammation puts affected dogs at risk for developing reactive systemic amyloidosis which can lead to early death from kidney failure.
Not every dog with FSF will develop amyloidosis but the fevers are a warning sign that they have aberrant autoinflammation and are at high risk for kidney disease. Shar-Pei with FSF can live to over 10 yrs of age. Two of my mother’s Shar-Pei lived to 12 ½ and 15 ½ years respectively with lifelong FSF and this is not uncommon in my patients. By doing everything you can to reduce their chronic inflammation and monitor their disease, you can help them live their best possible lives - however long that may be. Unfortunately, a combination of genetic predisposition (increased CNV) and environmental influences may lead to early death from kidney or, more rarely, liver failure due to amyloidosis in some individuals.
The diagnosis of Shar-Pei Fever is made after ruling out other causes of fever with diagnostic tests indicated by the dog’s condition but a minimum baseline of first morning urinalysis, CBC, chemistry profile, T4, +/- panel for tick-borne diseases is common. Other tests, including those for autoimmune disorders, may be needed. It is a diagnosis by exclusion at this time. I am collaborating with Dr. Kerstin Lindblad-Toh and Mia Olsson on a genetic test using the CNV mutation that is currently in development and undergoing validation studies at the Broad Institute of MIT and Harvard and Uppsala University in Sweden. A commercial test that is accurate, meaningful and useful to veterinarians, Shar-Pei owners, and breeders is the goal of the on-going study.
Because fever events are a marker for the presence of autoinflammatory disease, therapy should be started early to prevent complications. Some dogs have only one observed fever event yet die prematurely from amyloidosis – the number and frequency of fever events does not correlate with the severity of underlying chronic inflammation. In rare instances, dogs may die of amyloidosis without any observed fever events or may have their first fever after going into kidney failure.
My current treatment recommendations for Shar-Pei Fever include 0.025-0.03 mg/kg of colchicine twice daily or less to bowel tolerance. I recommend that the dog be started on a low dose once daily and then gradually increased to the maximum recommended amount (up to the calculated dose above) as tolerated without diarrhea once or twice daily. For most average weight Shar-Pei, this is one 0.6 mg tablet given twice daily. Colchicine is a potent drug but it accumulates in white blood cells (the desired target for treatment) and GI signs occur long before other serious side-effects.
I have never seen evidence of any damage from colchicine except for a transient, treatable diarrhea that goes away when the drug is withdrawn in sensitive patients. Colchicine treats the underlying pathology by blocking the movement of neutrophils (one of the white blood cells), decreasing levels of cytokines (the messengers of inflammation) and blocking the formation of amyloid protein (a waste by-product of inflammation). In humans, it has proven to be safe in infants, pregnant women and when given lifelong. Treatment is for life. I have been using the drug since 1993 and have had individual patients on the drug safely for over 10 yrs. Some dogs cannot tolerate colchicine without chronic diarrhea and they are given smaller amounts or none if it is severe. Colchicine and cyclosporine (Atopica®) should not be given together because of increased risk of bone marrow suppression.
Currently, sale of colchicine has been restricted by the FDA to one manufacturer, URL Pharma, under the brand name "Colcrys®" with an exorbitant price increase. URL Pharma is instituting a Patient Assistance Program for Shar-Pei that is to be administered by NeedyMeds. There is an application for the program (income adjusted fee structure) but the application is not yet on www.NeedyMeds.org website as of April 4, 2011. The application may be obtained by calling 888-811-8423 at this time. Applicants must provide a valid Colcrys prescription from a licensed veterinarian, and must attest that Colcrys will be used solely for their Shar-Pei dog. Applicants who qualify for the program will be able to select a 30-day supply (60 tablets), 60-day supply (120 tablets) or 90-day supply (180 tablets) of Colcrys. Those receiving financial assistance must re-apply for the program annually. The prescribing veterinarian must complete and sign several portions of the application. Colchicine may also be prescribed and purchased legally through compounding pharmacists in tablets or flavored suspension.
I treat the fever events with 50% dipyrone (500mg/ml) injectable (usually 0.5-1.0 ml/dog under the skin), or meloxicam (Metacam®), a non-steroidal anti-inflammatory drug or NSAID (by weight per package insert instructions). Dipyrone is an IL-1 beta inhibitor that is available from compounding pharmacists as injectable or in oral suspension or may be purchased over-the-counter in many non-U.S. countries. Aspirin has also been reported to be effective. Some fevers are very serious and can require emergency veterinary treatment if they approach or exceed 106 degrees F (41° C). Shar-Pei owners should discuss treatment of acute fever events with their veterinarian because treating the fever as early as possible in the inflammatory cascade can often stop it from becoming life-threatening and it is best to have medication available on-hand at home. Avoid giving NSAIDs with corticosteroids like prednisone and your veterinarian should be alerted your dog is vomiting because gastric ulcers can be a common complication.
Use caution with ice packs or baths: external cooling efforts should be reserved only for those dogs with fevers approaching 106 degrees while en route to a veterinarian. Unless the dog’s internal thermostat is reset with medication, the dog’s body will simply work harder to keep the fever up and may prolong the fever event. An ice pack wrapped in a damp towel that is placed in the groin area will help cool the patient en route to emergency care.
Some fever events may be initiated by infection. If the fever is severe, persistent and/or poorly responsive to anti-fever drugs like dipyrone, aspirin or NSAIDs, there may be an underlying infection that needs treatment. Veterinary care should be sought whenever the fever is severe, worse than usual for that dog, lasts longer than 48 hrs or is not responding to anti-inflammatory medication. In rare instances, a neutrophilic vasculitis and/or septic shock-like syndrome (STSS) with skin sloughing can occur. The latter is often associated with bacterial hyaluronidases that break down the abundant mucin in Shar-Pei skin.
Your Shar-Pei should get regular and routine monitoring of first morning urine with urinalysis (UA) as well as a CBC, blood chemistry profile and T4. Urine Specific Gravity at or below 1.020 is often the first sign of Shar-Pei kidney trouble and, if present, the UA should be repeated to see if the dog has a consistently low specific gravity. Medullary amyloidosis is the most common kidney disorder in Shar-Pei and proteinuria is usually a late-stage event. Urine protein levels should also be monitored and a urine protein to creatinine ratio performed if proteinuria is found on routine UA. FSF patients should be examined and tests performed whenever they are not eating normally, if they are vomiting, having diarrhea for more than a few days, acting sick in any way or if they are just “not right”. The bare minimum is annually in the healthy active young dog and many dogs should be checked more often.
In addition, Shar-Pei are prone to mast cell disease including mast cell tumors. The binding of HA to its receptor CD44 has been shown to play a critical role in regulation of murine cutaneous and connective tissue mast cell proliferation. It appears that CD44-HA regulates resident cutaneous mast cell populations. As the CD44-HA interaction may modulate local immune responses through regulation of mast cell functions, excessive HA and its subsequent damage and degradation may also play a role in the breed’s predilection for allergic skin disease and other mast cell driven inflammation.
Corticosteroids (for example medications like prednisone or dexamethasone) or cortisol produced by the dog’s body during stress (this may happen during a high fever or when ill) can shut down the production of hyaluronan by HAS2. These steroids may shrink the Shar-Pei’s muzzle and they may lose wrinkles. Very low dose prednisone is sometimes used for this reason to treat severe vesicular cutaneous mucinosis (bubbles of mucin in skin) or lymphedema of the hocks (chronic swelling due to fluid buildup). A Shar-Pei that has a suddenly shrunken muzzle for no apparent reason should get a full physical exam and lab tests.
Addressing Hyaluronosis (the downside to Shar-Pei Wrinkles):
1. Feed a High Quality diet low in simple carbohydrates: grain-free or containing small amounts of whole healthy fresh grains if possible. Pasture-fed meat source is preferable if money is no object (grain-fed meat has a high ratio of omega 6 to omega 3 fats and is lower in antioxidants and conjugated linoleic acid). The goal is to shift the arachidonic acid pathway away from pro-inflammatory end-products. A high dietary omega 3 to omega 6 fatty acid ratio may help reduce inflammation and result in improved overall health (including decreased anxiety!).
2. High dose omega 3 fatty acids from fish oil daily. Again, shift to anti-inflammatory end-products but also for its resolvins and other inflammation-resolving mechanisms at high doses. A high dietary omega 3 to omega 6 fatty acid ratio may help reduce inflammation and result in improved overall health including decreased anxiety. (900-1800mg EPA, 450-900mg DHA/day – source is important to ensure no rancidity or contaminants).
3. Lecithin: 1-2 Tbl of granules (7.5 – 15 gms) per day in food. To alter the choline composition of the “hyaluronasome” in plasma membrane lipid rafts; may impact how HA fragments are internalized for further degradation.
4.HyVitality™: a formulation of my recommended vitamins, minerals, antioxidants and phytochemicals that were chosen for their HA health promoting effects. Magnesium is integral to stabilizing HA in its high molecular form and magnesium deficiency is a very common finding in the breed. Severe cobalamin (Vitamin B12) deficiency is also common in Shar-Pei. This supplement was developed because it was difficult for clients to purchase the correct canine dosages using over-the-counter products designed for humans. Working with a trusted manufacturer has allowed me to be assured of purity and quality: Made in U.S.A. in a cGMP facility. (Average Shar-Pei dose contains 50-80mg Alpha Lipoic Acid, 60mg Coenzyme Q10, 100-200mg Magnesium citrate, 1000 mcg Methylcobalamin, 25mcg Vitamin K2 and a proprietary blend of Boswellia Serrata, Curcumin, Diosvein™ Diosmin & Biotivia™ Trans-Resveratrol). HyVitality is dosed by weight. More information at www.hyvitality.com.
5. Vitamin C, 500mg. Shar-Pei with excess HA may need more antioxidants like Vitamin C. Also, I suspect that Shar-Pei may not synthesize adequate Vitamin C because Vitamin C and HA compete for similar biochemical synthetic pathways (both are formed by glucuronidation).
6. Ensure Adequate Vitamin D3. Active Vitamin D modulates the over-active toll like receptors (TLRs) in inflammatory disease, returning them to a more normal functionality. HA fragments bind to TLRs to activate the pro-inflammatory cascade. Shar-Pei on home-cooked diets or who are fed commercial diets and supplemented more than 10% of their calories with "extras" or who have active inflammation may have additional or increased need for Vitamin D3. Need for Vitamin D3 in dogs has been estimated to be 50-475 IU per 10 lbs of body weight per day. Most dogs on commercial diets get at least this in their diets but more may be needed if a dog is not on a balanced commercial dog food, has severe allergies, arthritis or chronic inflammation. Discuss baseline testing with your veterinarian if you are concerned that your dog may need supplementation.
7. Thyroid Function: Treat any signs of secondary hypothyroidism with thyroid supplementation. Common signs include very sparse or missing coat, particularly along the back and inside of the thighs and hindquarters, with a generally brittle, lighter coat on the torso. HA fragments may down-regulate TSH releasing hormone via TLR2 binding, leading to clinical hypothyroidism characterized by low or low normal TSH and very low to low normal T3/T4 and I am looking this in Shar-Pei now. Response to therapy will be softer, thicker, and richer colored fur with hair re-growth, especially on hindquarters, and improved overall health and activity if the dog is functionally hypothyroid. Your veterinarian will monitor therapy to keep T4 below 4 µg/dL.
8. Probiotics and attention to bowel health. Skin and bowel are the immune system's biggest barriers and they are both HA rich areas. Inflammatory bowel diseases including colitis are very common in the breed. Some cases of FSF flare-ups and increased frequency of fever events have responded to treatment directed to eliminating over-growth of pathogenic GI bacteria in IBD patients or stress colitis. (If diarrhea is frequent or persistent, discuss diagnosis and possible treatment with prescription drugs with your veterinarian.)
9. Fanatical attention to skin and ear issues. Bathing by shampoo or washcloth wipe-downs as needed (microfiber dust cloths work well) - up to daily when skin is inflamed and at least every 2 weeks in a "healthy" Shar-Pei. Remove superficial yeast, bacteria (potential sources of hyaluronidases, enzymes that damage HA) and allergens like pollens, molds, dust that may activated mast cells. At least weekly ear cleaning/flush unless the Shar-Pei has a large, open, healthy ear canal.
10. Low dose 81 mg aspirin: ¼ - ½ tablet per day in dogs with no signs of gastric upset. Platelet derived growth factor might be an important mediator in their disease and aspirin also decreases risk of thromboembolic events. Be cautious as the breed has an increased risk for GI ulceration.
11. Detect problems early: Your veterinarian should see your Shar-Pei regularly for a complete physical examination and regular, routine monitoring of first morning urine with urinalysis (UA) as well as a CBC, blood chemistry profile and T4.
Eliminating inflammatory triggers, supporting healthy hyaluronan, reducing silent chronic inflammation wherever possible, providing good nourishment and playful daily exercise are key to Shar-Pei health.
More Information from Dr. Tintle
Listen to a podcast from AKC on Shar-Pei Fevers