Familial Shar-Pei Fever Linda J.M. Tintle DVM
Familial Shar-Pei Fever (FSF) is an autoinflammatory syndrome (not autoimmune). The underlying genetic defect is most likely a disruption in how the messengers of inflammation are controlled which causes chronic elevations of these mediators in the bloodstream. It is a periodic fever syndrome that is characterized by random inflammatory events with fever, sometimes with joint swelling, that usually last 24-36 hrs. It appears that the complex disorder involves multiple interactive genetic mutations, including one that has been found at a previously identified site in the genome associated with one of the human periodic fever autoinflammatory disorders. Shar-Pei may have abnormal initiation (fever disorder) and also amplification (other mutation/s) of inflammation. The severity of their disease and risk for amyloidosis will vary with the amount of inflammation initiated and their autoinflammatory over-reaction.
The chronic background inflammation puts them 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 big red flag that they have one of the defects leading to aberrant auto-inflammation 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. 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.
Your veterinarian will usually make this diagnosis after ruling out other causes of fever with diagnostic tests as indicated by your dog’s condition but a baseline of urinalysis on a first morning urine sample, CBC, blood chemistry profile, T4 +/- a panel for tick-borne diseases is most common. Other tests, including those for autoimmune disorders, may be needed. It is a diagnosis by exclusion now but scientists are working on developing DNA and other tests for the genetic mutations that put them at risk.
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.
My current recommended treatment of Shar-Pei Fever includes 0.025-0.03 mg/kg of colchicine twice daily. I recommend that the dog start on a low dose and try to gradually increase to the maximum recommended amount or the most of that that they can tolerate without gastrointestinal (GI) upset (usually diarrhea) twice daily. For most average weight Shar-Pei, this is one X 0.6 mg tablet 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 appear. 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 small amounts or none if it is severe. Colchicine and cyclosporine (Atopica) should not be given together because of increased risk of bone marrow suppression.
I treat the fever events with 50% dipyrone injectable (usually 1.0 ml/dog under the skin) (an IL-1 beta blocker) or Metacam (meloxicam, a non-steroidal anti-inflammatory drug or NSAID) by weight per package insert instructions. Some fevers are very serious and can require emergency veterinary treatment if they approach or exceed 106 degrees F (41 degrees C). You will need to discuss treatment with your 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. Do not give NSAIDs with corticosteroids like prednisone and alert your veterinarian if your dog is vomiting.
I would also recommend adding some or all of the following antioxidants and other supplements to your dog’s diet to offset the chronic inflammation that is the silent killer and because r ancid fatty acids and oxidized cholesterol in cell membranes have been linked to chronic inflammation and the deposition of reactive amyloid in current research: 50-100 mg alpha-lipoic acid once daily (do not exceed 100mg/day), a good quality human multi-vitamin (with A, D, E and complete B-complex vitamins), at least 2000 mg omega-3 fish oil (can be given 1-2 capsules twice daily of the over-the-counter fish oil capsules – I use a product that supplies a highly concentrated amount of pharmacologic grade fish oil in ½-1 tsp (1800mg EPA, 900mg DHA/tsp) once daily, 100-500 mg curcumin with bioperine per day with meals, 100-300 mg Boswellia twice daily. Feed a good quality diet and avoid rancid polyunsaturated, hydrogenated or trans- fats. Colchicine can lower levels of vitamin B12 (cobalamin) in the body and some Shar-Pei are already deficient in vitamin B12 so B-complex supplementation is important. Vitamin B12 is important in the biochemical pathways of inflammation and may be depleted because of their chronic disease. Vitamin B12 deficiency can cause chronic diarrhea and low-grade anemia in some Shar-Pei and I now routinely supplement with 1000 mcg/day by mouth. Recent studies have shown that oral absorption in humans is as effective as injectable and I have seen improvement after oral therapy in dogs. MSM has been reported to decrease the severity of fevers anecdotally but should be supplemented with molybdenum if given at high doses (50-75 micrograms/day if dose of MSM > 1000 mg/day). 100-200 mg Resveratrol/day may decrease levels of IL-6 and dampen effects of cytokine cascade. (Resveratrol should not be given along with Quercetin as the latter blocks its effects). Vitamin K2 (menaquinone, MK7) may also suppress IL-6 production by fibroblasts. Production of mucin (hyaluranon or HA) requires magnesium and I often prescribe 200 mg of magnesium (not oxide) daily after finding hypomagnesemia to be a frequent abnormality in S-P chemistry profiles.
Your dog should get regular and routine monitoring of first morning urine with urinalysis as well as a CBC, blood chemistry profile and T4. Dilute urine is often the first sign of kidney trouble and, if present, the urinalysis 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 but urine protein levels should also be monitored and a urine protein to creatinine ratio performed if proteinuria is found. FSF patients should be examined and tests performed whenever they are not eating well or at all, if they are vomiting, having diarrhea for more than a few days or acting sick in any way – 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.
Treatment/supplements to consider:
Colchicine
Vitamin B12
High dose omega 3 fatty acids
Magnesium
Multi-vitamin and mineral supplement
Alpha-lipoic acid
Resveratrol
Curcumin
Boswellia
Vitamin K2 (menaquinone, MK7)
Oct 2009
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