Breed-Specific Amyloidosis: Familial Shar-Pei Fever

Jenessa A. Winston, DVM, North Carolina State University

ArticleLast Updated September 20137 min readPeer Reviewed
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  • In familial renal amyloidosis of shar-peis, deposition of amyloid can progressively disrupt normal renal architecture, leading to chronic kidney disease (CKD).

  • Amyloidosis is the extracellular deposition of fibrils formed by polymerization of proteins with a beta-pleated sheet conformation.

  • Reactive amyloidosis secondary to chronic infectious and noninfectious inflammatory disease and neoplasia is the most common form in animals.

  • Renal amyloidosis can result in CKD, proteinuria, and nephrotic syndrome.

  • Many shar-peis will have fever and swelling of the tibiotarsal joints (also called shar-pei fever or shar-pei swollen hock syndrome) before development of renal amyloidosis.

  • The cause of this syndrome in shar-peis is unknown.

  • Although this disease is considered genetic, not all shar-peis with the trait will develop renal amyloidosis (see Genetic Implications).

  • Not all shar-pei fever patients will have renal amyloidosis.


  • Renal dysfunction is the most common; however, other organ systems can be affected by amyloid deposition.

Genetic Implications

  • In shar-peis, this is an autosomal recessive trait.

Incidence & Prevalence

  •  Renal amyloidosis is estimated to occur in 23% of shar-peis in the United States.

  • True prevalence is unknown.


Breed Predilection

  • Shar-peis are predisposed.

  • Familial renal amyloidosis has also been reported in beagles, English foxhounds, collies, Walker foxhounds, and Abyssinian and Siamese cats.

Age & Range

  • Age of onset of clinical signs is typically 1–6 years (mean, 4.1 years).


  • More common in female than male dogs (female:male ratio, 2.5:1)


  • Amyloid A protein, formed by the polymerization of the amino acid terminal portion of serum amyloid A (SAA) in response to inflammatory cytokines, is the primary protein involved in reactive amyloidosis.

  • Affected shar-peis have increased serum concentrations of interleukin-6, a cytokine that stimulates synthesis of SAA and the release from hepatocytes.

  • Other cytokines (eg, tumor necrosis factor-α, interleukin-1β) are also involved.

  • These cytokines initiate the acute phase response characterized by fever, hepatic production of acute proteins (including SAA), and mobilization of neutrophils.

  • Amyloid deposition disrupts normal tissue architecture and can cause organ failure.

  • In shar-peis, amyloid deposition can occur in the kidneys, liver, spleen, pancreas, adrenal glands, thyroid glands, myocardium, prostate, lymph nodes, and GI tract. 

  • Most do not show signs of organ dysfunction other than kidney or hepatic disease.

  • Renal amyloidosis in other canine breeds can lead to marked proteinuria.

  • Only 25%–43% of affected shar-peis have proteinuria.1

  • Nephrotic syndrome—characterized by marked proteinuria, hypoalbuminemia, hypercholesterolemia, and edema—can be present.

  • Some affected dogs are at increased risk for thromboembolic disease, in part because of loss of antithrombin through the affected glomerulus.

  • A similar syndrome of fever and synovitis called familial Mediterranean fever occurs in humans.

History & Physical Examination

  • Intermittent episodes of fever ± joint swelling or pain

  • Episodes often precede amyloidosis, although these episodes may not be detected.

  • At initial presentation, intermittent high fever (ie, 103°F–107°F) and joint swelling (eg, tibiotarsal joints) that resolve ± treatment may be present.

  • Affected patients may appear normal if fever and joint swelling are not present.

  • Marked CKD may result in oral ulceration, uremic breath, and dehydration.

  • Nephrotic syndrome may result in ascites, SC edema, or both.

  • Acute onset of respiratory distress, tachypnea, or pelvic limb paresis may indicate thromboembolic disease.

  • Jaundice occurs if hepatic amyloidosis is present.

  • Hepatic amyloidosis has been reported in ~11% of cases.2

Clinical Signs

  • Signs include polydipsia, polyuria, anorexia, vomiting, dehydration, weight loss, weakness, and lethargy.



  • Renal biopsy specimen should be obtained from the renal cortex to reduce complications (eg, hemorrhage, infarction).

  • Because amyloid deposits are often limited to the medulla, the diagnosis may be unobtainable on renal biopsy; however, medulla biopsies are not recommended because of risk for complications.

  • Approximately 64% of shar-peis will have glomerular involvement.

  • Staining with Congo red (see Figure 1, Renal biopsy specimen stained with Congo red showing typical birefringence of glomerular amyloid deposits. Image courtesy S.P. DiBartola)

  • Light microscopy discloses amyloid deposits in various shades of red.

  • Polarizing microscopy discloses amyloid deposits in an apple green birefringence.

  • Amyloid deposition is confirmed by decolorization of Congo-red–stained deposits by potassium permanganate oxidation.

  • If intermittent fever and joint swelling precede onset of CKD signs in a shar-pei, renal biopsy is not recommended.

  • Treatment of presumed amyloidosis should be initiated.

  • Aspirates from other organs (ie, liver, spleen) can be obtained if positive staining with Congo red is documented.


  • Joint disease

  • Polyarthritis (ie, immune mediated, bacterial, viral, fungal)

  • Lyme disease, especially in endemic areas

  • Ehrlichiosis

  • Vaccine reaction

  • Renal amyloidosis

  • Other glomerular diseases

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Laboratory Findings

  • CBC

  • Nonregenerative, normocytic, normochromic anemia, secondary to CKD

  • Serum biochemistry profile

  • If renal amyloidosis is present:

  • Azotemia 

  • Hyperphosphatemia

  • Metabolic acidosis

  • Hypoalbuminemia

  • Hypercholesterolemia

  • Hyperglobulinemia

  • If hepatic amyloidosis is present:

  • Increased alkaline phosphatase, alanine transaminase, and aspartate transaminase activities

  • Hyperbilirubinemia

  • Urinalysis

  • Proteinuria is considered the hallmark of glomerular disease but is variable (25%–43%) in shar-pei fever because amyloid deposition occurs mainly in renal medulla.

  • Urine protein:creatinine (UP:C) should be measured if proteinuria is present.

  • UP:C >0.5 is considered abnormal. 

  • Isosthenuria

  • Systemic hypertension


  • Abdominal radiography can show hepatomegaly and relatively normal kidneys.

  • Abdominal ultrasonography can show hyperechoic renal cortex, decreased corticomedullary distinction, and a hypoechoic liver with rounded edges.

  • Other diagnostics:

  • Assessment of hypercoagulability

  • Coagulation panel

  • Antithrombin or antithrombin III concentrations

  • Thromboelastography

  • Postmortem findings

  • Confirmation of renal (or other) amyloidosis

  • Lugol’s iodine can be applied to the cut surface of the kidney, which will yield bluish-black dots within the tissue representing amyloid deposits.

  • Reactive amyloidosis can be confirmed by decolorization of Congo-red–stained amyloid deposits by potassium permanganate oxidation.



  • Initial treatments (see Table)

  • Supportive care as indicated (eg, NSAIDs) to reduce pain and fever and maintain hydration.

  • Colchicine

  • Colchicine can impair release of SAA from hepatocytes by binding to microtubules, which will prevent secretion; this may also prevent production of amyloid-enhancing factor.

  • Colchicine should be initiated after 2 episodes of fever and joint swelling and after other causes of polyarthritis have been excluded; this can prevent further amyloid deposition.

  • Colchicine will not eliminate amyloid that has already been deposited; if azotemia is present, colchicine may not reverse existing organ damage.

  • Therapy is lifelong, independent of persistent fever or swollen joints.

  • Adverse effects of colchicine include vomiting and diarrhea.

  • With long-term administration, bone marrow suppression and hypertension are noted.

  • Dimethyl sulfoxide (DMSO)

  • Treatment is controversial; there is no proven clinical benefit to date.

  • DMSO does not appear to solubilize amyloid fibrils; any benefit may be related to the antiinflammatory properties of DMSO.

  • Enalapril or benazepril

  • Angiotensin-converting enzyme (ACE) inhibitors for reducing proteinuria

  • Low-dose aspirin or clopidogrel

  • May decrease the frequency of thromboembolic disease

  • Should be started if serum albumin <2.5 g/dL

  • Aspirin should not be administered if the patient is receiving other NSAIDs.

  • Antihypertensive agents

  • Additional agents (eg, amlodipine) should be started if persistent hypertension is present (systolic blood pressure >170 mm Hg) after enalapril or benazepril initiation.


  • A diet formulated for dogs with renal disease is indicated.

  • Ensure adequate caloric intake.

  • Malnutrition is a major cause of morbidity and mortality in shar-peis with CKD.

  • Additional supplementation with omega-3 fatty acids may be beneficial.


  • Renal transplantation

  • Amyloid is likely to deposit in transplanted organs.


Patient Monitoring

  • UP:C, urinalysis, serum albumin concentration, serum creatinine concentration, and body weight should be monitored monthly when adjustments to therapeutic plan are made.

  • If a patient presents with fever only, consider monitoring with urinalysis and measuring serum creatinine concentrations q3mo.

  • Clients can monitor their dog’s body temperature to document febrile episodes.

  • Response to therapy

  • 50% reduction of proteinuria (based on UP:C) without increase in serum creatinine

  • Combination of 3–5 pooled urine samples for UP:C evaluation is ideal.

  • If systemic hypertension is present, blood pressure should be rechecked q3mo until stable.

  • More frequent monitoring is required if unregulated hypertension is present.

  • Once patient is stable, parameters can be monitored q3mo.

In General

Relative Cost

  • Shar-pei fever with renal amyloidosis may be costly because of lifelong medications, supportive care, hospitalization, and diagnostic monitoring: $$$$$

Cost Key



up to $100








More than $1000


  •  Poor to guarded

  • Optimal treatment is unclear, but early intervention with colchicine therapy may improve prognosis.

CKD = chronic kidney disease, SAA = serum amyloid A, UP:C = urine protein:creatinine

Editor’s note: This article was originally published in September 2013 as “Familial Shar-Pei Fever.”