Shar-Pei fever is a heritable syndrome of recurrent fever and inflammation affecting Chinese Shar-Peis. Affected dogs experience recurring episodes of high fever accompanied by arthritis, especially in the tibiotarsal joints. Shar-Pei fever is a diagnosis of exclusion. Colchicine has been recommended for the treatment of Shar-Pei fever; however, potential drug interactions must be considered.
Shar-Pei fever is a familial autoinflammatory syndrome of recurrent fever and nonerosive polyarthropathy, vesicular hyaluronosis of the skin and amyloidosis that affects Chinese Shar-Peis and crosses.
The Shar-Pei breed nearly went extinct in the 1950s. A small number of Shar-Peis were exported from Asia to the US in the 1970s. The offspring of these dogs are highly inbred because they have been heavily selected for a wrinkled skin phenotype.
Etiology of Shar-Pei Fever
An accumulation of excess hyaluronic acid in the upper dermis is the reason for the Shar-Pei's extremely wrinkled skin. A mutation of the hyaluronic acid synthase gene (HAS2) has resulted in its overexpression in dermal fibroblasts. In the US, ~23% of Shar-Peis are estimated to have this mutation and thus have large quantities of hyaluronic acid in their skin, resulting in extensive and thick skin folding. This hyaluronic acid can accumulate in cutaneous vesicles.
Hyaluronic acid also acts as an alarm that activates the innate immune system. It stimulates macrophages to produce excessive amounts of two cytokines: IL-1beta and IL-6. When they reach the circulation, these cytokines act on the brain to trigger a fever.
Dogs with highly folded skin are the most susceptible to developing fever syndromes. IL-1beta and IL-6 also act on hepatocytes to stimulate their production of acute phase proteins such as serum amyloid A (SAA). As a result, when hyaluronic acid escapes into their bloodstream, Shar-Peis develop episodes of fever and inflammation.
Clinical Findings of Shar-Pei Fever
Dogs with Shar-Pei fever experience episodes of high fever that last 12–48 hours and are accompanied by arthritis, especially in the tibiotarsal joints. These episodes may occur as often as every few weeks.
SAA concentrations remain high between episodes of Shar-Pei fever, so SAA is deposited in tissues to form insoluble amyloid. Amyloid, in turn, is deposited in organs such as the kidneys, liver, spleen, GI tract, and myocardium. These amyloid deposits can result in kidney or liver failure, leading to early death.
Diagnosis of Shar-Pei Fever
Diagnosis of Shar-Pei fever is based on the presence of compatible clinical signs in a Shar-Pei or cross. Other causes of fever must be ruled out.
The presence of amyloid deposits can be detected in renal biopsy by staining with Congo red. The detection of these deposits is required for a definitive diagnosis of Shar-Pei fever.
A genetic test is available to identify dogs at risk for Shar-Pei fever.
Routine screening for urinary protein loss is recommended in all Shar-Peis because it may result from renal amyloidosis, an important consequence of Shar-Pei fever.
Treatment of Shar-Pei Fever
The administration of colchicine (0.025 mg/kg, PO, every 48 hours for 1 week, then every 24 hours longterm) has been recommended for the treatment of Shar-Pei fever. Although the mechanism of action for this drug has not been determined, colchicine has anti-inflammatory effects, reduces neutrophil chemotaxis, and is considered the treatment of choice for Shar-Pei fever. Azole antifungals, macrolide antimicrobials, calcium channel blockers, and P-glycoprotein pump inhibitors increase blood concentrations of colchicine, potentially causing multiorgan failure due to colchicine toxicosis. Therefore, drug interactions should be considered before any drugs are added to colchicine treatment.
Maintaining good general health is also important in treating Shar-Pei fever. Vitamin supplementation has also been recommended (1).
Corticosteroids can be used to treat severe vesicular cutaneous hyaluronosis or lymphedema.
Key Points
Affected dogs experience recurring episodes of high fever accompanied by arthritis.
Shar-Pei fever is a diagnosis of exclusion; a genetic test is available for screening.
Treatment with colchicine should be started early; potential drug interactions must be considered.
For More Information
Dr. Linda Tintle (dedicated to the health of Chinese Shar-Pei)
Cornell University, College of Veterinary Medicine, Animal Health Diagnostic Center: Shar-Pei Autoinflammatory Disease (SPAID)
References
Tintle LJM. Hyaluronosis, Shar-Pei autoinflammatory disease (SPAID), familial Shar-Pei fever and amyloidosis. Unpublished paper; May 2016.
