Shar-pei fever is a disorder that resembles familial Mediterranean fever of humans. The initial stages of the disease are characterized by recurrent episodes of fever that last approximately 24 to 36 hours. The first episodes are typically seen in young adult dogs. Roughly half of the dogs also suffer swelling in and around joints, most commonly the hock, which is equivalent to the human ankle joint. Many dogs are lethargic secondary to the fever, and may have a reduced appetite. Even if joint swelling is not seen, dogs may be stiff or lame, and may be reluctant to move. Less commonly, they may have swelling and pain associated with the muzzle, or abdominal pain, vomiting and diarrhea.

The fevers are believed to be associated with an elevation of a cytokine called Interleukin-6 (IL-6). Interleukin is a substance produced by white blood cells and other cells in the body, which promotes an inflammatory response. Dysregulation of the immune system is thought to be the cause of the elevated IL-6 levels.

IL-6 production leads to production of inflammatory proteins, which in turn leads to production of an abnormal protein called amyloid. Amyloid accumulates in the body and is eventually deposited in multiple organs. The organs most commonly affected include the kidneys and liver. This in turn may result in kidney and liver failure.

Many dogs with a history of recurrent fevers develop kidney failure between the ages of 3 and 5 years. Clinical liver disease is less common, although it has been reported. Dogs in kidney failure may experience weight loss, vomiting, diarrhea, loss of appetite, increased thirst, and increased urination.

Other diseases may cause clinical signs similar to those seen with shar-pei fever. These include:

Systemic lupus erythematosus (SLE). This is an autoimmune, or immune-mediated disease in which the body attacks its own cells. Joint inflammation, lameness, kidney disease, and fever are common manifestations of SLE.

Immune-mediated polyarthritis. This is another immune-mediated disease, which is limited to joint inflammation. Dogs may have a fever but do not have involvement of other organs.

Septic arthritis. Infection of one or more joints could cause similar clinical signs. Most joint infections are limited to one joint, whereas shar-pei fever usually involves multiple joints.

Tick-borne disease. Infectious diseases spread by ticks may cause joint inflammation, lameness, fever, and even kidney disease, among other signs. These include Lyme disease, Ehrlichia and Rocky Mountain spotted fever.

Rheumatoid arthritis. This is an autoimmune disease that causes bony destruction of joints. The swelling associated with shar-pei fever does not cause bony lesions, but the clinical signs may be similar.

Severe bacterial infection. A bacterial infection such as pneumonia, endocarditis (infection of a heart valve), urinary tract infection, abscess, or other sites of infection in the body will commonly cause fever, pain, and reluctance to move. Secondary inflammation of the joints may also occur in some cases.

Neoplasia (cancer). Although less likely in dogs less than two years of age, cancer can cause fever and discomfort, mimicking the signs of shar-pei fever.