Shar Pei fever: from hocks to kidneys
Introduction
Shar Pei fever was first recognised over 30 years, but the entity’s aetiopathogenesis has not yet been fully elucidated.1 It is evidently a hereditary disease that follows an autosomal recessive model.
It has been estimated that the condition may affect as many as 23% of all Shar Peis in the United States.2 Despite the disease’s name and the fact it courses with recurrent episodes of fever, it has recently been proposed that fever is only one of a set of clinical signs that form part of a syndrome now known as Shar Pei autoinflammatory disease and which can lead to arthritis, dermatitis, otitis and systemic amyloidosis.3
Aetiopathogenesis of Shar Pei fever
Hereditary periodic fever syndromes are characterised by episodes of recurrent fever and inflammation with no known pathogenic mechanism or autoimmune cause.
A mutation has been found in Shar Peis that provides a link between episodes of recurrent fever and the selection of the “wrinkled” phenotype in this breed. The distinctive “wrinkles” seen in this breed are the result of an excessive accumulation of hyaluronic acid (HA) in the skin.4 HA can act as a proinflammatory molecule and trigger for the process.4
Clinical picture
The disease is characterised by short periods (12–48 hours) of recurrent episodes of fever (usually in young animals), accompanied by joint inflammation, above all in the tibiotarsal joint (which is why it used to be known as swollen hock syndrome).1,4
Dogs with Shai Pei fever have a greater chance of developing reactive systemic amyloidosis, which mainly affects the kidneys, although amyloid deposits can also be found in the liver, spleen, pancreas, adrenal glands, thyroid, prostate, myocardium, lymph nodes and gastrointestinal tract.2 As such, the signs of amyloidosis depend on the organ affected. In the case of renal amyloidosis, the most frequent signs are anorexia, lethargy, weight loss, polyuria/polydipsia, vomiting and occasionally diarrhoea.2,5 Although animals with renal amyloidosis may be brought in for consultation with a nephrotic syndrome, this does not appear to occur in Shar Peis.2
Diagnosis
A presumptive diagnosis can be made based on the presence of recurrent fever without a justified cause in a Shar Pei dog. Regarding the diagnosis of amyloidosis, clinical suspicion should be aroused by the presence of severe pathological renal proteinuria (quantified by calculating the urine protein/creatinine ratio), although the definitive diagnosis requires a renal biopsy.5
Unfortunately, in contrast to what normally occurs in other breeds, in Shar Peis, the amyloid material mainly tends to deposit in the renal medulla (where there are no glomeruli) rather than the cortex. This explains why Shar Peis have less marked proteinuria (and some dogs are even nonproteinuric) than other breeds with strictly glomerular amyloidosis.2 This means it is sometimes hard to diagnose amyloidosis in vivo, because renal medulla biopsies are discouraged due to the risk of severe bleeding.6 In any event, biopsies of the renal cortex have proven useful in the diagnosis of renal amyloidosis in the Shar Pei.2
The diagnostic study of these patients may reveal systemic hypertension, moderate to severe anaemia, hypoalbuminaemia, azotaemia and hyperphosphataemia, as well as isosthenuria and a tendency to hypercoagulability.2,7 All of these are a consequence of the disease’s progression towards end-stage chronic kidney disease. Therefore, the presence and severity of these alterations will depend on the moment of diagnosis.
Treatment
- Episodes of fever are usually treated with nonsteroidal anti-inflammatory drugs,1 and very rapid responses to metamizole have also been reported.4
- With respect to the management of amyloidosis, initiate one line of treatment to control the proteinuria and any other alterations associated with the kidney damage, and another aimed at reducing the severity of amyloid deposition.
- Antiproteinuric therapy is based on the administration of angiotensin-II converting enzyme inhibitors or angiotensin-II type 1 receptor antagonists, a renal diet, and acetylsalicylic acid or clopidogrel in an effort to prevent the development of thromboembolism.7
- Colchicine (0.025–0.03 mg/kg/12 hours, maximum dose 0.6 mg) or dimethylsulfoxide (90 mg/kg, orally 3 times a week or subcutaneously diluted ¼ in saline solution) are recommended to control amyloid deposition.
- Colchicine may be more effective in the early stages of the disease. Gastrointestinal side effects are typically associated with its use.
- Dimethylsulfoxide, on the other hand, may cause nausea, a garlicy odour and clouding of the crystalline lens (in chronic use). Intravenous administration is not recommended because it can cause haemoglobinuria due to haemolysis, perivascular inflammation and thrombosis.
In any case, the long-term benefits of these treatments need to be clarified.1,5,6 Other drugs tested in human patients but scarcely investigated in veterinary medicine include: IL-1 receptor antagonists, TNF-alpha inhibitors, eprodisate, and chlorambucil.5 The prognosis for Shar Pei fever once patients have developed signs of kidney disease is generally quite poor.2
Conclusions
Recurrent episodes of fever in Shar Pei dogs should raise the clinical suspicion of Shar Pei autoinflammatory disease. A more complete diagnostic study to confirm the presence of renal amyloidosis can be useful in these patients. With an early diagnosis, treatment can help slow disease progression.
