ISSN 2398-2969      

Shar Pei fever and Shar Pei autoinflammatory disease

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Synonym(s): Shar Pei hock, Familial Shar-Pei Fever, Swollen Hock Syndrome, Familial amyloidosis, Shar-Pei Autoinflammatory Disease (SPAID)


Introduction

  • Cause: impaired regulation of hyaluronan (HA) synthesis due to a genetic mutation leads to excessive HA concentrations provoking autoinflammation.
  • Associated with breed-specific mutation responsible for thickened wrinkled skin (hyaluronosis).
  • Presents with episodic fever that typically first occurrs before 18 months of age.
  • Autoinflammatory disorder that encompasses episodic fever, arthritis, recurrent otitis, hereditary cutaneous hyaluronosis, and systemic amyloidosis.
  • Fever events may be accompanied by periarticular joint swelling +/- associated sterile neutrophilic non-erosive intra-articular inflammation, usually affecting the tibiotarsal joint. Occasionally swollen, painful muzzle.
  • Diagnosis: breed, rule out other causes of fever of unknown origin. Genetic test.
  • Treatment: supportive, prophylactic.
  • Prognosis: guarded due to risk for amyloidosis.
Print off the owner factsheet Shar Pei fever to give to your client.

Pathogenesis

Etiology

  • Selection by breeders for increased wrinkling and skin thickness may have inadvertently selected for the CNV 16.1|5 meatmouth mutation, predisposing to autoinflammation.
  • Hyaluronan is a fundamental barrier molecule of the innate immune system and is a major component of the skin and gastrointestinal tract lining. Its function varies with its molecular weight. 
  • Shar-Pei have chronically increased levels of IL-6. Interleukin-6 is a trigger for APP production. Some, but not all, Shar-Pei may develop reactive systemic (AA) amyloidosis Amyloidosis as a result of chronic inflammation.
  • Hyaluronosis may be associated with increased presence of dermal mast cells.

Pathophysiology

  • Breed selection has targeted a thickened, wrinkled skin and a meatmouth padded muzzle appearance). 
  • This phenotype is a result of excessive hyaluronan deposition in the dermis.  
  • Hyaluronan plays a complex role in the body and when fragmented can act as a danger-associated molecular pattern (DAMP) activating pro-inflammatory cytokines (eg interleukin 1β and IL-6).  
  • Increased IL-6 provokes increased acute phase proteins (APP) Acute phase proteins
  • Reactive systemic amyloidosis may occur as a result of chronically increased (APP).  
  • Persistence of APPs (even between fever episodes) can precipitate amyloid deposition (predominantly in the kidney causing irreversible damage and progressive chronic renal insufficiency).

Timecourse

  • Recurrent bouts of fever, most commonly lasting 24-36 hours.
  • Death due to renal failure Kidney: chronic kidney disease (CKD) has been seen as early as 9 months of age but is most commonly seen between 2-5 and 8-10 years of age, with the presence of two groups hypothesized (but yet unproven) to be due to presence or absence of the modifier locus associated with amyloidosis.
  • Many dogs with recurrent fevers may live out lifespans greater than 10 years of age without succumbing to amyloidosis. The presence of fever is a marker, not a cause, of greater risk.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Olsson M et al (2016) Absolute quantification reveals the stable transmission of a high copy number variant linked to autoinflammatory disease. BMC Genomics 17, 299 PubMed.
  • Hayem G (2013) Chinese Shar-Pei dogs: A model for human Mediterranean fever? Joint Bone Spine 80 (4), 353-354 PubMed.
  • Olsson M, Tintle L, Kierczak M et al (2013) Thorough investigation of a canine autoinflammatory disease (AID) confirms one main risk locus and suggests a modifier locus for amyloidosis. PLOS One 8 (10), e75242 PubMed.
  • Segev G, Cowgill L D, Jessen S et al (2012) Renal amyloidosis in dogs: A retrospective study of 91 cases with comparison of the disease between Shar-Pei and non-Shar-Pei dogs. JVIM 26 (2), 259-268 PubMed.
  • Docampo M J, Zanna G, Fondevila D et al (2011) Increased HAS2-driven hyaluronic acid synthesis in shar-pei dogs with hereditary cutaneous hyaluronosis (mucinosis). Vet Dermatol 22 (6), 535-545 PubMed.
  • Doherty T A, Brydges S D, Hoffman H M (2011) Autoinflammation: translating mechanism to therapy. J Leukoc Biol 90 (1), 37-47 PubMed.
  • Olsson M, Meadows J R S, Truve K et al (2011) A novel unstable duplication upstream of HAS2 predisposes to a breed-defining skin phenotype and a periodic fever syndrome in Chinese Shar-Pei dogs. PLOS Genetics 7 (3), e1001332 PubMed.
  • Zanna G, Docampo M J, Fondevila D et al (2009) Hereditary cutaneous mucinosis in shar pei dogs is associated with increased hyaluronan synthase-2 mRNA transcription by cultured dermal fibroblasts. Vet Dermatol 20 (5-6), 377-382 PubMed.
  • Zanna G, Fondevila D, Bardagí M et al (2008) Cutaneous mucinosis in shar-pei dogs is due to hyaluronic acid deposition and is associated with high levels of hyaluronic acid in serum. Vet Dermatol 19 (5), 314-318 PubMed.
  • Flatland B, Moore R R, Wolf C M et al (2007) Liver aspirate from a Shar Pei dog. Vet Clin Pathol 36 (1), 105-108 PubMed.
  • Malik R, Foster S F, Martin P et al (2002) Acute febrile neutrophilic vasculitis of the skin of young Shar-Pei dogs. Aust Vet J 80 (4), 200-206 PubMed.
  • Tellier L A (2001) Immune-mediated vasculitis in a shar-pei with swollen hock syndrome. Can Vet J 42 (2), 137-139 PubMed.
  • López A, Spracklin D, McConkey S et al (1999) Cutaneous mucinosis and mastocytosis in a shar-pei. Can Vet J 40 (12), 881-883 PubMed.

Other sources of information

  • Work M & Allerton F (2020) Focus on Shar Pei Fever. BSAVA Companion, Volume 2020, Issue 2, Feb 2020, pp 18-21.
  • Moriello K A (2011) Familial shar-pei fever & hyaluronan. Clin Brief 11, 37.
  • Puppo F, Tintle L, Wong A et al (2005) Recurrent fever in Chinese Shar-Pei dogs is a model of human autoinflammatory diseases: mutational screening in canine MEFV and TNFRSF1A.[Abstract] Fourth International Congress on Systemic Autoinflammatory diseases, November 6-10, Bethesda, MD..

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