Familial cutaneous vasculopathy of German shepherds: clinical, genetic and preliminary pathological and immunological studies.

A genodermatosis affecting the German shepherd breed has been recognized in 26 dogs in Ontario since 1991. Clinical signs, first noted in young puppies,are manifested as pyrexia and lethargy. The main cutaneous lesions are footpad swelling and depigmentation,but there is also crusting and ulceration of ear tips and tail tips, and focal depigmentation of the nasal planum. Affected puppies show no consistent abnormalities in hematological or biochemical parameters, and immunological tests (antinuclear antibody and rheumatoid factor titer,immunoglobulin levels, and CD4+ and CD8+T-lymphocyte percentages) are normal. Bone marrow analysis has shown myeloid hyperplasia in 5 of 7 cases and myelofibrosis has been detected in 1 case. All but 3 of the 19 clinical cases have been strongly positive for platelet factor-3; however, normal puppies routinely develop positive platelet factor-3 tests. Furthermore, affected pups all had normal numbers of platelets on repeat complete blood counts.Light microscopic examination of footpad biopsies reveals a multifocal nodular dermatitis in which neutrophils and mononuclear inflammatory cells surround foci of dermal collagenolysis, and degenerative and inflammatory vessel lesions. Depigmented lesions have a mild, cell-poor, interface dermatitis,characterized by single cell necrosis of the basal cells, in addition to the nodular dermatitis. Similarities and differences between this disease,a condition known as collagen disorder of the footpads of German shepherds and other forms of cutaneous vasculitis in the dog are discussed. The cause and the pathogenesis of the disease are yet to be elucidated;however, pedigree analysis indicates an autosomal recessive inheritance pattern. Hypersensitivity reactions, directed against normal or damaged self-collagen, may be involved. The role of cell-mediated immunity against native or altered collagen is an area worthy of further investigation.