Ulcerative dermatosis of the Shetland sheepdog and rough collie dog may represent a novel vesicular variant of cutaneous lupus erythematosus

A syndrome of ulcerative dermatitis (UDSSC) previously has been described as unique to the Shetland sheepdog and rough collie dog. The pathogenesis of this disease is poorly understood and it has been suggested that it may be a variant of canine dermatomyositis (DM) which is also seen in these breeds. Information on the clinical presentation and previous medical history was collected from five Shetland sheepdogs and three rough collie dogs previously diagnosed with UDSSC. Characteristic features of the disease were adult onset in the summer months with annular, polycyclic and serpiginous ulcerations distributed over sparsely haired areas of the body. Skin biopsies taken from active lesions were compared in a blinded fashion with histological sections from seven Shetland sheepdogs and one rough collie with DM. Dermatomyositis was characterized histologically as a cell poor interface dermatitis associated with follicular atrophy. In contrast, the lesional pattern of UDSSC is that of a lymphocyte-rich interface dermatitis and folliculitis with vesiculation at the dermal–epidermal junction. The authors conclude that these represent two distinct diseases and that UDSSC may be a vesicular form of cutaneous lupus erythematosus seen in the adult rough collie dog and Shetland sheepdog.     

Eleven cases of vesicular cutaneous lupus erythematosus in Shetland sheepdogs and rough collies: clinical management and prognosis

Abstract   A cutaneous ulcerative disease is recognized to affect the adult Shetland sheepdog and rough collie. This has a distinct clinical and histological appearance consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). Retrospective information on the clinical outcome and response to therapy was collected from 11 cases of histologically confirmed VCLE. In 8/11 dogs the onset of disease was in the summer; in three dogs recrudescence occurred in subsequent summers. In eight dogs the skin disease was judged to be 75–100% controlled with therapy after a minimum follow-up of 9 months. Successful treatment in seven of these cases comprised immunosuppressive doses of oral glucocorticoids, alone (one dog), in combination with azathioprine (five dogs) and doxycycline (one dog). One case responded to topical fluocinolone. Three dogs were euthanased for reasons directly related to the disease, one prior to initiating any therapy. Vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog can be a debilitating skin disease which is best managed with aggressive immunosuppressive therapy. Sun avoidance or the use of sunscreens is an important additional management recommendation.     

Linkage of dermatomyositis in the Shetland Sheepdog to chromosome 35

Dermatomyositis is an inflammatory disease of the skin and muscle and is most commonly found in the Shetland sheepdog. Both the clinical presentation and the age of onset of dermatomyositis vary widely, and the inability to diagnose dermatomyositis before clinical symptoms ensue has made control of the disease difficult. Identification of a genetic marker that cosegregates with dermatomyositis would facilitate the development of a DNA-based test for the early detection of affected dogs. We report the use of linkage disequilibrium (LD) mapping to identify linkage to phenotypic dermatomyositis in the Shetland sheepdog. One marker, microsatellite marker FH3570 on canine chromosome 35, had evidence of LD (P=0.00002). Further studies are necessary to narrow the region harbouring the dermatomyositis locus, identify candidate genes and determine mode of inheritance.     

Dermatomyositis in five Shetland sheepdogs in the United Kingdom

Five cases of dermatomyositis in four Shetland sheepdog puppies and one adult bitch are described. The dogs all had well-defined patches of scaling, crusting and alopecia over the muzzle, periorbital skin and distal limbs, and the tail, perineum and pinnae were affected in some of them. The affected puppies were all sired by the same stud dog. The affected adult bitch was unrelated to the puppies. Three of the four dogs tested had high serum creatine kinase concentrations and electromyographic abnormalities were detected in three of the four dogs tested. The histological changes observed in the skin of four of the dogs strongly supported the diagnosis of dermatomyositis, and in the fifth dog they were compatible with this diagnosis. Two of the puppies were euthanised shortly after being diagnosed. In the other two puppies and the adult the disease remains stable and non-progressive 15 to 18 months after diagnosis. The sire of the four affected puppies has been used extensively because it was considered to be genetically clear of collie eye anomaly.     

Immunopathology of vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog: a canine homologue of subacute cutaneous lupus erythematosus in humans

Clinical and histological features of an erosive disease in the rough collie and Shetland sheepdog are most consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). This paper reports the immunopathological findings of canine VCLE using samples from 17 affected dogs. Lesional skin sections were stained with monoclonal antibodies specific for CD3 (11 dogs) or a panel of monoclonal antibodies specific for leukocyte antigens (two dogs). Apoptotic cells were detected using the TUNEL method in 12 cases. Direct (14 dogs) and indirect immunofluorescence tests (five dogs) were also performed. Circulating antibodies to extractable nuclear antigens (ENA) were surveyed in 11 dogs by immunoblotting and ELISA. The predominant cells at the dermal-epidermal interface were identified as CD3(+) T lymphocytes expressing CD4 or CD8 and CD1(+) dendritic antigen presenting cells. In 7/12 dogs (58%), apoptosis of basal keratinocyte nuclei was present. Up-regulation of MHCII and ICAM-1 was observed on basal keratinocytes from the two dogs examined. Direct immunofluorescence revealed deposition of immunoglobulins bound to the cytoplasm of keratinocytes (6/14 dogs; 43%), to the dermal-epidermal junction (7/14 dogs; 50%), or to superficial dermal venules (13/14 dogs; 93%). Circulating IgG auto-antibodies targeting one or more ENA were detected in nine (82%) and eight (73%) of 11 dogs by immunoblotting and ELISA, respectively. These auto-antibodies recognized Ro/SSA and/or La/SSB in four (36%) and six (55%) of 11 dogs respectively by these two methods. Altogether, results of these studies provide evidence supporting the hypothesis that canine VCLE is an immunological homologue of subacute cutaneous lupus erythematosus in humans.     

Analysis of uroliths from cats and dogs in New Zealand, 1993-96

AIMS: Canine and feline uroliths were analysed to determine the prevalence of particular types of urolith and the dog breeds at risk. METHODS: Three hundred and sixty-nine uroliths recovered from 316 dogs and 53 cats between November 1993 and December 1996 were analysed by X-ray diffraction, and by infrared spectrometry where X-ray diffraction alone was non-diagnostic. RESULTS: Bitches of small breeds especially Welsh corgi and Bichon frise, were most frequently affected. Struvite was the most common urolith (204 dogs). Oxalate (60 dogs) was the second most prevalent urolith identified, followed by cystine (24 dogs). The breeds producing cystine calculi were: Dalmatian, Bassett hound, Borzoi, Newfoundland, Shetland sheepdog, Labrador, Chihuahua, Fox terrier, English bulldog, Bichon frise, Doberman pinscher, Border collie. Silica uroliths were identified for the first time in New Zealand. All feline uroliths were struvite. CONCLUSION: The results are useful in determining the prevalence of specific types of urolith in New Zealand and the breeds at risk of forming them.     

Survey with follow-up of 67 dogs with testicular sertoli cell tumours

Sixty-seven cases of canine sertoli cell tumour are reviewed. The mean age at diagnosis was 9.5 years (sd +/- 2.1, range 3 to 17). The most commonly affected breeds were boxer, cairn terrier, labrador retriever, border collie, German shepherd and rough collie. The left side was affected in 28 dogs (42 per cent), the right in 35 (52.5 per cent) and both sides in four (6 per cent). Twenty testicles were abdominal (left, seven; right, 13), seven were inguinal (left, four; right, three) and 44 were scrotal (left, 21; right, 23). Hormonal signs were evident in 38 (57 per cent) animals (feminisation with alopecia in 21, symmetrical alopecia alone in 17). Other types of testicular tumours were found in 12 dogs (18 per cent) of this series. Of 42 dogs which were castrated and discharged, 38 were available for follow-up study and survived for between one week and five years. Two of the 15 dogs which were subject to post mortem examination had metastases. Two others which died after failure of remission, or a recurrence of the hormonal changes probably also had metastases. Two of the 25 dogs which were presented initially for other reasons, but had sertoli cell tumours, were found to have metastases post mortem. The boxer, cairn terrier, border collie, Shetland collie and pekingese had a higher risk of sertoli cell tumour than other breeds.     

Extradural spinal,bone marrow,and renal nephroblastoma

A 1-year-old, female intact Shetland sheepdog presented with acute onset of neurological signs. Physical examination revealed a large abdominal mass. Neurological examination revealed multifocal disease with neck pain, short-strided forelimbs, and hind-limb paresis with loss of tail and anal tone. Blood work, imaging techniques, cytopathology, and histopathology led to a diagnosis of renal, bone-marrow, and extradural spinal nephroblastoma. This report documents potential clinical and pathological manifestations of canine nephroblastoma that have not been previously reported.     

Molecular genetic and expression analysis of alpha-tocopherol transfer protein mRNA in German shepherd dogs with degenerative myelopathy

Degenerative Myelopathy (DM) is a progressive neurological disorder of the spinal cord preferentially occurring in German shepherd dogs. The pathogenesis of the disease is unknown. However, there are indications that vitamin E deficiency may be involved in the pathogenesis of DM. Therefore, we analyzed the expression and the nucleotide sequence of the canine alpha-tocopherol transfer protein (alpha Ttp) of German shepherd dogs with DM in order to determine whether a deficiency or a defect of the alpha Ttp could be a primary factor in the pathogenesis of DM, as found in human patients with Ataxia with vitamin E deficiency (AVED). The cDNA of the coding region of the canine alpha Ttp-mRNA was generated from total liver RNA using RT-PCR and 5' RACE technique. We determined the sequence of 707 out of 834 base pairs or 84.8% of the canine alpha Ttp coding region. Sequence comparison of canine alpha Ttp between affected and control dogs revealed no differences in either nucleotide or predicted amino acid sequence. Using Northern blot analysis alpha Ttp-mRNA expression was solely found in the liver of the dogs, rats and humans, while various other organs showed no alpha Ttp-mRNA expression. No significant differences in expression levels of canine alpha Ttp mRNA were found between DM and control dogs. Our data suggest that the canine alpha Ttp gene is unlikely to be involved in the pathogenesis of DM in German shepherd dogs.     

Clinical and laboratory features of a severe form of von Willebrand disease in Shetland sheepdogs

Ten clinically affected Shetland Sheepdogs were evaluated to define their severe bleeding diathesis and were determined to have von Willebrand factor antigen (vWF:Ag) values less than 0.1% by ELISA assay. The virtual absence of vWF protein by ELISA assay and on multimeric analysis was diagnostic of either homozygosity or probable double heterozygosity for the canine von Willebrand disease (vWD) gene. Clinically affected dogs have type-III vWD and are the offspring of 2 heterozygous parents carrying type-I vWD. Twenty-three percent (1,428 dogs) of the more than 6,000 Shetland Sheepdogs screened for vWD at our facility since 1982 tested within the heterozygous carrier range for the common type-I form of this inherited disorder. Veterinarians and breeders should be aware of the potential for bleeding associated with elective and medical procedures in Shetland Sheepdogs and should use caution when breeding carriers of vWD because of the risk of producing clinically affected offspring with severe type-III vWD.     

Pathological features of arrhythmogenic right ventricular cardiomyopathy in middle-aged dogs

The hearts of four dogs (a 4-year-old Shetland sheepdog, a 4-year-old Labrador retriever, a 5-year-old English Bulldog, and a 6-year-old Dalmatian; three males and one female), that had died suddenly and had been clinically diagnosed as having arrhythmogenic right ventricular cardiomyopathy (ARVC), were studied post mortem. At the cut surface, all four hearts showed mild to moderate hypertrophy of the left and right ventricular free walls and ventricular septum, with grayish-white tissue replacement of the myocardium to various degrees. Histologically, all had typical right ventricular features of ARVC and morphological evidence of left ventricular and ventricular septal involvement. Two main histological patterns were identified: a fatty type (two cases) and a fibrofatty type (two cases). With either type, myocardial replacement by fatty or fibrofatty tissue were detected in both ventricles, but were more severe in the right ventricle, where they usually became transmural. Furthermore, this myocardial replacement was more severely seen in the epimyocardium and midmyocardium; the endomyocardium was less severely affected. On the basis of the present observation, it is evident that, in dogs, the disease process of ARVC affects both the right and left ventricles, although the striking pathological feature is right ventricular involvement. The pathological evidence of biventricular involvement in these canine cases of ARVC may represent a wider spectrum of the disease than has previously been recognized, suggesting that, in dogs, this disease should no longer be considered as limited to the right ventricle.     

The effects of skin disease on the penetration kinetics of hydrocortisone through canine skin in vitro

This study investigated the effects of allergic skin disease on the penetration kinetics of hydrocortisone through canine skin in vitro. Full-thickness lesional and nonlesional (normal) skin was removed from the dorsal lumbosacral and dorsocaudal thoracic regions, respectively, of five canine cadavers. The dogs were suspected of having flea allergy dermatitis based on their distribution and types of skin lesions. Nonlesional skin was confirmed to be histologically normal, and the histopathology of the lesional skin was consistent with allergic dermatitis. Excised skin was clipped, mounted in Franz-type diffusion cells, and the transdermal penetration of a saturated, radiolabelled hydrocortisone solution was measured over 30 h. When the penetration data for all five dogs were pooled, a restricted (or residual) maximal likelihood mixed model predicted that the permeability coefficient and pseudosteady-state flux of hydrocortisone was more than twice as great (95% confidence interval 1.55-2.71 times as great; P < 0.0001) through lesional compared with nonlesional skin. There was no significant difference in the lag time for hydrocortisone penetration through lesional compared with nonlesional skin of the dogs. This study has confirmed that the transdermal penetration of hydrocortisone may be altered, typically increased twofold, but could be as high as 10-fold, through lesional compared with nonlesional skin of dogs with suspected flea allergy dermatitis. This is likely to be affected by variables such as disease severity, concurrent infections and interindividual differences in skin characteristics.     

Resolution of skin lesions and long-term survival in a dog with superficial necrolytic dermatitis and liver cirrhosis

A nine-year-old, neutered female Shetland sheepdog was presented with crusted, ulcerative skin lesions affecting the footpads, commissures of the lips and the lateral canthi of the eyes. Histopathological examination of skin biopsies revealed changes consistent with superficial necrolytic dermatitis and biochemical analysis demonstrated elevated liver enzymes. Abdominal radiography revealed a small liver which, on ultrasonography, appeared diffusely mottled and showed changes suggestive of periportal fibrosis. On exploratory laparotomy, the pancreas appeared normal, but the liver was small and had multiple nodules throughout the parenchyma. This appearance was confirmed as cirrhosis on histopathological examination. The dog was placed on a hepatic support diet and treated with colchicine, essential fatty acid supplementation and raw egg yolks. After four weeks, the skin lesions had resolved and the dog remained free of clinical signs over a 22-month follow-up period.     

Gene therapy using non-viral peptide vector in a canine systemic lupus erythematosus model

Although viral vectors are commonly used for therapeutic gene delivery, their applications are limited due to their specific cell membrane receptor-mediated infection and host immune response. In the present study, we constructed a non-viral peptide vector and applied it in the treatment of experimentally induced systemic lupus erythematosus-like disease in dogs. For therapeutic gene construction, the extracellular domain of canine CTLA-4, and the CH2-CH3 domains of canine immunoglobulin alpha constant region were inserted between the cytomegalovirus promoter and poly-adenylation sequence of bovine growth hormone. The constructed therapeutic gene was ligated to the non-viral synthetic peptide vector and was applied to systemic lupus erythematosus-like disease induced dogs. After gene therapy, clinical signs of systemic lupus erythematosus were reduced dramatically: the anti-nuclear antibody titers and urine protein/creatinine ratios were recovered to normal values, and the skin regained its normal histological features. The peptide vector did not show either tissue specific tropism or host induced immune response.     

A comparison of adherence by four strains of Staphylococcus intermedius and Staphylococcus hominis to canine corneocytes collected from normal dogs and dogs suffering from atopic dermatitis

The aim of this study was to compare the adherence of four strains of Staphylococcus intermedius and a single strain of Staphylococcus hominis to corneocytes from both normal dogs and dogs suffering from atopic dermatitis. Cells from the skin surface, corneocytes, were collected from 10 normal dogs and 10 dogs suffering from atopic dermatitis. Four strains of S. intermedius, three isolated from canine pyoderma skin lesions (strains A, B and C), and one isolated form from canine synovial membrane sample from a case of septic arthritis (strain D) were compared. S. hominis, which is not normally associated with canine disease, was also evaluated for its ability to adhere to canine corneocytes. S. hominis did not adhere to canine corneocytes. All four strains of S. intermedius adhered well to canine corneocytes collected from both normal and atopic dogs. All strains of S. intermedius showed statistically greater adherence to corneocytes collected from atopic dogs compared with those collected from normal dogs. It was concluded that the adherence assay employed here showed that S. hominis does not adhere to canine corneocytes, S. intermedius adheres preferentially to atopic corneocytes.     

Pilot investigation of a model for canine atopic dermatitis: environmental house dust mite challenge of high-IgE-producing beagles, mite hypersensitive dogs with atopic dermatitis and normal dogs

Although canine atopic dermatitis (cAD) is common, few models are available. The aim of this study was to evaluate high-IgE beagles epicutaneously sensitized to house dust mite (HDM) as a possible model for cAD. Six high-IgE beagles were environmentally challenged with HDM using various doses and protocols. Similar challenge protocols were used in positive and negative control dogs: three dogs with naturally occurring cAD and positive intradermal skin test (IDT) to HDM and three normal dogs without history of skin disease and negative IDT to HDM. All high-IgE beagles and all atopic dogs developed severe cutaneous lesions and pruritus after challenge. Lesions were erythematous papules and macules in contact areas such as face, ears, ventral abdomen, groin, axillae and feet. They were first visible after 6 h and increased in severity over time. No normal dog developed pruritus or lesions. Biopsies of representative lesions in the high-IgE beagles were taken for histopathology and immunohistochemistry. There was superficial perivascular dermatitis with mononuclear infiltrates and spongiosis. Lymphocytes and eosinophils accumulated in small epidermal micro-abscesses with hyperplasia of epidermal IgE-bearing dendritic cells. These findings suggest that this colony of high-IgE beagles develops a dermatitis that clinically, histopathologically and immunologically resembles the naturally occurring canine disease. It is also concluded that this modality of challenge is not irritating to normal dogs but induces flare-ups in hypersensitive atopic dogs.     

The role of allergy in the development of canine pyoderma

Pyoderma is commonly seen in canine veterinary practice and usually occurs as a complicating factor in other primary conditions. Allergic skin disease is often the underlying cause but the precise relationship between allergy and infection is unknown. Our studies have investigated the relationship between bacterial proliferation at the skin surface and hypersensitivity reactions with the skin. Hypersensitive dogs were shown to have significantly higher surface counts of staphylococci than normal controls and these bacteria were concentrated in the more superficial layers of the stratum corneum. Intradermal injection of staphlococcal antigens in normal dogs elicited epidermal damage similar to that seen in clinical disease. Preliminary autoradiographic studies using a model of canine skin hypersensitivity reactions showed that percutaneous absorption of radiolabelled staphylococcal antigens was increased by mast cell degranulation. These findings suggest that a major role of hypersensitivity reactions in the pathogenesis of pyoderma may be via an effect on epidermal permeability, promoting penetration of staphylococcal antigens from the stratum corneum which then cause the lesions of pyoderma. Hypersensitivity reactions may also lead to changes in the skin surface microclimate leading to increased bacterial counts on the skin surface, so exacerbating the condition.     

Skin lesions in canine leishmaniasis

Forty-three dogs affected by canine leishmaniasis (CL) with skin lesions have been studied clinically and histopathologically. Identification of leishmaniads in tissues was achieved using indirect immunoperoxidase staining. According to both macroscopic and microscopic lesions, four different dermatological patterns have been observed. Twenty-six dogs showed alopecia and desquamation as the main skin lesions. Histologically a diffuse non-suppurative dermatitis, with numerous leishmaniads inside macrophages was present. Ten animals showed skin ulcerations on limbs, especially over articulations. Histologically, the number of leishmaniads was very reduced. Five animals presented a generalised nodular disease. Each nodule corresponded with a focal accumulation of macrophages, multinucleated giant cells and lymphocytes, with a high number of parasites. Finally, two dogs presented generalised skin pustules. The possible pathogenesis and the differential diagnosis of each form is discussed.