DERMATITIS AND RHINOSINUITIS CAUSED BY CURVULARIA SPECIES IN A CHINESE GORAL (NAEMORHEDUS GRISEUS).

Curvularia spp. are globally distributed saprophytic fungi, classified in the literature as dematiaceous, or darkly pigmented fungi. These fungi have been increasingly recognized as causing cutaneous, ocular, respiratory, and central nervous system infections in humans, but have been infrequently documented as pathogens in the veterinary literature. A 5-yr-old male Chinese goral (Naemorhedus griseus) presented with bilateral fungal dermatitis of the pinnae, and subsequent pyogranulomatous rhinosinusitis. Clinical signs included epistaxis, mucosanguineous nasal discharge, and dyspnea. Sequential histologic examinations of cutaneous and nasal lesions revealed pyogranulomatous inflammation with extracellular and phagocytized nonpigmented yeasts. Fungal culture and polymerase chain reaction identified Curvularia sp. The absence of pigmentation in tissue in this case suggests that pigmentation may not be a consistent histologic finding for this fungus, emphasizing the importance of molecular identification to prevent misidentification. Despite intensive interventions in this goral, the disease progressed, and was ultimately fatal.

Beyond the MHC: A canine model of dermatomyositis shows a complex pattern of genetic risk involving novel loci.

Juvenile dermatomyositis (JDM) is a chronic inflammatory myopathy and vasculopathy driven by genetic and environmental influences. Here, we investigated the genetic underpinnings of an analogous, spontaneous disease of dogs also termed dermatomyositis (DMS). As in JDM, we observed a significant association with a haplotype of the major histocompatibility complex (MHC) (DLA-DRB1*002:01/-DQA1*009:01/-DQB1*001:01), particularly in homozygosity (P-val = 0.0001). However, the high incidence of the haplotype among healthy dogs indicated that additional genetic risk factors are likely involved in disease progression. We conducted genome-wide association studies in two modern breeds having common ancestry and detected strong associations with novel loci on canine chromosomes 10 (P-val = 2.3X10-12) and 31 (P-val = 3.95X10-8). Through whole genome resequencing, we identified primary candidate polymorphisms in conserved regions of PAN2 (encoding p.Arg492Cys) and MAP3K7CL (c.383_392ACTCCACAAA>GACT) on chromosomes 10 and 31, respectively. Analyses of these polymorphisms and the MHC haplotypes revealed that nine of 27 genotypic combinations confer high or moderate probability of disease and explain 93% of cases studied. The pattern of disease risk across PAN2 and MAP3K7CL genotypes provided clear evidence for a significant epistatic foundation for this disease, a risk further impacted by MHC haplotypes. We also observed a genotype-phenotype correlation wherein an earlier age of onset is correlated with an increased number of risk alleles at PAN2 and MAP3K7CL. High frequencies of multiple genetic risk factors are unique to affected breeds and likely arose coincident with artificial selection for desirable phenotypes. Described herein is the first three-locus association with a complex canine disease and two novel loci that provide targets for exploration in JDM and related immunological dysfunction.

[Dermatomyositis in a family of Working Kelpies].

Eight members of a family of Working Kelpies were presented with signs compatible with dermatomyositis. Alopecia, crusts, ulcerations of the skin, depigmentation of nasal planum and lips, onychodystrophy and atrophy of the masticatory muscles were present with varying degree. Histopathology of the skin, but not from muscles was performed in three dogs and confirmed the clinical diagnosis. Different immunomodulating drugs (steroids, cyclosporine, mycophenolate mofetil, pentoxifylline, doxycyline/niacinamid, omega-3 fatty acids and vitamin E) were used with variable success. Dermatomyositis is an immune-mediated disease and a genetic predisposition is known in humans and certain canine breeds, mainly Shetland Sheepdogs and Collies, but also for the Beauceron. The responsible genes have not been identified so far. It is assumed that the Working Kelpie derives from the Collie which could explain a hereditary predisposition in the Kelpie.

Dermatomyositis-like disease in a Rottweiler.

BACKGROUND: Canine dermatomyositis is a hereditary disease described in collies and Shetland sheep dogs and their cross-breeds. A similar disease, called dermatomyositis-like disease, has been described occasionally in other breeds but never in the Rottweiler. HYPOTHESIS/OBJECTIVES: We report on the clinicopathological findings associated with dermatomyositis-like disease in a Rottweiler. ANIMAL: A 7-month-old female Rottweiler was referred for dermatological abnormalities, regurgitation and weakness. Cutaneous abnormalities included alopecia, crusting and scaling on the inner surface of the pinnae, the tip of the tail, periorbital and perilabial skin. The dog also presented onychogryphosis and onychalgia. METHODS: Complete blood count, serum biochemistry panel, thoracic radiographs, electromyography, nerve-conduction studies and skin and muscle biopsies were performed. RESULTS: Megaoesophagus, pneumonia, ischaemic dermatopathy and generalized myositis were documented. The final diagnosis was dermatomyositis-like disease. CONCLUSIONS AND CLINICAL IMPORTANCE: This is the first report of dermatomyositis-like disease in a Rottweiler.

Ischemic dermatopathies.

The ischemic dermatopathies are a group of vasculopathic diseases that share clinical and histologic features but result from variable causes. Generalized ischemic dermatopathies are typically characterized by atrophic lesions with erythema, scale/crust, erosions/ulcerations, and pigmentary changes. Lesions may affect the toes, tail tip, pinnal margins, bony prominences, or any combination of these areas. Familial dermatomyositis (FDM) most commonly occurs in juvenile collies and Shetland sheepdogs. Ischemic reactions to rabies vaccines may mimic FDM and can occur in any breed. The most reliable symptomatic therapy for any form of ischemic dermatopathy is the combination of pentoxifylline and vitamin E.

Analysis of gene transcript profiling and immunobiology in Shetland sheepdogs with dermatomyositis.

Dermatomyositis (DM) is a canine and human inflammatory disease of the skin and muscle that is thought to be autoimmune in nature. In dogs, DM occurs most often in the rough collie and Shetland sheepdog. Characteristic skin lesions typically develop on the face, ears, tail, and distal extremities. The severity of lesions varies and is thought to increase with stressful stimuli. Previous studies in the collie suggest that DM is inherited in an autosomal dominant fashion with incomplete penetrance. The work presented here concerns gene transcripts profiling and immunobiology of DM in the Shetland sheepdog. Gene transcript profiles were generated for affected and normal skin using a canine-specific oligonucleotide array having 49,929 probe sets. Two-hundred and eight-five gene transcripts, many of which are involved in immune function, were found to be differentially regulated in these tissues. Also reported are Western blot, immunohistochemistry, and immunofluorescence analyses which showed that staining patterns with sera from normal and affected dogs are quite similar. While our work suggests that canine DM is a disease that may be immune mediated, it did not detect the production of specific disease-associated autoantibodies.

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.

Canine inflammatory myopathies: a clinicopathologic review of 200 cases.

A retrospective study was performed on 200 randomly selected cases of inflammatory myopathy in dogs from diagnostic muscle biopsies received at the Comparative Neuromuscular Laboratory, University of California, San Diego. The most common clinical signs in dogs diagnosed with an inflammatory myopathy were generalized weakness, stilted gait, dysphagia, masticatory or generalized muscle atrophy, inability to open the jaw, megaesophagus, and dysphonia. Myalgia was rarely described. Age of onset ranged from 0.25 to 14 years. Genders were equally represented. Breed distribution approximated the 2002 American Kennel Club registration statistics (r = .85) with the notable exception of Boxers and Newfoundlands. From the results of muscle biopsies, clinical signs, and presence or absence of antibodies against type 2M fibers, dogs were classified as a generalized inflammatory myopathy (gIM)--including immune-mediated polymyositis; infectious and preneoplastic myositis; and, rarely, dermatomyositislike or overlap syndromes or unclassified myositis-or a focal inflammatory myopathy (flM)--including masticatory muscle and extraocular myositis. Average creatine kinase (CK) and aspartate aminotransferase (AST) concentrations in gIMs were significantly higher than those with fIMs (P < .05). Neoplasia developed in 12 of 200 dogs within 12 months of diagnosis of polymyositis, with lymphoma diagnosed in 6 of 32 Boxers. Inflammatory myopathy was associated with antibody titers against infectious diseases in 38 dogs. Neospora caninum and Hepatozoon americanum cysts were found in tissues of 2 dogs not serologically tested. Antibodies against an unidentified sarcolemmal antigen were found in 9 of 19 Newfoundlands with polymyositis. The spectrum of canine inflammatory myopathies can be broad, with infectious etiologies relatively common, and can include preneoplastic and uncharacterized syndromes.

Therapeutic response to pentoxifylline and its active metabolites in dogs with familial canine dermatomyositis.

Ten dogs diagnosed with familial canine dermatomyositis based on clinical findings and skin biopsy results were treated PO with pentoxifylline (25 mg/kg twice daily) for 3 months. Blood and urine samples were collected biweekly for complete blood counts, serum chemistries, and urinalysis. Additionally, serum was analyzed for pentoxifylline and its two primary metabolites (metabolites 1 [M1] and 5 [M5]); physical examinations were performed; and skin lesions were photographed and subjectively scored biweekly. The median time to response (regrowth of hair) was 6 weeks (range = 4 to 10 weeks). Clinical chemistries, hematology, and urinalysis variables did not differ between the first sampling time and the final evaluation (Week 12). In general, pentoxifylline and its two metabolites were detectable only at the peak (3-hour) sampling time. M5 concentrations were the highest of the three compounds at each sampling time and were characterized by the least variability. Statistical differences in concentrations between Week 2 and Week 12 did not exist. Four of the 10 dogs were characterized as having a complete clinical response to treatment, and six dogs had a partial response. Based on these responses, 25 mg/kg every 12 hours appeared to be an effective beginning dosage of pentoxifylline for dogs with familial canine dermatomyositis. Because of the variability in disposition, including metabolite formation, monitoring of pentoxifylline concentrations may not offer a therapeutic advantage.

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.

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.

Immune-mediated muscle disease.

The immunopathogenic mechanisms responsible for myasthenia gravis, polymyositis, masticatory myopathy, and dermatomyositis are discussed in light of their relevance to the clinical disease. Current thinking concerning these disorders is presented as a prelude to further research and greater understanding.

Severe secondary amyloidosis in a dog with dermatomyositis.

A male collie aged 5 years 10 months, which developed dermatomyositis at 2 months of age, died from severe secondary amyloidosis. Amyloid deposition was most severe in renal glomeruli and produced renal failure. Amyloidosis has been reported in man with immune-mediated disorders including rheumatoid arthritis, systemic lupus erythematosus and dermatomyositis. It is possible that the inflammation in this case of familial canine dermatomyositis may have predisposed to the development of amyloidosis.

Complement levels in dogs with familial canine dermatomyositis.

CH50, C4, C2, and C3 levels were evaluated in 7 dogs affected with dermatomyositis and in 22 control dogs. Dogs with dermatomyositis did not have clinical evidence of active disease at the time of serum collection for complement assays. No absolute complement component deficiency was identified in dermatomyositis-affected dogs in this study; however, a statistical difference in C2 was identified between control dogs of non-collie breeds and control collies, suggesting there may be a breed difference in complement levels.

The cutaneous histology of dermatomyositis in collie dogs.

Cutaneous lesions of 36 collie dogs affected with dermatomyositis were reviewed. The most common histologic features were follicular atrophy and perifollicular inflammation in 30 dogs, which correlated with alopecia clinically. Other less common findings included formation of colloid bodies, basal cell vacuolation, and subepidermal vesiculation. Results indicated that the most diagnostic cutaneous histologic features of dermatomyositis may be follicular atrophy and inflammation.