Primary cutaneous undifferentiated round cell tumor with concurrent polymyositis in a dog.

A cutaneous poorly differentiated round cell tumor with concurrent, non-suppurative, polymyositis was diagnosed in a hovawart dog. Histochemical staining, immunohistochemistry, and transmission electron microscopy findings suggested that the tumors cells were of myeloid, or possibly natural killer cell origin. The possibility that the concurrent polymyositis may represent a pre-neoplastic or paraneoplastic process is discussed.

Granulomatous interstitial polymyositis and intramuscular neuritis in a dog.

BACKGROUND: Granulomatous myositis is a rare condition in both humans and dogs. In humans it is most frequently related to sarcoidosis, where a concurrent granulomatous neuritis has been reported occasionally. Simultaneous granulomatous myositis and neuritis have been diagnosed previously in dogs (unpublished observations), but have not been studied further. Additional investigations are therefore warranted to characterize this disorder. Here we present a detailed description of concurrent idiopathic granulomatous myositis and granulomatous neuritis in a dog with suspected immune-mediated aetiology. CASE PRESENTATION: The dog presented with dysphonia and paresis in the pelvic limbs and tail. In addition to muscle biopsies being taken for histopathology, magnetic resonance imaging, computed tomography and electrodiagnostics were performed. Muscle biopsies displayed granuloma formation with giant cells and epithelioid macrophages in muscle fibres and nerve branches. Microorganisms were not detected. Long-term treatment with glucocorticoids was clinically successful. Two years after the clinical signs started, the dog presented with signs of sepsis and died. Histopathologically, no granulomatous inflammation could be demonstrated in either muscles or nerves at that time. CONCLUSIONS: This case illustrates a granulomatous interstitial polymyositis and intramuscular neuritis that improved clinically and resolved histologically with glucocorticoid treatment. Idiopathic granulomatous myositis and neuritis should be considered as a differential diagnosis in dogs with clinical signs of neuromuscular disorders.

Acquired myasthenia gravis with concurrent polymyositis and myocarditis secondary to a thymoma in a dog.

Background: Canine thymomas are associated with multiple paraneoplastic syndromes, among which myasthenia gravis (MG) is the most common. Acquired MG is an autoimmune disease characterized by the presence of antibodies against acetylcholine receptors (ACHRs). ACHRs antibodies are the most commonly formed, but the production of antistriational antibodies binding to skeletal and cardiac muscle proteins has also been recorded both in humans and dogs. An association between the occurrence of antistriational antibodies and a severe form of myocarditis, giant cell myocarditis, has been described in humans. Case Description: A 4-year-old mixed-breed dog was referred because of 1 month history of exercise-induced weakness, hypersalivation, and regurgitation. The neurologic examination was indicative of a neuromuscular junction disease, and MG was suspected. A computed tomographic scan examination showed the presence of a megaoesophagus and a thymic mass. Serum antibodies against ACHRs confirmed the diagnosis of MG. Treatment with pyridostigmine was started, and the thymic mass was surgically excised, and a diagnosis of thymoma was confirmed by histology. 24 hours after surgery, the dog developed a third-degree atrioventricular block. Severe arrhythmia and increased troponin serum levels suggested myocarditis which rapidly led to cardiopulmonary arrest. Histopathologic examination of the heart, esophagus and diaphragm revealed a lymphocytic and macrophagic infiltration, consistent with myocarditis and polymyositis. Scattered rare giant multinucleated cells were also detected in the myocardium. Conclusion: To the author's knowledge, this is the first report of thymoma-associated MG with concurrent polymyositis and giant cell-like myocarditis in a dog.

[Trichinella induced polymyositis with unilateral lameness in a dog]. / Polymyositis mit einseitiger Lahmheit im Rahmen einer Trichinellose beim Hund.

A 9-year-old Cairn Terrier was presented for a right thoracic limb lameness of 3-month duration resistant to anti-inflammatory pain treatment. Blood chemistry revealed a highly elevated creatine kinase activity. An orthopedic or vascular etiology of the lameness was excluded by radiographs, computed tomography, and magnetic resonance imaging. Further workup for a neurologic or muscular etiology by electromyography, nerve conduction velocity measurement, and histology of muscle as well as nerve biopsies identified the cause of the lameness. Histology revealed a pyogranulomatous, necrotizing myositis with parasites of the species Trichinella. Furthermore different developmental stages of fungi were detected which were identified as Mucor sp. Treatment with albendazole and itraconazole significantly improved the patient's clinical signs.

Symptomatic tongue atrophy due to atypical polymyositis in a Pembroke Welsh Corgi.

A three-year-old, 7.3-kg, female Pembroke Welsh Corgi exhibited symptomatic tongue atrophy, crinkling of the tip of the tongue, dysphagia and excessive salivation. Neurological examination suggested multiple cranial neuropathy, but polymyositis was diagnosed by magnetic resonance imaging and muscle biopsy. The dog did not respond to prednisolone treatment and died from aspiration pneumonia 22 months after the first presentation. Post-mortem histopathological examination of the tongue revealed marked myofiber loss and fibrosis with multifocal infiltration of mixed mononuclear cells. Similar findings were also observed in the masticatory muscles and quadriceps without abnormality of peripheral nerves or evidence of infection. Symptomatic tongue atrophy occurring in the course of polymyositis has not been reported previously in dogs.

Severe polymyositis and neuritis in a cat.

CASE DESCRIPTION: A 4-year-old domestic shorthair cat was evaluated for a 1-week history of shifting limb lameness that progressed to tetraparesis. CLINICAL FINDINGS: Physical examination revealed generalized muscle atrophy and signs of discomfort when the muscles of the appendicular skeleton were palpated. Neurologic examination revealed diminished myotatic and withdrawal reflexes in all 4 limbs. Results of a CBC indicated mild neutrophilia, and serum biochemical analysis revealed mild hyperalbuminemia and high creatine kinase activity. The cat was anesthetized, and an electromyogram (EMG), CSF sample, and nerve and muscle biopsy specimens were obtained. The EMG revealed positive sharp waves and fibrillation potentials, CSF analysis revealed albuminocytologic dissociation, and histologic examination of muscle and nerve specimens revealed severe myositis and neuritis. Immune-mediated polymyositis and neuritis were suspected. TREATMENT AND OUTCOME: With physical therapy and long-term corticosteroid drug treatment, the cat recovered complete motor nerve function. CLINICAL RELEVANCE: The severity and rapid progression of clinical signs, combined with the EMG abnormalities and histologic findings, could have led to inappropriate euthanasia for this cat. Veterinarians should be aware that immune-mediated polymyositis and neuritis in cats can have an excellent prognosis with appropriate, long-term treatment.

A Mutation in the Mitochondrial Aspartate/Glutamate Carrier Leads to a More Oxidizing Intramitochondrial Environment and an Inflammatory Myopathy in Dutch Shepherd Dogs.

BACKGROUND: Inflammatory myopathies are characterized by infiltration of inflammatory cells into muscle. Typically, immune-mediated disorders such as polymyositis, dermatomyositis and inclusion body myositis are diagnosed. OBJECTIVE: A small family of dogs with early onset muscle weakness and inflammatory muscle biopsies were investigated for an underlying genetic cause. METHODS: Following the histopathological diagnosis of inflammatory myopathy, mutational analysis including whole genome sequencing, functional transport studies of the mutated and wild-type proteins, and metabolomic analysis were performed. RESULTS: Whole genome resequencing identified a pathological variant in the SLC25A12 gene, resulting in a leucine to proline substitution at amino acid 349 in the mitochondrial aspartate-glutamate transporter known as the neuron and muscle specific aspartate glutamate carrier 1 (AGC1). Functionally reconstituting recombinant wild-type and mutant AGC1 into liposomes demonstrated a dramatic decrease in AGC1 transport activity and inability to transfer reducing equivalents from the cytosol into mitochondria. Targeted, broad-spectrum metabolomic analysis from affected and control muscles demonstrated a proinflammatory milieu and strong support for oxidative stress. CONCLUSIONS: This study provides the first description of a metabolic mechanism in which ablated mitochondrial glutamate transport markedly reduced the import of reducing equivalents into mitochondria and produced a highly oxidizing and proinflammatory muscle environment and an inflammatory myopathy.

Dilatation of the right atrium in a dog with polymyositis and myocarditis.

A nine-year-old, female, neutered golden retriever was referred for investigation of weakness. Immune-mediated polymyositis with mixed mononuclear cell inflammation and fibrosis was diagnosed in muscle biopsy specimens from several sites. A soft tissue opacity was noted radiographically cranial to the cardiac silhouette. The dog failed to respond to treatment with prednisolone and was euthanased. At post-mortem examination, the structure observed radiographically was showed to be an enlarged right atrium. Histopathological examination of samples collected at post-mortem confirmed polymyositis. Additionally, mononuclear cell infiltrations and fibrosis were observed in areas of endocardium and/or myocardium in the walls of all four cardiac chambers. Myocarditis has not been reported previously in canine polymyositis but is well recognised in people. Enlargement of the right atrium has also been reported in association with polymyositis and myocarditis in people.

Evaluation of coexisting polymyositis in feline myasthenia gravis: A case series.

Acquired myasthenia gravis (MG) is relatively uncommon in cats. In humans, MG may be associated with other immune-mediated disorders, in particular polymyositis (PM). In this study, we described in-depth electrodiagnostic findings and pathological changes in muscles of cats diagnosed with MG, and assessed the presence of concurrent PM. Six cats with confirmed acetylcholine receptor antibody seropositive MG, and two suspected cases with clinical signs and electrophysiological changes consistent with MG, were reviewed. All animals presented with severe typical signs of generalized weakness and/or fatigability, resembling late-onset MG in humans, in addition to regurgitation. Five cats presented a cranial mediastinal mass, with 3 confirmed as thymoma. Repetitive nerve stimulation revealed a decrement of the compound muscle action potential in all tested cases, starting from low frequencies of stimulation. Serum creatine kinase activity was increased in 6/8 cats. Muscle biopsies performed in 5 cats revealed varying degrees of mixed mononuclear cell infiltrates, positive for the leukocyte markers CD3/CD4/CD8 and CD11b. Further MHC-1/C5b-9 positive sarcolemmal deposits were identified in all tested cases, with or without thymoma. This study documents an association of MG and PM in cats, and provides further support for feline MG as a relevant animal model of human MG.

[The first report of a disseminated idiopathic myofasciitis in a ferret (Mustela putorius furo) from Germany]. / Erstbeschreibung einer disseminierten idiopathischen Myofasciitis bei einem Frettchen (Mustela putorius furo) aus Deutschland.

A 1.5 year old neutered male pet ferret (Mustela putorius furo) was presented with a sudden onset of severe weakness. The ferret was kept with three healthy mates, was vaccinated against distemper regularly and was never ill before presentation. Clinically, the ferret was depressed, had a hyperthermia of 40.3 degrees C, tachypnea and ocular as well as nasal discharge. Blood work revealed a mild neutropenia, blood chemistry a hyperglycemia, hyperbilirubinemia, hypoproteinemia, hypoalbuminemia, hypocalcemia and hyponatremia. Despite intensive therapy including fluid replacement, antibiosis, analgesia and antipyretics, the overall condition of the ferret deteriorated and the animal was euthanized two days later. Necropsy revealed a pyogranulomatous myositis, fasciitis and steatitis of the long hyoid muscles, the esophagus and intestine. Lesions were consistent with the disseminated idiopathic myositis of ferrets. This is the first reported case of this disease in a ferret originated in Germany.

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.

Neospora caninum infection in English Springer Spaniel littermates. Diagnostic evaluation and organism isolation.

Progressive paraparesis developed in four male English Springer Spaniel pups from a litter of five during the first 10 weeks of life. Two of the pups, which had the earliest onset of neurologic signs, were euthanatized without further workup. However, a detailed investigation was completed on the remaining two littermates at 12 weeks of age. Both pups had progressive paraparesis for 3 to 4 weeks before presentation, with one dog developing subsequent asymmetric pelvic limb extensor rigidity. Based on results from neurologic examination, cerebrospinal fluid (CSF) analysis, electrophysiology, and muscle/nerve biopsy, a presumptive diagnosis of protozoal polyradiculitis and polymyositis was made. Necropsy of the most severely affected pup confirmed the clinical diagnosis of inflammatory nerve root and muscle disease but no organisms were found. To increase the potential yield of organisms, the second pup was placed on immunosuppressive doses of corticosteroids and euthanatized 2 weeks later. Numerous organisms were found in lesions in muscle and the central nervous system. Organisms grew in tissue culture and were isolated from the peritoneal fluid of gerbils inoculated with infected tissue. Organisms were not isolated from inoculated mice, guinea pigs, rabbits, and hamsters. No parasites were seen in feces or tissues of three cats fed infected dog tissues. Serologic testing demonstrated a strong positive titer to Neospora caninum in both pups, and electron microscopy showed the characteristic morphology of this parasite.

Multifocal myositis associated with Sarcocystis sp in a horse.

Multifocal myositis was diagnosed in a 7-year-old Quarter Horse gelding on the basis of history and findings on physical examination, serum biochemical analysis, electromyography, and microscopic examination of frozen sections of muscle biopsy specimens. Histologic examination of the muscle specimen revealed multifocal accumulations of histiocytes, lymphocytes, and plasma cells, with attendant myofiber degeneration and necrosis. Parasitic cysts with morphologic characteristics of Sarcocystis sp were found in regions of myocyte degeneration and necrosis, and in regions of normal muscle. Based on a tentative diagnosis of Sarcocystis sp-induced myositis, the horse was treated with trimethoprim/sulfamethoxazole and pyrimethamine for 28 days, phenylbutazone for 5 days, and paddock rest for 30 days. At the end of treatment, the horse had gained 35 kg, its appetite had returned to normal, and muscle mass was returning to normal. Sarcocystis fayeri is the only Sarcocystis sp reported in equine muscle in the United States and is rarely associated with acute myositis or muscle atrophy. The development of clinical signs in this horse could have been the result of an underlying immunosuppression or infection with a particularly pathogenic strain or large infective dose of S fayeri.

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.

Masticatory and skeletal muscle myositis in canine leishmaniasis (Leishmania infantum).

Twenty-four dogs with a parasitologically and serologically established diagnosis of leishmaniasis were studied to investigate the atrophy of the masticatory muscles which commonly occurs in this disease, and to compare the lesions in the masticatory muscles with those in the cranial tibial muscles. The 24 animals were divided into three groups of eight, group A dogs with no muscular atrophy, group B dogs with different degrees of atrophy in the masticatory and skeletal muscles, and group C dogs with similar degrees of atrophy in the masticatory and skeletal muscles. Increased activities of creatine phosphokinase and lactate dehydrogenase were recorded in only some of the dogs in groups B and C, but there were no significant differences between the mean activities in the three groups. Electromyographic changes indicating myopathy and involving both the temporalis and cranial tibial muscles, were observed in two of the dogs in group A, seven of those in group B, and in all the dogs in group C. Muscle histopathology revealed a variable degree of muscle fibre necrosis and atrophy, mononuclear infiltrates and neutrophilic vasculitis in all the dogs except two in group A. Leishmanial amastigotes were found within macrophages and myofibres in 16 of the dogs, some in each group. IgG immune complexes were detected in muscle samples, and circulating antibodies against myofibres were detected in serum samples from all the 24 dogs.

Association of an MHC class II haplotype with increased risk of polymyositis in Hungarian Vizsla dogs.

A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 "graded" controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR = 1.92, p = 0.032). When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR = 4.08, p = 0.00011). Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis.

Polymyositis following Vogt-Koyanagi-Harada-like syndrome in a Jack Russell terrier.

A male Jack Russell terrier developed bilateral uveitis and glaucoma at 1 year of age. Since the ocular disease was painful and unresponsive to treatment, both globes were enucleated. Microscopical evaluation of one enucleated globe revealed panuveitis, with pigment dispersion and phagocytosis consistent with the ocular lesions of canine Vogt-Koyanagi-Harada (VKH)-like syndrome. Three years later the dog was represented with severe muscle disease and skin lesions. Due to rapid clinical deterioration the dog was humanely destroyed. Necropsy examination revealed lichenoid interface inflammation in the skin and mucous membranes, with pigmentary incontinence consistent with VKH-like syndrome and lymphocytic and histiocytic polymyositis with marked muscle atrophy. Canine VKH-like syndrome is an autoimmune disease that targets melanocyte antigens. Some human patients with VKH disease develop additional autoimmune diseases. To our knowledge this is the first reported case of polymyositis subsequent to VKH-like disease in a dog. In addition, VKH-like disease has not been previously reported in a Jack Russell terrier.