RESULTADOS Y DISCUSIÓN

In inflammatory myopathies, also referred to as myositis, myofibre injury is directly caused by the actions of inflammatory cells. Inflammatory myopathies can occur with bacterial, parasitic, fungal and viral infections, or be immune-mediated.120_.

1.4.3.1 Bacterial myositis

Bacteria can be introduced into muscle by direct penetration (wounds and surgery), haematogenous spread, or extension from a local infection such as arthritis. Pyogenic bacteria such as streptococci and staphylococci are frequently involved,141 _{and cause a}

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muscle shows necrosis of myofibres with infiltrates of inflammatory cells and the presence of bacteria, but serum CK and AST activities often remain normal.141 _In

livestock, particularly cattle, sheep and horses, various clostridial species (including

Clostridium perfringens, C. septicum, C. novyi and C. chauvoei)142 _{can cause fatal}

haemorrhagic myonecrosis through the production of toxins under anaerobic

conditions. Clostridial myositis is rare in dogs but has been reported, and in one case was attributed to the use of a contaminated needle for intramuscular injection.143, 144

Myositis in dogs has also been reported in cases of leptospirosis,145, 146 _{but the disease}

typically presents with more severe systemic signs attributable to renal and liver injury.146 _{Cases of leptospirosis in dogs in New Zealand are most commonly associated}

with Leptospira interrogans serovars copenhageni and pomona, and in the past, most clinical cases were reported in the Auckland and Waikato regions.147 _{More recently}

however, antibodies to these serovars, as well as L. borgpetersenii serovars hardjo and

ballum, have been detected in dogs throughout New Zealand, with breeds of working

farm dogs shown to be at greater risk of exposure to L. borgpetersenii serovar hardjo.

1.4.3.2 Parasitic myositis

Protozoal organisms and nematodes may be found incidentally within muscle, or may cause significant clinical disease. In herbivores, rodents, pigs, birds and reptiles, protozoal cysts of Sarcocystis spp. are a common incidental finding120 _{and do not}

typically incite an inflammatory response unless they rupture. In dogs, Neospora

caninum or Toxoplasma gondii protozoal organisms are able to infect skeletal and

cardiac myocytes and cause an inflammatory myopathy, although neurological signs often predominate.118, 148 _{Dogs are intermediate hosts for T. gondii and definitive hosts}

for N. caninum, and can be infected by these protozoal organisms through the ingestion of bradyzoites in tissue cysts of intermediate hosts, or ingestion of

sporulated oocysts in cat faeces (Toxoplasma).149 _{Bradyzoites develop into tachyzoites}

in the gastrointestinal tract, and tachyzoites then spread throughout the body in the lymphatic and vascular systems before forming tissue cysts is tissues such as skeletal and cardiac muscle.150 _{Histologically, polymyositis caused by Neospora in dogs is}

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characterised by multifocal infiltrates of lymphocytes, plasma cells and

macrophages,151 _{and in chronic cases there may also be muscle fibre atrophy and}

fibrosis.118 _{Organisms may not be visible within myofibres, and definitive diagnosis can}

require the use of immunohistochemistry (IHC), serology and PCR. Overseas, other protozoal organisms including Leishmania infantum and Hepatozoon americanum, as well as the rickettsial organism Ehrlichia canis, can cause myositis or muscle atrophy in dogs, often in addition to more generalised clinical signs.152 _{These organisms, as well as}

the tick vectors of H. canis and E. canis, are currently exotic to New Zealand.153

Trichinella spiralis is a nematode parasite that can cause muscle damage in animals

and humans. Infection in people is usually associated with under-cooked pork products, and although the organism is considered endemic in New Zealand, the reported prevalence in wild pigs is very low and clinical cases are rarely reported in humans.154-156 _{The last confirmed finding of T. spiralis in pigs in New Zealand was in a}

single pig in 2007,154 _{and extensive monitoring programs since 1969 (testing both}

commercially farmed and wild pig meat) have not detected any infected pigs.156

Animals are infected with Trichinella after eating larvae encysted in muscle, and digestive enzymes release the larvae within the small intestine. Adult worms develop within the intestinal mucosa and mate to produce larvae, which encyst within striated muscle. In people, invasion of muscle causes myalgia and weakness, with a peripheral eosinophilia.141 _{Dogs are considered relatively resistant to infection and experimental}

dosing of dogs with large numbers of larvae (500 – 5,000) resulted in only mild vomiting and diarrhoea, with no significant increases in serum creatine kinase activity.157 _{In New Zealand, a case of myostitis with peripheral eosinophilia in a}

working farm dog fed raw wild pig meat and horse meat was investigated in 2013, but

Trichinella was ruled out as a cause using serum ELISA and western blot tests.158

Overseas, there has been a case report of Trichinella causing clinical signs of

neuromuscular disease, primarily muscle weakness, in a dog, and in this case larvae were observed histologically in muscle, surrounded by a thick hyaline capsule.119 _This

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and macrophages, variability in myofibre size, and evidence of muscle regeneration and atrophy. Hunting dogs might be more likely than other dogs to be exposed to

Trichinella spp. due to opportunities they might have to consume wild pig tissues, and

hunting dogs have been used as sentinels for monitoring Trichinella spp. in wildlife.159

1.4.3.3 Fungal and viral myositis in dogs

In humans, fungal causes of myositis (including Aspergillusspp. Blastomyces

dermatitidis, Candida spp., Coccidioides spp., Cryptococcus neoformans, Fusarium spp., Histoplasma capsulatum and Pneumocystis jiroveci) have been documented but are

considered rare.141 _{A study of 200 cases of inflammatory cases in dogs did not include}

any cases of fungal myositis, and serology for various fungal organisms in seven of these dogs was negative.160 _{The author of this thesis has personally diagnosed a case}

of systemic cryptococcosis in a pig hunting dog in New Zealand that presented with progressive lethargy, weight loss and a poor hair coat. In this case, yeast organisms were visible in multiple organs, including the liver and skeletal muscle (Figure 1.3), but were not associated with any significant muscle degeneration or inflammation. There are no reports of viral-induced myopathies or viral myositis in dogs in New Zealand.152

Figure 1.3: Skeletal muscle histology of a dog with systemic cryptococcosis (HE) at 200x (L) and

400x magnification (R). Basophilic, round 5 - 10μm diameter yeasts are surrounded by thick, non-staining capsules. Adjacent skeletal muscle fibres are normal and there is no

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1.4.3.4 Immune mediated myositis in dogs

Immune-mediated myositis has been reported in dogs, cats and horses and is usually characterised histologically by lymphocytic invasion of myofibres and perivascular lymphocytic inflammation.120 _{Immune-mediated myopathies in dogs may be}

generalised or only affect focal muscle groups, such as masticatory muscle myositis and extraocular myositis. Polymyositis is a generalised immune-mediated muscle disease characterised clinically by muscle pain, weakness, a stilted gait and pyrexia.161

Affected dogs have high serum muscle enzyme activities, electromyographic

abnormalities, lymphocytic infiltrates in skeletal muscle, and are negative on serology for infectious diseases known to cause muscle damage. In masticatory muscle myositis, lesions are restricted to muscles innervated by the mandibular branch of the

trigeminal nerve and result in jaw pain, inability to open the mouth and masticatory muscle atrophy.160 _{Immune complex deposition in this disease is limited to type 2M}

muscle fibres, which are only found in masticatory muscles and are distinct from the fibre types in limb muscles.162 _{Extraocular myositis results in bilateral exophthalmos}

without protrusion of the third eyelid.163 _{The disease is rare and poorly characterised,}

but is most commonly reported in young, entire female Golden Retrievers and cases respond well to systemic corticosteroids at anti-inflammatory doses.